Methods for treating chronic inflammatory demyelinating polyneuropathy

Abstract

The present invention relates to a method for treating chronic inflammatory demyelinating polyneuropathy (CIDP) using a human neonatal Fc receptor (FcRn) antagonist, in a particular embodiment, the human neonatal Fc receptor (FcRn) antagonist being efgaltigimod.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims the benefits and priority of UK Patent Application No. 2310890.5 filed on 16 July 2023, U.S. Provisional Patent Application No. 63 / 617,702 filed on 4 January 2024, and U.S. Provisional Patent Application No. 63 / 662,098 filed on 20 June 2024, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to a method for treating chronic inflammatory demyelinating polyneuropathy (CIDP) using a human neonatal Fc receptor (FcRn) antagonist, in a particular embodiment, the human neonatal Fc receptor (FcRn) antagonist being efgaltigimod. [Background technology]

[0003] CIDP is the most common chronic immune-mediated inflammatory polyneuropathy, with an estimated incidence of approximately 0.8–8.9 cases per 100,000 people (Lehmann et al., 2019). The prevalence of CIDP increases with age, with an average age of onset of 48 years. CIDP primarily affects men, with a male-to-female ratio of approximately 2:1 (Vallat et al., 2010).

[0004] CIDP is a symmetrical sensorimotor disorder characterized by cytoalbuminological dissociation and interstitial and periendoneural infiltration by lymphocytes and macrophages. Clinically, CIDP most commonly presents with an insidious onset, either with a chronic progressive or relapsing course.

[0005] CIDP is a highly heterogeneous condition. Multiple variants of CIDP have been described that share common immunological or inflammatory manifestations, as well as electrophysiological and / or pathological evidence of demyelinating neuritis. There is no consensus on the best approach for the nomenclature of these disorders. CIDP variants include those with primarily sensory symptoms, distal symmetrical disorders or distal acquired demyelinating symmetrical neuritis (DADS), multifocal acquired demyelinating sensory and motor neuritis (MADSAM), and CIDP with associated central nervous system (CNS) demyelination or other systemic disorders (Lehmann et al., 2019). As a result of the heterogeneity present in the indications for this disease, diagnosis is extremely difficult, and misdiagnosis is common (Van den Bergh et al., 2021).

[0006] The underlying pathogenesis of CIDP is not well understood. The enduring theory is that cellular immune mechanisms, along with humoral mechanisms, act synergistically to cause peripheral nerve damage. CIDP nerve biopsies are performed using CD8 + T cells, CD4 + The study revealed infiltration of inflammatory cells, including T cells and macrophages. While antibodies against myelin protein and nodal antigen were detected, direct evidence of pathogenic antibodies in the broad CIDP population is limited. The heterogeneity in CIDP is thought to reflect different immunological mechanisms at work in patients with this condition (Mathey et al., 2015).

[0007] For patients with CIDP, the most common treatments currently are immunosuppressive or immunomodulatory interventions. Intravenous immunoglobulin (IVIg) is typically the first-line treatment for most patients. IVIg is a relatively nonspecific form of therapy that may mediate its therapeutic effect through multiple modes of action. In the treatment of CIDP, the therapeutic effect of IVIg is thought to be mediated through a combination of the following: (i) anti-idiotype antibody activity, (ii) saturation of FcRn, (iii) anti-complement activity, (iv) upmodulation of inhibitory FcγRIIb receptors that inhibit macrophage activation, and (v) downmodulation of costimulatory and adhesion molecules (Dalakas et al., 2022). The relative importance of these mechanisms is largely unknown. IVIg is usually administered at a high dose, followed by maintenance doses every 2–6 weeks (Bunschoten et al., 2019). This dosing regimen suggests a more indirect mechanism of action of IVIg in the treatment of CIDP.

[0008] Other commonly used therapeutic agents include subcutaneous immunoglobulin (SCIg), corticosteroids, plasma separation, plasma exchange, prednisone, azathioprine, methotrexate, mycophenolate, cyclosporine, and cyclophosphamide.

[0009] Despite available treatments, a significant number of patients experience continued disease progression in the form of relapses or progressive impairment. In the case of IVIg / SCIg, infusions require hospital visits and long-term treatment, which is often expensive. Corticosteroids are often more cost-effective but are associated with adverse side effects (Kuwabara et al., 2006). Therefore, there is an unmet medical need for new and effective treatments for CIDP. [Overview of the Initiative]

[0010] The clinical trial results presented herein establish for the first time the efficacy of FcRn antagonists in the treatment of CIDP. As described above, to date there has been no consensus on the underlying pathology of CIDP. In fact, CIDP has long been recognized as a highly heterogeneous condition. Relatively nonspecific immunosuppressive therapies, particularly treatment with IVIg, are considered beneficial in CIDP by many experts in the field due to the multiple modes of action of such therapies (Dalakas et al., 2022). The data reported herein demonstrate that the FcRn antagonist efgaltigimod is also effective in improving symptoms in patients with CIDP and preventing relapses after symptom improvement. These effects were observed across a broad population of CIDP patients with diverse baseline characteristics. These results establish for the first time that blocking FcRn activity with the use of an FcRn antagonist is an effective therapeutic approach for the treatment of CIDP.

[0011] Accordingly, in a first aspect, the present invention provides a method for treating CIDP in a subject requiring treatment of CIDP, the method comprising administering to the subject an effective amount of an FcRn antagonist. Also included in this first aspect is an FcRn antagonist for use in the treatment of CIDP, according to any of the methods described herein. Also included in this first aspect is the use of an FcRn antagonist in the manufacture of a pharmacopoeia for the treatment of CIDP, wherein the treatment is carried out according to any of the methods disclosed herein.

[0012] In some embodiments, the FcRn antagonist includes two, three, or four FcRn binding regions.

[0013] In some embodiments, the FcRn antagonist includes or consists of a variant Fc region or its FcRn-binding fragment. In some embodiments, the variant Fc region or its FcRn-binding fragment binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region. Alternatively or additionally, the variant Fc region or its FcRn-binding fragment binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

[0014] In some embodiments, the variant Fc region includes or consists of a first Fc domain and a second Fc domain that form a homodimer or heterodimer. In some embodiments, the first Fc domain and / or the second Fc domain contain amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, 434, and 436, respectively. In some embodiments, the first Fc domain and / or the second Fc domain contain amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0015] In some embodiments, the first Fc domain and / or the second Fc domain include an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

[0016] In some embodiments, the FcRn antagonist is Evgarchigimodo.

[0017] In some embodiments, the FcRn antagonist is an anti-FcRn antibody.

[0018] In some embodiments, the FcRn antagonist is administered to a subject at a fixed dose of 200 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered to a subject at a dose of 2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered to a subject at a fixed dose of about 800 to about 1200 mg. In some embodiments, the FcRn antagonist is administered to a subject at a fixed dose of about 1000 mg.

[0019] In some embodiments, the FcRn antagonist is administered subcutaneously.

[0020] In some embodiments, the FcRn antagonist is administered to a subject once a week. In some embodiments, the FcRn antagonist is administered to a subject once every two weeks. In some embodiments, the FcRn antagonist is administered to a subject once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0021] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1000 mg.

[0022] In some embodiments, the FcRn antagonist is administered during an induction period followed by a maintenance period. The FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1000 mg during the induction period, and the FcRn antagonist is administered subcutaneously once every two weeks at a fixed dose of about 1000 mg during the maintenance period.

[0023] In some embodiments, the FcRn antagonist is first administered subcutaneously once a week at a fixed dose of about 1000 mg, and then subcutaneously once every two weeks at a fixed dose of about 1000 mg based on clinical evaluation. In some embodiments, the once-a-week subcutaneous administration at a fixed dose of about 1000 mg is resumed in response to worsening of symptoms.

[0024] In some embodiments, the FcRn antagonist is administered intravenously. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered at a dose of about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 5 mg / kg, 10 mg / kg, or 25 mg / kg.

[0025] In some embodiments, the FcRn antagonist is first administered intravenously and then subcutaneously.

[0026] In some embodiments, the FcRn antagonist is administered for 61 weeks or less, 52 weeks or less, or 48 weeks or less. In some embodiments, the FcRn antagonist is administered for at least 12 weeks.

[0027] In some embodiments, the FcRn antagonist is administered subcutaneously once a week for at least four weeks. In some embodiments, the FcRn antagonist is administered subcutaneously once a week until the subject shows evidence of clinical improvement (ECI). In some embodiments, the FcRn antagonist is administered subcutaneously once a week until the subject shows ECI during two consecutive measurements. In some embodiments, the FcRn antagonist is administered subcutaneously once a week until the subject shows two ECIs in two weeks. In some embodiments, ECI is a clinical improvement in one or more of the following: Inflammatory Rasch-built Overall Disability Scale (I-RODS), mean grip strength, or Inflammatory Neuropathy Cause and Treatment (INCAT) score. In some embodiments, an FcRn antagonist is administered subcutaneously once a week until the subject shows evidence of clinically significant progression (ECMD). In some embodiments, ECMD is one or more of the following: an increase of 1 or more points in the adjusted INCAT (aINCAT) score, a decrease of 4 or more points in I-RODS (using centile metrics), or a decrease of 8 kPa or more in average grip strength in one hand using a handheld dynamometer. In some embodiments, ECMD is an increase of 1 or more points in the aINCAT score, optionally an increase of 1 or more points in the aINCAT score during two consecutive measurements, optionally an increase of 1 or more points in the aINCAT score during two weeks. In some embodiments, ECMD is an increase of 2 or more points in the aINCAT score.

[0028] In some embodiments, the subjects are diagnosed with CIDP according to the EFNS / PNS2010 diagnostic criteria. In some embodiments, the subjects have typical CIDP. In some embodiments, the subjects have a CIDP variant, which is optionally selected from distal CIDP, multifocal CIDP, focal CIDP, motor CIDP, and sensory CIDP.

[0029] In some embodiments, the subjects have progressive or recurrent CIDP.

[0030] In some embodiments, subjects have an aINCAT score of 2 or higher, optionally 3 or higher, optionally 4 or higher, or optionally 5 or higher before administration of an FcRn antagonist.

[0031] In some embodiments, subjects have an I-RODS centile metric score of 10 or higher, optionally 20 or higher, optionally 30 or higher, optionally 40 or higher, or optionally 50 or higher before administration of an FcRn antagonist.

[0032] In some embodiments, the subjects have been newly diagnosed with CIDP. In some embodiments, the subjects are treatment-naïve for CIDP. In some embodiments, the subjects have previously received treatment for CIDP, optionally steroid therapy, optionally IVIg or SCIg therapy. In some embodiments, the subjects have previously received treatment for CIDP, optionally steroid therapy, optionally IVIg or SCIg therapy, but have not received treatment for CIDP in the six months prior to the initiation of FcRn antagonist treatment. In some embodiments, the subjects have active disease despite treatment with corticosteroids or immunoglobulins.

[0033] In some embodiments, the subjects are CIDP patients characterized by the presence of autoantibodies, such as anti-NF155 antibody, anti-CNTN1 antibody, anti-Caspr1 antibody, anti-NF140 / 186 antibody, anti-GM-1 antibody, and / or anti-LM-1 antibody.

[0034] In some embodiments, control of disease activity, partial remission, or complete remission is achieved after administration of an FcRn antagonist. In some embodiments, control of disease activity, partial remission, or complete remission is achieved within 12 weeks, optionally within 8 weeks, optionally within 6 weeks, optionally within 4 weeks, or optionally within 3 weeks of initial FcRn antagonist administration. In some embodiments, control of disease activity, partial remission, or complete remission persists in the subject for at least 2 months or at least 6 months.

[0035] In some embodiments, once control of disease activity, partial remission, or complete remission is achieved, continued administration of an FcRn antagonist prevents symptom exacerbations. The absence of symptom exacerbations may be measured using one of the following: INCAT score, Medical Research Council (MRC) total score, I-RODS, mean grip strength test, or Timed Up and Go (TUG) test.

[0036] In some embodiments, the treatment prevents or delays relapse. In some embodiments, the treatment prevents or delays relapse for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks.

[0037] In some embodiments, the treatment prevents or delays relapse during the duration of treatment with an FcRn antagonist.

[0038] In some embodiments, the treatment prevents or delays relapse after discontinuation of treatment with an FcRn antagonist. In some embodiments, the treatment prevents or delays relapse after discontinuation of treatment for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks. In some embodiments, the treatment reduces the risk of relapse by at least 60%.

[0039] In some embodiments, subjects show improvement in symptoms after administration of an FcRn antagonist, as measured using the INCAT score, preferably the aINCAT score. In some embodiments, subjects show a decrease of 1 or more points, optionally 2 or more points, in the aINCAT score.

[0040] In some embodiments, subjects show improvement in symptoms after administration of an FcRn antagonist, as measured using the total MRC score.

[0041] In some embodiments, subjects show improvement in symptoms after administration of an FcRn antagonist, as measured using I-RODS. In some embodiments, subjects show an increase of 4 points or more in the I-RODS centile metric score.

[0042] In some embodiments, subjects show improvement in symptoms after administration of an FcRn antagonist, as measured using an average grip strength test. In some embodiments, subjects show an increase in average grip strength of 8 kPa or more.

[0043] In some embodiments, subjects show improvement in symptoms after administration of an FcRn antagonist, as measured using the TUG test.

[0044] In some embodiments, symptom improvement is achieved within 12 weeks, optionally within 8 weeks, optionally within 6 weeks, optionally within 4 weeks, or optionally within 3 weeks of initial FcRn antagonist treatment.

[0045] In some embodiments, subjects show a decrease in serum levels of total IgG, autoantibodies, cytokines / chemokines, or immune complexes after administration of an FcRn antagonist. In some embodiments, serum levels of total IgG, autoantibodies, cytokines / chemokines, or immune complexes are measured 4, 12, 24, or 48 weeks after administration of the FcRn antagonist. In some embodiments, subjects show a decrease in serum levels of one or more autoantibodies selected from the group consisting of anti-GM1, anti-LM-1, anti-NF-155, anti-CNTN1, anti-Caspr-1 antibodies, and anti-myelinating neuronal antibodies after administration of an FcRn antagonist.

[0046] In some embodiments, subjects do not show a decrease in serum albumin levels after administration of an FcRn antagonist. In some embodiments, subjects do not show an increase in serum cholesterol after administration of an FcRn antagonist.

[0047] In some embodiments, the subject exhibits an ECI (End-Case Infection) after first receiving an FcRn antagonist. In some embodiments, the subject exhibits an ECI within 31 to 51 days after first receiving an FcRn antagonist. In some embodiments, the subject exhibits an ECI within 43 days after first receiving an FcRn antagonist.

[0048] In some embodiments, the method further comprises administering to the subject an effective amount of one or more additional therapeutic agents, optionally corticosteroids.

[0049] In some embodiments, the method is used to assist in the diagnosis of CIDP.

[0050] In another embodiment, a method is provided for treating CIDP in a patient population, comprising administering 1008 mg / 11,200 units of efgartigimod PH20 or a biosimilar version thereof once weekly, wherein 66.5% of the patient population exhibits an ECI after administration of efgartigimod PH20 or a biosimilar version thereof.

[0051] In some embodiments, the patient population achieves ECI within 31–51 days of first receiving efgartigimod PH20 or its biosimilar version. In some embodiments, the patient population achieves ECI within 43 days of first receiving efgartigimod PH20 or its biosimilar version.

[0052] In some embodiments, the patient population includes 322 subjects.

[0053] In some embodiments, anti-evgultigimod alpha antibodies are detected in 6% of the patient population after administration of efgultigimod PH20 for up to 12 weeks. In some embodiments, neutralizing anti-evgultigimod alpha antibodies are detected in 0.3% of the patient population after administration of efgultigimod PH20 for up to 12 weeks.

[0054] In some embodiments, subjects in the patient population remain recurrence-free for significantly longer than subjects who did not receive efgaltigimod PH20 or its biosimilar version.

[0055] In some embodiments, subjects in the patient population experienced a longer time to clinical exacerbation compared to subjects who did not receive efgaltigimod PH20 or its biosimilar version, with clinical exacerbation being an increase of 1 or more points in the aINCAT score. In some embodiments, clinical exacerbation was an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation was an increase of 2 or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation was indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation was statistically significant.

[0056] In some embodiments, subjects in patient populations treated with efgaltigimod PH20 or its biosimilar version showed a 61% reduction in the risk of exacerbation in patients with CIDP.

[0057] In another embodiment, a method for treating CIDP in a subject is provided herein, comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once weekly, wherein the subject exhibits ECI after administration of efgultigimod PH20 or a biosimilar version thereof. In some embodiments, the subject achieves ECI within 31 to 51 days after first receiving efgultigimod PH20 or a biosimilar version thereof. In some embodiments, the subject achieves ECI within 43 days after first receiving efgultigimod PH20 or a biosimilar version thereof. In some embodiments, the subject remains relapse-free for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks after administration of efgultigimod PH20 or a biosimilar version thereof. In some embodiments, the subject exhibits a reduced risk of exhibiting ECMD. In some embodiments, ECMD is an increase of one or more aINCAT score, optionally an increase of one or more aINCAT score during two consecutive measurements, or optionally an increase of one or more aINCAT score during two weeks. In some embodiments, ECMD is an increase of two or more aINCAT score.

[0058] In another embodiment, a method for treating CIDP in a patient population is provided herein, comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once weekly, wherein the mean percentage reduction in total IgG levels from baseline in the patient population after administration of efgultigimod PH20 or a biosimilar version ranged from 66.8% to 71.6%. In some embodiments, the mean percentage reduction in total IgG levels from baseline ranged from 66.8% to 71.6% in the patient population after a total of four weekly administrations of efgultigimod PH20 or a biosimilar version thereof. In some embodiments, the mean percentage reduction in total IgG levels from baseline persisted from week 4 throughout the treatment period. In some embodiments, the patient population included 322 subjects.

[0059] In another embodiment, a method for treating CIDP in a subject is provided herein, comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once weekly, such that the subject exhibits a 66.8%–71.6% decrease in serum total IgG levels after administration of efgultigimod PH20 or a biosimilar version compared to baseline levels prior to administration of efgultigimod PH20 or a biosimilar version. In some embodiments, the subject exhibits a 66.8%–71.6% decrease in serum total IgG levels after a total of four weekly administrations of efgultigimod PH20 or a biosimilar version. In some embodiments, the decrease in serum total IgG levels persists until the once-weekly administration of efgultigimod PH20 or a biosimilar version is discontinued.

[0060] In another embodiment, a method for treating CIDP in subjects in a patient population is provided herein, comprising administering 1008 mg / 11,200 units of efgartigimod PH20 or a biosimilar version thereof once weekly, wherein subjects in the patient population experience a longer time to clinical exacerbation compared to subjects who do not receive efgartigimod PH20 or a biosimilar version thereof, and this is statistically significant, with clinical exacerbation being an increase of 1 point or more in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the patient population includes 221 subjects.

[0061] In another embodiment, the Specified Method of Treating CIDP in a Subject Requiring Treatment of CIDP is provided herein, the Method comprising subcutaneously administering to the subject a clinically safe and effective dose of efgaltigimod PH20 once weekly.

[0062] In some embodiments, a clinically proven safe and effective dose of efgartigimod PH20 is administered subcutaneously over approximately 30 to 90 seconds. In some embodiments, a clinically proven safe and effective dose of efgartigimod PH20 is 1008 mg / 11,200 units.

[0063] In some embodiments, subjects show evidence of improvement after administration of efgultigimod PH20. In some embodiments, subjects show evidence of improvement during two consecutive measurements. In some embodiments, evidence of improvement is selected from an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

[0064] In some embodiments, subjects experience a longer time to clinical exacerbation after administration of efgartigimod PH20 compared to subjects who do not receive efgartigimod PH20. In some embodiments, the longer time to clinical exacerbation is statistically significant. In some embodiments, clinical exacerbation is defined as an increase of 1 or more aINCAT score, an optional increase of 1 or more aINCAT score during two consecutive measurements, or an optional increase of 1 or more aINCAT score during two weeks. In some embodiments, clinical exacerbation is defined as an increase of 2 or more aINCAT score.

[0065] In another embodiment, a method for treating CIDP in a patient population is provided herein, the method comprising subcutaneous administration of a clinically proven safe and effective dose of efgaltigimod PH20 once weekly.

[0066] In some embodiments, a clinically proven safe and effective dose of efgartigimod PH20 is administered subcutaneously over approximately 30 to 90 seconds. In some embodiments, a clinically proven safe and effective dose of efgartigimod PH20 is 1008 mg / 11,200 units.

[0067] In some embodiments, the patient population shows evidence of improvement in 69% of subjects in the patient population after administration of efgaltigimod PH20 during two consecutive measurements. In some embodiments, evidence of improvement is selected from an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

[0068] In some embodiments, subjects in the patient population experience a longer time to clinical exacerbation compared to subjects who did not receive efgaltigimod PH20 or its biosimilar version, with clinical exacerbation being an increase of 1 or more points in the aINCAT score. In some embodiments, clinical exacerbation is an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation is an increase of 2 or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant. In some embodiments, the patient population includes 221 subjects.

[0069] In another embodiment, fgultigimod PH20 for use in the treatment of CIDP in subjects requiring treatment of CIDP is provided herein, wherein a clinically safe and effective dose of fgultigimod PH20 is administered subcutaneously to the subject once a week or once every two weeks. In some embodiments, a clinically safe and effective dose of fgultigimod PH20 is administered subcutaneously once a week.

[0070] In some embodiments, a clinically proven safe and effective dose of efgaltigimod PH20 is initially administered subcutaneously once a week, and then, based on clinical evaluation, subcutaneously once every two weeks. In some embodiments, weekly subcutaneous administration is resumed in response to symptom exacerbation.

[0071] In some embodiments, clinically proven safe and effective doses of efgaltigimod PH20 are administered subcutaneously over approximately 30 to 90 seconds.

[0072] In some embodiments, a clinically proven safe and effective dose of efgultigimod PH20 contains 1000 mg of efgultigimod alpha.

[0073] In some embodiments, the subjects have an active disease despite treatment with corticosteroids or immunoglobulins.

[0074] In some embodiments, the subjects have received prior CIDP therapy prior to the initiation of efgultigimod PH20 treatment, and efgultigimod PH20 is administered before the clinical effect of the prior CIDP therapy diminishes. In some embodiments, the prior CIDP therapy is a corticosteroid or immunoglobulin.

[0075] In some embodiments, subjects show a 66.8%–71.6% decrease in serum total IgG levels after administration of efgultigimod PH20 compared to baseline levels before administration of efgultigimod PH20. In some embodiments, subjects show a 66.8%–71.6% decrease in serum total IgG levels after four weekly administrations of efgultigimod PH20. In some embodiments, the decrease in serum total IgG levels persists until weekly administration of efgultigimod PH20 is discontinued.

[0076] In some embodiments, when efgartigimod PH20 is administered to a patient population with CIDP, it induces an ECI response in 66.5% of the target population.

[0077] In some embodiments, subjects exhibit an endocrine response (ECI) after administration of efgultigimod PH20. In some embodiments, subjects exhibit an ECI within 31 to 51 days of initial efgultigimod PH20 administration. In some embodiments, subjects exhibit an ECI within 43 days of initial efgultigimod PH20 administration.

[0078] In some embodiments, subjects remained relapse-free for a significantly longer period after administration of efgultigimod PH20 compared to subjects who did not receive efgultigimod PH20.

[0079] In some embodiments, subjects demonstrate a reduced risk of showing evidence of clinical exacerbation after administration of efgaltigimod PH20. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score during two weeks. In some embodiments, evidence of clinical exacerbation is an increase of 2 or more points in the aINCAT score.

[0080] In another embodiment, fgultigimod PH20 for use in the treatment of CIDP in a patient population, wherein the treatment comprises subcutaneous administration of a clinically safe and effective dose of fgultigimod PH20 once weekly or once every two weeks. In some embodiments, a clinically safe and effective dose of fgultigimod PH20 is administered subcutaneously once weekly. In some embodiments, a clinically safe and effective dose of fgultigimod PH20 is initially administered subcutaneously once weekly, and then, based on clinical evaluation, subcutaneously once every two weeks. In some embodiments, the once-weekly subcutaneous administration is resumed in response to symptom exacerbation.

[0081] In some embodiments, clinically proven safe and effective doses of efgaltigimod PH20 are administered subcutaneously over approximately 30 to 90 seconds.

[0082] In some embodiments, a clinically proven safe and effective dose of efgultigimod PH20 contains 1000 mg of efgultigimod alpha.

[0083] In some embodiments, subjects in the patient population have an active disease despite treatment with corticosteroids or immunoglobulins.

[0084] In some embodiments, subjects in the patient population have received prior CIDP therapy prior to the initiation of efgartigimod PH20 treatment, and efgartigimod PH20 is administered before the clinical effect of the prior CIDP therapy diminishes. In some embodiments, the prior CIDP therapy is corticosteroids or immunoglobulins.

[0085] In some embodiments, the mean percentage reduction in total IgG levels from baseline ranged from 66.8% to 71.6% in the patient population after administration of efgaltigimod PH20. In some embodiments, the mean percentage reduction in total IgG levels from baseline ranged from 66.8% to 71.6% in the patient population after four weekly administrations of efgaltigimod PH20. In some embodiments, the mean percentage reduction in total IgG levels from baseline persisted from week 4 throughout the treatment period.

[0086] In some embodiments, the patient population exhibits ECI in 66.5% of the subjects after administration of efgaltigimod PH20. In some embodiments, the patient population achieves ECI within 31 to 51 days after initial administration of efgaltigimod PH20. In some embodiments, the patient population achieves ECI within 43 days after initial administration of efgaltigimod PH20.

[0087] In some embodiments, the subjects in the patient population remained recurrence-free for a significantly longer period than those who did not receive efgaltigimod PH20.

[0088] In some embodiments, subjects in patient populations treated with efgaltigimod PH20 showed a 61% reduction in the risk of exacerbation.

[0089] In some embodiments, the patient population exhibits a reduced risk of showing evidence of clinical exacerbation after administration of efgaltigimod PH20. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, evidence of clinical exacerbation is an increase of 1 or more points in the aINCAT score during two weeks. In some embodiments, evidence of clinical exacerbation is an increase of 2 or more points in the aINCAT score.

[0090] In some embodiments, the patient population includes 322 subjects.

[0091] In some embodiments, the subjects in any of the methods or uses described herein are adults.

[0092] In another embodiment, a pharmaceutical product approved for the treatment of CIDP comprising efgultigimod and hyaluronidase is provided herein, wherein the pharmaceutical product is formulated for subcutaneous administration. In some embodiments, the pharmaceutical product is formulated for subcutaneous administration over a period of approximately 30 to 90 seconds. In some embodiments, the pharmaceutical product is administered in a total volume of 5.6 mL.

[0093] In some embodiments, the pharmaceutical product is provided in a single-dose vial at a concentration of 180 mg efgultigimod / 2000 units hyaluronidase per mL. In some embodiments, the pharmaceutical product is provided in a single-dose vial containing 180 mg / mL efgultigimod, 2000 units / mL recombinant human hyaluronidase (rHuPH20), 1.4 mg / mL histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL methionine, 0.4 mg / mL polysorbate 20, 5.8 mg / mL sodium chloride, 20.5 mg / mL sucrose, and water for injection, USP, in a total volume of 5.6 mL at pH 6.0.

[0094] In some embodiments, the drug is a reference described based on efgultigimod administered at a dose of 1000 mg. In some embodiments, the drug is a reference described based on efgultigimod administered at a dose of 1008 mg. In some embodiments, the drug is a reference described based on hyaluronidase administered at a dose of 11,200 units.

[0095] In some embodiments, the drug is a reference described based on administration once a week or once every two weeks. In some embodiments, the drug is a reference described based on administration once a week. In some embodiments, the drug is a reference described based on administration once a week, followed by adjustment to administration once every two weeks based on clinical evaluation. In some embodiments, the drug is a reference described based on resumption of administration once a week in case of symptom exacerbation.

[0096] In some embodiments, the drug is approved for administration to adult patients. In some embodiments, the drug has an approved indication for the treatment of CIDP in adult patients with active disease despite treatment with corticosteroids or immunoglobulins.

[0097] In some embodiments, the pharmaceutical product is contraindicated in patients with severe hypersensitivity to the fgultigimod alfa product, to hyaluronidase, or to any excipient of the pharmaceutical product.

[0098] In some embodiments, the drug induces improvement in 69% of a group of CIDP patients who receive 1008 mg / 11,200 units of efgaltigimod PH20 once a week for up to 12 weeks, within two consecutive visits. In some embodiments, improvement is an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

[0099] In some embodiments, the drug induced an ECI response in 66.5% of a population of CIDP patients receiving 1008 mg / 11,200 units of efgaltigimod PH20 once weekly. In some embodiments, the median time to the first confirmed ECI in the CIDP patient population was 43 days from the first dose of the drug. In some embodiments, up to 40% of CIDP patients in the CIDP patient population had an ECI response within 4 weeks from the first dose of the drug. In some embodiments, 25% of CIDP patients in the CIDP patient population showed a clinically relevant improvement in at least one of the following: aINCAT score, I-RODS, or mean grip strength, within 9 days of the first dose of the drug. In some embodiments, the CIDP patient population included 322 CIDP patients. In some embodiments, CIDP patients in the CIDP patient population who received the drug remained relapse-free for significantly longer than CIDP patients in the CIDP patient population who received placebo. In some embodiments, CIDP patients in the group receiving the medication showed a 61% reduction in the risk of exacerbation compared to CIDP patients in the group receiving placebo.

[0100] In some embodiments, CIDP patients in a population of CIDP patients experience a longer time to clinical exacerbation compared to CIDP patients in a population of CIDP patients receiving placebo. In some embodiments, clinical exacerbation is defined as an increase of one or more points in the aINCAT score. In some embodiments, clinical exacerbation is defined as an increase of one or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation is defined as an increase of two or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant.

[0101] In some embodiments, the drug induces a hypersensitivity reaction selected from the group consisting of anaphylaxis and hypotension causing syncope. In some embodiments, the hypotension causing anaphylaxis or syncope occurs during or within one hour after administration of the drug.

[0102] In some embodiments, the drug induces an infusion-related reaction. In some embodiments, the infusion-related reaction includes one or more of the following: hypertension, chills, shivering, chest pain, abdominal pain, and back pain. In some embodiments, the infusion-related reaction occurs during or within one hour after administration of the drug. In some embodiments, if a mild to moderate infusion-related reaction occurs during administration of the drug, one or more subsequent doses of the drug are administered with close clinical observation, a slower infusion rate, and prior medication.

[0103] In some embodiments, the drug induces anti-efgultigimod antibodies in 2% of subjects in a population of 117 CIDP patients after treatment with the drug. In some embodiments, the drug induces anti-efgultigimod antibodies in 6% of subjects in a population of 317 CIDP patients after treatment with the drug. In some embodiments, the drug induces neutralizing anti-efgultigimod antibodies in 0.3% of subjects in a population of 317 CIDP patients after treatment with the drug.

[0104] Furthermore, biosimilars of the pharmaceuticals described above and in this specification are provided.

[0105] Furthermore, biological products that are bioequivalent to the pharmaceuticals described above and herein are provided.

[0106] In another embodiment, a kit is provided herein that includes any pharmaceutical product described above and herein, any biosimilar described above and herein, or any biological product described above and herein, as well as a label including an indication for the treatment of CIDP in adult patients.

[0107] In some embodiments, the labeling includes a contraindication in patients with severe hypersensitivity to the fgultigimod alfa product, hyaluronidase, or any excipients in their formulations. In some embodiments, the labeling includes a warning for hypersensitivity reactions selected from anaphylaxis and hypotension causing syncope. In some embodiments, the labeling indicates discontinuation of infusion if anaphylaxis or hypotension causing syncope occurs during or within one hour of administration of the product. In some embodiments, the labeling includes a warning for infusion-related reactions selected from hypertension, chills, shivering, chest pain, abdominal pain, and back pain. In some embodiments, the labeling indicates initiating appropriate treatment if a severe infusion-related reaction occurs during administration of the product. In some embodiments, the labeling indicates that if a mild to moderate infusion-related reaction occurs during administration of the product, the patient may be re-challenged with close clinical observation, a slower infusion rate, and pre-medication.

[0108] In some embodiments, labeling includes data showing improvement over two consecutive visits in 69% of a population of CIDP patients who received 1008 mg / 11,200 units of efgaltigimod PH20 once a week for up to 12 weeks. In some embodiments, improvement is an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

[0109] In some embodiments, the labeling includes data showing an ECI response in 66.5% of a population of CIDP patients who received 1008 mg / 11,200 units of efgaltigimod PH20 once weekly. In some embodiments, the labeling includes data showing that the median time to the first confirmed ECI in the population of CIDP patients was 43 days from the first dose of efgaltigimod PH20. In some embodiments, the labeling indicates that up to 40% of patients had an ECI at week 4, which is the earliest point in time when the ECI criteria can be met. In some embodiments, the labeling indicates that 25% of patients showed a clinically relevant improvement after 9 days in at least one of three parameters (aINCAT, I-RODS, or grip strength). In some embodiments, the labeling includes data showing that CIDP patients in the population of CIDP patients who received efgaltigimod PH20 remained relapse-free for significantly longer than CIDP patients in the population of CIDP patients who received placebo. In some embodiments, the labeling includes data showing CIDP patients in a population of CIDP patients who received efgartigimod PH20, indicating a 61% reduction in the risk of exacerbation compared to CIDP patients in a population of CIDP patients who received placebo. In some embodiments, the labeling includes data showing that CIDP patients who received efgartigimod PH20 experienced a longer time to clinical exacerbation (i.e., an increase of 1 or more points in the aINCAT score) compared to CIDP patients in a population of CIDP patients who received placebo. In some embodiments, clinical exacerbation is defined as an increase of 2 or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant.

[0110] In some embodiments, the labeling includes data showing a 2% prevalence of anti-efgartigimod alpha antibody in a population of 117 CIDP patients after treatment with a drug. In some embodiments, the labeling includes data showing a 6% prevalence of anti-efgartigimod alpha antibody in a population of 317 CIDP patients after treatment with a drug. In some embodiments, the labeling includes data showing a 0.3% prevalence of neutralizing anti-efgartigimod alpha antibody in a population of 317 CIDP patients after treatment with a drug.

[0111] In another embodiment, a method for treating CIDP in a subject requiring treatment of CIDP is provided herein, the method comprising administering to the subject any pharmaceutical product, any biosimilar, or any biological product described above and herein. [Brief explanation of the drawing]

[0112] [Figure 1] This is a schematic diagram of a two-part Phase II study to investigate the efficacy, safety, tolerability, immunogenicity, PK, and PD of efgultigimod PH20SC (efgultigimod co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) for subcutaneous (SC) injection) in patients aged 18 years or older with CIDP. d = day, OLE = open-label extension, placebo = placebo with rHuPH20, Q1W = once a week, SC = subcutaneous, w = week.

[0113] [Figure 2] This is a questionnaire used in I-RODS.

[0114] [Figure 3A]Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown. Time to the first aINCAT score progression in the placebo (lower line) and efgaltigimod (upper line) treatment groups. These results are presented for the primary population of the trial, i.e., the mITT analysis set. Kaplan-Meier plot of results. [Figure 3B] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown: time to first aINCAT score progression in the placebo (lower line) and efgaltigimod (upper line) treatment groups. These results are presented for the primary population of the trial, i.e., the mITT analysis set. Calculations of the median time to first aINCAT score progression, as well as the percentage of clinical progressions observed at 24 and 48 weeks during the Stage B trial.

[0115] [Figure 4A] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown. Time to the first aINCAT score progression in the placebo (lower line) and efgaltigimod (upper line) treatment groups. These results are presented for the per-protocol analysis set, i.e., for all patients in the study who fully adhered to the trial protocol. Kaplan-Meier plots of the results. [Figure 4B] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown: time to first aINCAT score progression in the placebo (lower line) and efgaltigimod (upper line) treatment groups. These results are presented for the per-protocol analysis set, i.e., for all patients in the study who fully adhered to the trial protocol. Calculations of the median time to first aINCAT score progression, as well as the percentage of clinical progressions observed at 24 and 48 weeks during the Stage B trial.

[0116] [Figure 5A]Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown: Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Kaplan-Meier analysis of the results. [Figure 5B] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown. Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Calculation of the median time to the first aINCAT score exacerbation. [Figure 5C] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown: Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Kaplan-Meier analysis of the results. [Figure 5D] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown. Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Calculation of the median time to the first aINCAT score exacerbation. [Figure 5E]Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown: Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Kaplan-Meier analysis of the results. [Figure 5F] Results from Stage B of the study, specifically the measurement of the primary endpoint, are shown. Time to the first aINCAT score exacerbation in the placebo (lower line) and efgaltigimod (upper line) treatment groups. Patient groups were stratified according to prior treatment: (i) treatment with corticosteroids (Figures 5A and 5B), (ii) treatment with IVIg or SCIg (Figures 5C and 5D), or treatment-naïve patients (Figures 5E and 5F). Calculation of the median time to the first aINCAT score exacerbation.

[0117] [Figure 6A] Results from Stage B of the study, specifically the measurement of secondary endpoints, are shown: time to CIDP progression in the placebo (lower line) and efgultigimod (upper line) treatment groups. These results are presented for the primary population of the trial, i.e., the mITT analysis set. Time to CIDP disease progression is defined as the time from the first dose of double-blind IMP (placebo or efgultigimod) to a decrease of 4 or more points in the first I-RODS score compared to baseline at Stage B, using the centile metric Cox proportional hazards model. [Figure 6B]Results from Stage B of the study, specifically the measurement of secondary endpoints, are shown: time to CIDP progression in the placebo (lower line) and efgartigimod (upper line) treatment groups. These results are presented for the primary population of the trial, i.e., the mITT analysis set. Time to CIDP disease progression is defined as the time from the first dose of double-blind IMP (placebo or efgartigimod) to a decrease of 4 or more points in the first I-RODS score compared to baseline at Stage B, using centile metrics. Hazard ratio. [Modes for carrying out the invention]

[0118] The present invention relates to a method for treating CIDP. Chronic inflammatory demyelinating polyneuropathy is also referred to in the literature as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The method comprises administering an effective amount of an FcRn antagonist to a subject (e.g., a human subject). The present invention also provides a human FcRn antagonist for use in the treatment of CIDP. Furthermore, the use of an FcRn antagonist in the manufacture of a pharmaceutical for the treatment of CIDP is provided. All embodiments of the present invention described herein are equally applicable to all aspects of the present invention.

[0119] A.Definition Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art of the present invention.

[0120] As used herein, the term "FcRn" refers to the neonatal Fc receptor. An exemplary FcRn molecule is the human FcRn encoded by the FCGRT gene, as shown in RefSeq NM004107. The amino acid sequence of the corresponding protein is shown in RefSeq NP_004098.

[0121] As used herein, the term “FcRn antagonist” refers to any agent that specifically binds to FcRn and inhibits the binding of immunoglobulins to FcRn (e.g., human FcRn). In one embodiment, the FcRn antagonist is an Fc region (e.g., a variant Fc region disclosed herein) that specifically binds to FcRn via an Fc region and inhibits the binding of immunoglobulins to FcRn. In one embodiment, the FcRn antagonist is not a full-length IgG antibody. In one embodiment, the FcRn antagonist comprises an antigen-binding site and a variant Fc region that bind to a target antigen. In one embodiment, the FcRn antagonist is an Fc fragment that contains or consists of an Fc region and lacks an antigen-binding site. In one embodiment, the term "FcRn antagonist" refers to an antibody or its antigen-binding fragment that specifically binds to FcRn via its antigen-binding domain or its Fc region and inhibits the binding of the Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn.

[0122] As used herein, the terms “antibody” and “antibodies” include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules containing antibody CDR, VH, or VL regions. Examples of antibodies include monoclonal antibodies, recombinant antibodies, monospecific antibodies, polyspecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies containing two heavy chains and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-antibody heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single-domain antibodies (sdAb), monovalent antibodies, single-chain antibodies or single-chain Fvs (scFv), camel antibodies, aphibody molecules, humanized antibodies, VHH fragments, Fab fragments, F(ab')2 fragments, disulfide-linked Fv (sdFv), anti-idiotype (anti-Id) antibodies (e.g., anti-anti-Id antibodies), and any of the antigen-binding fragments listed above. Antibodies can be any type of immunoglobulin molecule (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclass (e.g., IgG2a or IgG2b).

[0123] As used herein, the term “Fc domain” refers to a portion of a single immunoglobulin heavy chain that begins in the hinge region of the antibody and terminates at the C-terminus. Thus, a complete Fc domain includes at least a portion of the hinge (e.g., upper, middle, and / or lower hinge regions), the CH2 domain, and the CH3 domain. In some embodiments, the term “Fc domain” refers to a portion of a single immunoglobulin heavy chain that includes both the CH2 and CH3 domains of the antibody. In some embodiments, the Fc domain includes at least a portion of the hinge (e.g., upper, middle, and / or lower hinge regions), the CH2 domain, and the CH3 domain. In some embodiments, the Fc domain does not include the hinge region.

[0124] As used herein, the term “hinge region” refers to the portion of a heavy chain molecule that binds the CH1 domain to the CH2 domain. In some embodiments, the hinge region is up to 70 amino acid residues long. In some embodiments, this hinge region comprises approximately 11 to 17 amino acid residues and is mobile, thus allowing the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region is 12 amino acid residues long. In some embodiments, the hinge region is 15 amino acid residues long. In some embodiments, the hinge region is 62 amino acid residues long. The hinge region can be subdivided into three distinct domains: upper, middle, and lower hinge domains. The FcRn antagonists of this disclosure may include all or any portion of the hinge region. In some embodiments, the hinge region is derived from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence EPKSCDKTHTCPPCP (SEQ ID NO: 31).

[0125] As used herein, the term “Fc region” refers to the portion of an immunoglobulin formed by the Fc domains of its two heavy chains. An Fc region may be a wild-type Fc region (natural Fc region) or a variant Fc region. A natural Fc region is a homodimer. An Fc region may originate from any natural immunoglobulin. In some embodiments, the Fc region is formed from an IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed from an IgG heavy chain constant region. In some embodiments, the IgG heavy chain constant region is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region. In some embodiments, the Fc region is formed from an IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region includes G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotypes (see, for example, Jefferis and Lefranc, 2009 and de Taeye et al., 2020).

[0126] As used herein, the term “variant Fc region” refers to an Fc region having one or more modifications from a native Fc region. Modifications may include amino acid substitutions, additions and / or deletions, linking of additional parts, and / or modifications of the native glycan. This term encompasses each of the constituent Fc domains into a distinct heterodimeric Fc region. This term also encompasses single-chain Fc regions in which the constituent Fc domains are linked together by a linker moiety.

[0127] As used herein, the term "FcRn binding fragment" refers to a portion of an Fc region sufficient to confer an FcRn bond.

[0128] As used herein, the term “EU position” refers to Edelman, GM et al., Proc. Natl. Acad. USA, 1969; 63, 78-85, and Kabat et al., “Sequences of Proteins of Immunological Interest,” USDept. Health and Human Services, 5 th This refers to the amino acid position in the EU numbering system for the Fc region, as described in edition 1991.

[0129] As used herein, the term “baseline” refers to a measurement, for example, in the patient’s blood, prior to the first dose (e.g., intravenous or subcutaneous administration) of treatment (e.g., an FcRn antagonist).

[0130] As used herein, the terms “to treat,” “to treat,” and “treatment” refer to the therapeutic or preventive measures described herein. A “treatment” method involves administering a polypeptide to a subject who has or is susceptible to a disease or disorder in order to prevent, cure, delay, reduce the severity of, or improve one or more symptoms of a disease or disorder, or a recurrent disease or disorder, or to extend the survival of the subject beyond the survival expected in the absence of such treatment.

[0131] As used herein, in the context of therapy, the term “effective dose” refers to the amount of therapy that achieves the desired preventive or therapeutic effect.

[0132] As used herein, the terms “dose” or “medication” refer to the amount of drug administered to a subject in a single dose.

[0133] As used herein, the terms “fixed dose” or “uniform dose” both refer to a dose that does not change based on the characteristics of the subject (e.g., weight, e.g., within a set range; sex; age, e.g., within a set range, etc.).

[0134] As used herein, the terms “control of disease activity” or “CDA” refer to a point in time when there is no further clinical exacerbation and / or an ECI.

[0135] As used herein, the term “remission” refers to complete remission or partial remission.

[0136] As used herein, the terms “complete remission” or “CR” refer to the absence of symptoms as measured by the standard diagnostic criteria for CIDP.

[0137] As used herein, the terms “partial remission” or “PR” refer to a situation in which a patient experiences an ECI (exceptional clinical intervention) but does not experience a CR (complete remission).

[0138] As used herein, “evidence of clinical improvement” or “ECI” means improvement in symptoms as measured by any of the standard CIDP assessment methods, including but not limited to (i) the INCAT disability scale, (ii) the MRC scale (Vanhoutte et al., 2012), (iii) the I-RODS, (iv) the mean grip strength test, and (v) the TUG test. In preferred embodiments, ECI refers to improvement in symptoms as measured using the INCAT disability scale, specifically a decrease in the INCAT score or a decrease in the aINCAT score. In some embodiments, ECI refers to clinical improvement in a parameter that the patient worsened during the period between screening and Stage A (I-RODS, grip strength), or clinical improvement in INCAT.

[0139] As used herein, the term “relapse” refers to a patient with CIDP who presents evidence of clinical exacerbation after a period of remission (partial or complete remission). In other words, “relapse” refers to evidence of clinical exacerbation in a patient with CIDP after a period of remission (partial or complete remission).

[0140] As used herein, the terms “exacerbation” or “clinical exacerbation” refer to an exacerbation of any of the CIDP symptoms. The absence of an exacerbation of CIDP symptoms may be measured using any one of the following: the INCAT score, the MRC total score, the I-RODS, the mean grip strength test, or the TUG test. As used herein, the terms “evidence of clinical exacerbation,” “evidence of clinically significant exacerbation,” and “ECMD” may be used interchangeably. In some embodiments, ECMD is defined as an increase of one or more points in the aINCAT score and / or a decrease of four or more points in the I-RODS (using the centile metric) and / or a decrease of 8 kPa or more in mean grip strength in one hand using a handheld dynamometer. In some embodiments, ECMD is defined as an increase of one point in the aINCAT score occurring two times within seven days of each other. In some embodiments, ECMD is defined as an increase of two or more points in the aINCAT score in a single instance. In some embodiments, ECMD is defined as a decrease of 10% in the I-RODS.

[0141] As used herein, the terms “subject,” “patient,” or “participant” include any human or non-human animal. In one embodiment, the subject, patient, or participant is a human or non-human mammal. In one embodiment, the subject, patient, or participant is a human.

[0142] As used herein, the terms “about” or “approximately” include a variation of ±5% of a given value or range when referring to a measurable value, for example, a dosage, where appropriate for carrying out the methods disclosed herein.

[0143] As used herein, the term “biosimilar” refers to a biological product that is very similar to a reference product and has no clinically significant differences. As used herein, the term “reference product” refers to a biological product that is approved for clinical use. In some embodiments, the reference product is approved in at least one of the following countries: the United States, Europe, China, or Japan. Biosimilars may have minor differences in clinically inactive components. Biosimilars may include minor modifications to the amino acid sequence, such as N-terminal or C-terminal cleavage, which are not expected to alter the biosimilar performance compared to the reference product.

[0144] Where used herein, “no clinically significant difference” is used to determine safety, purity, and efficacy. For example, a biosimilar is compared to and evaluated against a reference product to verify that the biosimilar does not have a clinically significant difference from the reference product in terms of safety, purity, and efficacy. In some embodiments, the determination that there is no clinically significant difference between the biosimilar and the reference product is based on data derived from: (a) analytical studies demonstrating that the biologic is very similar to the reference product despite minor differences in clinically inactive components; (b) animal studies (including, e.g., toxicity assessments); and / or (c) sufficient clinical studies (including, e.g., immunogenicity and pharmacokinetic or pharmacodynamic assessments) to demonstrate safety, purity, and efficacy under one or more appropriate conditions of use in which the reference product is licensed and for which a license is required for the biosimilar. A biosimilar may be an interchangeable product that can be substituted in place of the reference product at a pharmacy without intervention from a prescribing healthcare professional. To meet the "interchangeability" criterion, the biosimilar is expected to produce the same clinical outcomes as the reference product in any given patient, and if the biosimilar is administered to an individual more than once, the risk in terms of reduced safety or efficacy of alternating or switching between the use of the biosimilar and the reference product is not greater than the risk of using the reference product without such alternation or switching. In some embodiments, the biosimilar utilizes the same mechanism of action as the reference product for the proposed conditions of use, to the extent that the mechanism is known for the reference product. In some embodiments, the proposed conditions of use, whether specified, recommended, or proposed in the labeling for the biosimilar, have been previously approved for the reference product. In some embodiments, the route of administration, dosage form, and / or content of the biosimilar are the same as those of the reference product, and the biosimilar is manufactured, processed, packaged, or stored in a facility that meets standards designed to ensure that the biosimilar is safe, pure, and potent.

[0145] As used herein, the terms “label,” “product label,” or “approved product label” refer to information provided to patients and / or healthcare providers that provides relevant information about the approved product. Such information includes, but is not limited to, a description of the approved product, clinical pharmacology, indications (use of the approved product), contraindications (people who should not take the approved product), warnings, precautions, adverse events (side effects), drug abuse and dependence, dosage and administration, use during pregnancy, use in lactating mothers, use in pediatric and elderly patients, methods of supplying the approved product, patient safety information, or one or more of any combination thereof. In some embodiments, the label identifies efgartigimod and provides instructions for its use in patients.

[0146] As used herein, the term “clinically proven effective” refers to regulatory decisions made based on clinical efficacy and other data. Efficacy may be measured based on changes in the course of the disease in response to the drug of this disclosure. For example, the FcRn antagonist of this disclosure (e.g., fgultigimod) is administered to a subject in an amount and time sufficient to induce improvement, preferably sustained improvement, in at least one indicator reflecting the severity of the disorder being treated. Various indicators reflecting the extent of the subject’s disease, illness, or condition may be evaluated to determine whether the amount and time of treatment are sufficient. Such indicators include, for example, clinically recognized indicators of disease severity, symptoms, or signs of the disorder in question. The degree of improvement is generally determined by a physician capable of making this determination based on signs, symptoms, blood samples, or other test results, and may also be determined by questionnaires administered to the subject, such as quality of life questionnaires developed for a given disease. For example, the FcRn antagonist of this disclosure may be administered to achieve improvement in the condition of a subject associated with CIDP. Improvement may be indicated by an improvement in an indicator of disease activity, an improvement in clinical symptoms, or any other measure of disease activity. Improvement in the subject's condition related to CIDP can be measured using any of the standard CIDP assessment methods described herein, such as the method used to define ECI. In some embodiments, clinical effectiveness is defined as demonstrating ECI in the subject. In some embodiments, clinical effectiveness is demonstrated by the length of time the subject remains relapse-free. In some embodiments, clinical effectiveness is demonstrated by a reduced risk of clinical exacerbation (such as ECMD).

[0147] Where used herein, the term “clinically proven safety” refers to a dose, administration regimen, treatment, or method of using the FcRn antagonist (e.g., fgartigimod) of this disclosure, and means a favorable risk-to-benefit ratio with an acceptable frequency and / or acceptable severity of treatment-induced adverse events (AEs or TEAEs) compared to standard treatment or another comparator. Where used herein, “adverse event,” “treatment-induced adverse event,” and “adverse reaction” mean any adverse, undesirable, unintended, or undesirable sign or outcome associated with or caused by the administration of a pharmaceutical composition or therapeutic agent. It is an inappropriate medical event that occurs in a subject to which the drug has been administered. However, abnormal values ​​or observations are not reported as adverse events unless they are considered clinically significant by the principal investigator. If the adverseness or undesirable outcome of an adverse event reaches such a severity, regulatory authorities may consider the pharmaceutical composition or therapeutic agent unacceptable for the proposed use. Specifically, with respect to the dose, administration regimen, or treatment of an FcRn antagonist as described herein, “safe” means having an acceptable frequency and / or acceptable severity of adverse events associated with the administration of the FcRn antagonist, where attribution is considered possible, likely, or very likely to be caused by the use of the FcRn antagonist.

[0148] Where used herein, unless otherwise specified, the term “clinically proven” (used independently or to modify the terms “safety” and / or “efficacy”) means that the clinical trials have proven that they meet the approval standards of the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) of the European Union, the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, and the National Food and Drug Administration (NMPA) of China. For example, a clinical study could be a randomized, double-blind study of appropriate size used to clinically prove the effect of a drug.

[0149] B.FcRn Antagonist FcRn antagonists useful in the methods and uses provided herein may include any molecule that binds to and inhibits FcRn, the molecule including, but not limited to, any anti-FcRn antibody, any anti-FcRn binding region, or any Fc domain or Fc region. In some embodiments, the FcRn antagonists disclosed herein include two, three, or four FcRn binding regions, such as Fc regions. In some embodiments, the FcRn antagonists disclosed herein include one or more Fc regions in combination with one or more Fab regions.

[0150] Any Fc region can be modified to generate variant Fc regions for use in the manner disclosed herein. Generally, the Fc region or its FcRn binding fragments are derived from human immunoglobulins. However, it is understood that the Fc region may originate from immunoglobulins of any other mammalian species, including, for example, camelid species, rodents (e.g., mice, rats, rabbits, guinea pigs), or non-human primates (e.g., chimpanzees, macaques). Furthermore, the Fc region or any part thereof may originate from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, as well as any immunoglobulin isotype, including IgG1, IgG2, IgG3, and IgG4.

[0151] In one embodiment, the Fc region is an IgG Fc region (e.g., a human IgG region). In another embodiment, the Fc region is an IgG1 Fc region (e.g., a human IgG1 region). In yet another embodiment, the Fc region is a chimeric Fc region comprising parts of several different Fc regions. A preferred example of a chimeric Fc region is described in US2011 / 0243966A1, which is incorporated herein by reference in its entirety. Various Fc region gene sequences (e.g., human stationary region gene sequences) are available in the form of publicly available deposits.

[0152] The Fc region may be further cleaved or internally deleted to produce its smallest FcRn-binding fragment. The ability of the Fc region fragment to bind to FcRn can be determined using any binding assay recognized in the art (e.g., ELISA).

[0153] To improve the manufacturability of the FcRn antagonists disclosed herein, it is preferable that the constituent Fc region does not contain any non-disulfide-bonded cysteine ​​residues. Therefore, in one embodiment, the Fc region does not contain any free cysteine ​​residues.

[0154] Any Fc variant or its FcRn binding fragment that specifically binds to FcRn with increased affinity and reduced pH dependence to the natural (i.e., wild-type) Fc region may be used in the methods disclosed herein. In one embodiment, the variant Fc region includes amino acid changes, substitutions, insertions, and / or deletions that confer desired characteristics.

[0155] In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or its FcRn-binding fragment that binds to FcRn at pH 5.5 with higher affinity compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or its FcRn-binding fragment that binds to FcRn at pH 6.0 and / or pH 7.4 with higher affinity compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or its FcRn-binding fragment that binds to FcRn at both acidic and neutral pH with higher affinity.

[0156] In some embodiments, the variant Fc region is derived from the Fc region of any innate immunoglobulin. In some embodiments, the innate immunoglobulin is human immunoglobulin. In some embodiments, the immunoglobulin is IgA, IgD, IgE, or IgG. In some embodiments, the immunoglobulin is IgG. In some embodiments, the immunoglobulin is human IgA, human IgD, human IgE, or human IgG. In some embodiments, the immunoglobulin is human IgG. In some embodiments, IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region is different from the human IgG1 Fc region. In some embodiments, the human IgG1 Fc region includes the G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype.

[0157] In one embodiment, the variant Fc region, or its FcRn binding fragment, consists of two Fc domains. In one embodiment, the FcRn antagonist is an Fc region containing amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0158] In one embodiment, the variant Fc region includes or consists of a first Fc domain and a second Fc domain that form a homodimer or heterodimer. In one embodiment, the first Fc domain and / or the second Fc domain contain amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the first Fc domain and / or the second Fc domain contain amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0159] In some embodiments, the FcRn antagonists disclosed herein include or consist of at least one Fc domain, the amino acid sequence of the at least one Fc domain including or consisting of the amino acid sequence of SEQ ID NO: 22, provided below in Table 1. [Table 1]

[0160] In some embodiments, the FcRn antagonists disclosed herein include or consist of a dimer of a first Fc domain and a second Fc domain, or a variant Fc region comprising the same, wherein the amino acid sequences of the first and second Fc domains include or consist of the amino acid sequence of SEQ ID NO: 22.

[0161] In some embodiments, the FcRn antagonists disclosed herein include, or consist of, an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains include, or consist of, an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1 to 21 (see Table 2 below). In some embodiments, the dimer is a heterodimer or a homodimer. [Table 2] TIFF2026524664000003.tif249170

[0162] In one embodiment, the first Fc domain and / or the second Fc domain include an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4.

[0163] In some embodiments, an FcRn antagonist comprises a population of FcRn antagonist molecules. In some embodiments, an FcRn antagonist comprising a first Fc domain and a second Fc domain containing an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4 is the major FcRn antagonist molecule in the population of FcRn antagonist molecules. In some embodiments, the major FcRn antagonist molecule constitutes at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the population of FcRn antagonist molecules.

[0164] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region includes the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 1.

[0165] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region includes the amino acid sequence of SEQ ID NO: 2.

[0166] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region includes the amino acid sequence of SEQ ID NO: 3.

[0167] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region includes the amino acid sequence of SEQ ID NO: 4.

[0168] In one embodiment, the FcRn antagonist consists of a variant Fc region, the variant Fc region comprises two Fc domains, and the amino acid sequence of each Fc domain is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

[0169] In certain embodiments, the variant Fc region is a heterodimer, and the constituent Fc domains are distinct from each other. Methods for producing Fc heterodimers are known in the art (see, for example, US8,216,805, which is incorporated herein by reference in its entirety). In one embodiment, the FcRn antagonist consists of a variant Fc region, which consists of two Fc domains forming a heterodimer, and the amino acid sequence of each Fc domain is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, which consists of or includes two Fc domains forming a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3.

[0170] In one embodiment, the FcRn antagonist consists of a variant Fc region, the variant Fc region consists of two Fc domains that form a heterodimer, and the amino acid sequence of each Fc domain is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 4. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 4. In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a heterodimer, the amino acid sequence of the first Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 4, and the amino acid sequence of the second Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

[0171] In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a homodimer, and the amino acid sequence of each Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 1.

[0172] In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a homodimer, and the amino acid sequence of each Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 2.

[0173] In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a homodimer, and the amino acid sequence of each Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 3.

[0174] In one embodiment, the FcRn antagonist consists of or includes a variant Fc region, the variant Fc region consists of or includes two Fc domains that form a homodimer, and the amino acid sequence of each Fc domain consists of or includes the amino acid sequence of SEQ ID NO: 4.

[0175] In some embodiments, the FcRn antagonist includes glycanation in one or both of the Fc domains. In some embodiments, the FcRn antagonist molecule includes glycanation at EU position 297 in one or both of the Fc domains. In some embodiments, the glycanation includes an N-glycan. In some embodiments, the N-glycan includes G0F N-glycan, G1F N-glycan, G2F N-glycan, or G0 N-glycan.

[0176] In some embodiments, the FcRn antagonist comprises or consists of a population of FcRn antagonists, where at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, or at least 57% of the population of Fc domains of the FcRn antagonist comprises galactose. In some embodiments, the population includes or consists of FcRn antagonists, and at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the population of Fc domains of the FcRn antagonists include fucose.

[0177] In some embodiments, the FcRn antagonist lacks an amino acid at EU position 441 of one or both Fc domains. In some embodiments, the FcRn antagonist contains glycine and lysine at EU positions 440 and 441, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441. In some embodiments, the FcRn antagonist contains amidated proline at EU position 439. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441 and contains amidated proline at EU position 439.

[0178] In some embodiments, the FcRn antagonist contains aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks an amino acid at EU position 221 and contains lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks an amino acid at EU positions 221 and 222 and contains threonine, histidine, threonine, and cysteine ​​at EU positions 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221-224 and contains threonine and cysteine ​​at EU positions 225 and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221, 222, 223, 224, 225, and 226.

[0179] In some embodiments, an FcRn antagonist is a group of FcRn antagonist molecules. In some embodiments, the group of FcRn antagonist molecules includes or consists of multiple subgroups of FcRn antagonist molecules. In some embodiments, the group of FcRn antagonist molecules includes or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 subgroups.

[0180] In some embodiments, a first subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, and both amino acid sequences of the first and second Fc domains include or comprise an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3.

[0181] In some embodiments, a second subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains being at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs. 3 and 13, respectively.

[0182] In some embodiments, a third subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains being at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs. 3 and 10, respectively.

[0183] In some embodiments, a fourth subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deaminocinated.

[0184] In some embodiments, a fifth subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminocinated.

[0185] In some embodiments, a sixth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains are, respectively, at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs. 2 and 3.

[0186] In some embodiments, a seventh subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains include or comprise an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized.

[0187] In some embodiments, an eighth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 2.

[0188] In some embodiments, a ninth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains are, respectively, at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs. 3 and 7.

[0189] In some embodiments, a 10th subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains being at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs. 2 and 3, respectively, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the 10th subpopulation is oxidized.

[0190] In some embodiments, an eleventh subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and two amino acid residues independently selected from methionine or tryptophan residues in each FcRn antagonist molecule in the eleventh subpopulation are oxidized.

[0191] In some embodiments, the first subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, and the amino acid sequences of both the first and second Fc domains include or comprise the amino acid sequence of SEQ ID NO: 3.

[0192] In some embodiments, the second subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of the first Fc domain and the second Fc domain, and the amino acid sequences of the first and second Fc domains include or comprise the amino acid sequences of SEQ ID NOs: 3 and 13, respectively.

[0193] In some embodiments, a third subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains comprising or consisting of the amino acid sequences of SEQ ID NOs: 3 and 10, respectively.

[0194] In some embodiments, a fourth subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of both the first and second Fc domains include or comprise the amino acid sequence of SEQ ID NO: 3, and two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deaminomethylated.

[0195] In some embodiments, a fifth subpopulation of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains include or comprise the amino acid sequence of SEQ ID NO: 3, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminomethylated.

[0196] In some embodiments, a sixth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains comprising or consisting of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively.

[0197] In some embodiments, a seventh subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains include or comprise the amino acid sequence of SEQ ID NO: 3, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subgroup is oxidized.

[0198] In some embodiments, the eighth subgroup of the FcRn antagonist molecule comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, and the amino acid sequences of both the first and second Fc domains comprise or consist of the amino acid sequence of SEQ ID NO: 2.

[0199] In some embodiments, the ninth subgroup of the FcRn antagonist molecule comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains comprising or consisting of the amino acid sequences of SEQ ID NOs: 3 and 7, respectively.

[0200] In some embodiments, a 10th subgroup of FcRn antagonist molecules includes or comprises a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of the first and second Fc domains include or comprise the amino acid sequences of SEQ ID NOs. 2 and 3, respectively, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the 10th subgroup is oxidized.

[0201] In some embodiments, an eleventh subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, the amino acid sequences of both the first and second Fc domains comprising or consisting of the amino acid sequence of SEQ ID NO: 3, and two amino acid residues independently selected from methionine or tryptophan residues in each FcRn antagonist molecule in the eleventh subgroup are oxidized.

[0202] In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with one of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with two of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with three of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with four of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with five of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with six of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with seven of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with eight of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups. In some embodiments, the group of FcRn antagonist molecules includes or consists of a first subgroup combined with nine of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups.In some embodiments, the population of FcRn antagonist molecules includes or consists of a first subgroup combined with all of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subgroups.

[0203] In some embodiments, the group includes or consists of first and second subgroups. In some embodiments, the group includes or consists of first and third subgroups. In some embodiments, the group includes or consists of first and fourth subgroups. In some embodiments, the group includes or consists of first and fifth subgroups. In some embodiments, the group includes or consists of first and sixth subgroups. In some embodiments, the group includes or consists of first and seventh subgroups. In some embodiments, the group includes or consists of first and eighth subgroups. In some embodiments, the group includes or consists of first and ninth subgroups. In some embodiments, the group includes or consists of first and tenth subgroups. In some embodiments, the group includes or consists of first and eleventh subgroups. In some embodiments, the groups listed above further include or consist of 1, 2, 3, 4, 5, 6, 7, 8, or 9 additional subgroups. In some embodiments, these additional subgroups are one or more of the above.

[0204] In some embodiments, the group includes or consists of the first, seventh, ninth, or eleventh subgroups.

[0205] In some embodiments, the first subgroup constitutes at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup constitutes about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, or about 90% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup constitutes 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup constitutes 40%–90%, 50%–80%, or 55%–70% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup constitutes 56.9%–68.3% or 59.5%–67.9% of the population of FcRn antagonist molecules.

[0206] In some embodiments, the second subgroup constitutes less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subgroup constitutes about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subgroup constitutes 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subgroup constitutes 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation constitutes 0.8%–2.0% or 0.8%–2.1% of the population of FcRn antagonist molecules.

[0207] In some embodiments, the third subgroup constitutes less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subgroup constitutes about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subgroup constitutes 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subgroup constitutes 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes 1.1%–2.1% or 1.0%–1.9% of the population of FcRn antagonist molecules.

[0208] In some embodiments, the fourth subgroup constitutes less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subgroup constitutes about 5%, about 4%, about 3%, about 2%, or about 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subgroup constitutes 5%, 4%, 3%, 2%, or 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subgroup constitutes 1% to 5%, 2% to 4%, or 2% to 3% of the population of FcRn antagonist molecules. In some embodiments, the fourth subgroup constitutes 2.1% to 3.2% or 2.0% to 3.1% of the population of FcRn antagonist molecules.

[0209] In some embodiments, the fifth subgroup constitutes less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, or less than 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subgroup constitutes about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, about 6%, or about 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subgroup constitutes 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subgroup constitutes 5% to 12%, 6% to 10%, or 7% to 8% of the population of FcRn antagonist molecules. In some embodiments, the fifth subgroup constitutes 6.8%–9.4% or 6.9%–8.7% of the population of FcRn antagonist molecules.

[0210] In some embodiments, the sixth subgroup constitutes less than 17%, less than 16%, less than 15%, less than 14%, less than 13%, less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, or less than 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subgroup constitutes about 17%, about 16%, about 15%, about 14%, about 13%, about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, or about 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subgroup constitutes 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, or 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subgroup constitutes 7%–17%, 10%–15%, or 11%–12% of the population of FcRn antagonist molecules. In some embodiments, the sixth subgroup constitutes 7.0%–14.0% or 10.0%–14.4% of the population of FcRn antagonist molecules.

[0211] In some embodiments, the seventh subpopulation constitutes less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation constitutes about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subgroup constitutes 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecule population. In some embodiments, the seventh subgroup constitutes 0.5%–5.5%, 1.0%–3.0%, or 1.5%–2.5% of the FcRn antagonist molecule population. In some embodiments, the seventh subgroup constitutes 1.5%–5.5% or 1.4%–4.9% of the FcRn antagonist molecule population.

[0212] In some embodiments, the eighth subpopulation constitutes less than 7.5%, less than 7.0%, less than 6.5%, less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, or less than 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation constitutes about 7.5%, about 7.0%, about 6.5%, about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, or about 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subgroup constitutes 7.5%, 7.0%, 6.5%, 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, or 2.5% of the FcRn antagonist molecule population. In some embodiments, the eighth subgroup constitutes 2.5%–7.5%, 3.0%–5.0%, or 3.5%–4.5% of the FcRn antagonist molecule population. In some embodiments, the eighth subgroup constitutes 2.9%–7.4% or 3.0%–6.3% of the FcRn antagonist molecule population.

[0213] In some embodiments, the ninth subgroup constitutes less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subgroup constitutes about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subgroup constitutes 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subgroup constitutes 0.5% to 3.5%, 1.5% to 2.0%, or 1.0% to 1.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes 0.4%–3.2% or 0.5%–2.6% of the population of FcRn antagonist molecules.

[0214] In some embodiments, the 10th subgroup constitutes less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 10th subgroup constitutes about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 10th subgroup constitutes 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 10th subgroup constitutes 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules.

[0215] In some embodiments, the 11th subgroup constitutes less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subgroup constitutes about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subgroup constitutes 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subgroup constitutes 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules.

[0216] In some embodiments, the group of FcRn antagonist molecules includes one or more of the FcRn antagonists described herein. In some embodiments, the FcRn antagonist is one of those described in U.S. Patent Application No. 63 / 383,599, filed November 14, 2022, which is incorporated herein by reference in its entirety. In some embodiments, the FcRn antagonist is a group of FcRn antagonists described in U.S. Patent Application No. 63 / 383,599, filed November 14, 2022, which is incorporated herein by reference in its entirety.

[0217] In one embodiment, the FcRn antagonist is evgarchigimod (CAS Registry No. 1821402-21-4). Evgarchigimod is described in more detail below herein. As used herein, the term "evgarchigimod" is interchangeable with "evgarchigimod alpha". In some embodiments, evgarchigimod is evgarchigimod alpha-fcab.

[0218] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), olilanorimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161).

[0219] In one embodiment, an antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is nipocalimab, also known as M281. Nipocalimab is a full-length "Fc-dead" IgG1 monoclonal antibody. Nipocalimab has been administered as an intravenous infusion in a phase 2 clinical trial for the treatment of myasthenia gravis (MG), warm autoimmune hemolytic anemia (WAIHA), and hemolytic disease of the fetus and neonatal disease (HDFN). Nipocalimab contains the light chain (SEQ ID NO: 23) and heavy chain (SEQ ID NO: 24) sequences shown in Table 3 below. [Table 3]

[0220] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is rozanolixizumab, also known as UCB7665. Rozanolixizumab is a full-length humanized IgG4 monoclonal antibody. Rozanolixizumab is administered as a subcutaneous injection in ongoing clinical trials for MG, immunothrombocytopenia (ITP), and CIDP. Rozanolixizumab contains the light chain (SEQ ID NO: 25) and heavy chain (SEQ ID NO: 26) sequences shown in Table 4 below. [Table 4]

[0221] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is olilanorimab, also known as SYNT001. Olilanorimab is another full-length humanized IgG4 monoclonal antibody. Olilanorimab has been administered as an intravenous infusion in a phase 2 clinical trial for the treatment of WAIHA. Olilanorimab contains the light chain (SEQ ID NO: 27) and heavy chain (SEQ ID NO: 28) sequences shown in Table 5 below. [Table 5]

[0222] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is batoclimab, also known as IMVT1401 / RVT1401 / HBM9161. Batoclimab is another full-length "Fc-dead" IgG1 monoclonal antibody. Batoclimab is administered as subcutaneous injection in an ongoing phase 2 clinical trial for the treatment of MG and Graves' ophthalmopathy. Batoclimab contains the light chain (SEQ ID NO: 29) and heavy chain (SEQ ID NO: 30) sequences shown in Table 6 below. [Table 6]

[0223] In some embodiments, the anti-FcRn antibody for use by the method and use described herein is one of the anti-FcRn antibodies described in International Patent Application No. 2015 / 167293A1, the contents of which are incorporated herein in their entirety. In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulin to FcRn is IMVT-1402 (Immunovant).

[0224] C. Pharmaceutical Compositions This disclosure provides pharmaceutical compositions comprising FcRn antagonists for use in methods of treating CIDP. In certain embodiments, these compositions comprise or consist of a variant Fc region or its FcRn-binding fragment that specifically binds to FcRn, particularly human FcRn, with increased affinity and reduced pH dependence to the native Fc region. In other embodiments, the FcRn antagonist composition is an antibody or its antigen-binding fragment that specifically binds to FcRn via its antigen-binding domain and inhibits the binding of immunoglobulin Fc regions to FcRn. Generally, these FcRn antagonists inhibit the binding of Fc-containing drugs (e.g., antibodies and immunoadhesins) to FcRn in vivo, resulting in an increased degradation rate of Fc-containing drugs and, at the same time, reduced serum levels of these drugs.

[0225] In one embodiment, the FcRn antagonist is efgultigimod or a biosimilar version thereof. Efgultigimod (ARGX-113) is a modified human immunoglobulin (Ig) gamma (IgG) 1-derived Fc allotype that binds to human FcRn with nanomolar affinity. Efgultigimod contains the IgG1 Fc region (encompassing the residue of SEQ ID NO: 2) and is manipulated using ABDEG® technology to increase its affinity for FcRn at both physiological and acidic pH. See Vaccaro C et al., Nat Biotechnol. 2005;23(10):1283. See also U.S. Patent No. 10,316,073, the contents of which are incorporated herein by reference in their entirety. The increased affinity of efgultigimod for FcRn at both acidic and physiological pH results in the blockage of FcRn-mediated recirculation of IgG.

[0226] Efgultigimod has a molecular weight of approximately 54 kDa, which is about one-third the molecular weight of full-length IgG (MW approximately 150 kDa). Therefore, 10 mg of efgultigimod is approximately 185 nmol, and 25 mg of efgultigimod is approximately 462.5 nmol. In contrast, 10 mg of full-length IgG antibody is approximately 67 nmol / kg body weight. Furthermore, a fixed dose of 1000 mg of efgartigimod is equivalent to a fixed dose of approximately 18,500 nmol of efgartigimod, while a fixed dose of 2000 mg of efgartigimod is equivalent to a fixed dose of approximately 37,000 nmol of efgartigimod.

[0227] Due to its increased affinity for FcRn at both acidic and neutral pH levels, efgultigimod blocks the formation of FcRn / IgG complexes, resulting in the degradation of endogenous IgG, including autoantibodies that cause IgG-mediated autoimmune diseases. This blockade of FcRn by efgultigimod leads to a rapid and marked reduction in autoantibody levels, which forms the basis for therapeutic strategies for treating autoimmune indications in which IgG autoantibodies are expected to play a central role in the disease pathogenesis.

[0228] Efgultigimod, registered as VYVGART®, is a prescription drug approved in the United States, Europe, the United Kingdom, China, Canada, and Israel for the treatment of adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) antibodies, and in Japan for the treatment of adults with gMG who do not respond well to steroids or nonsteroidal immunosuppressive therapy (IST). Efgultigimod is also approved in Japan for the treatment of chronic ITP. Efgultigimod is under development for both intravenous (IV) and subcutaneous (SC) administration routes for multiple indications.

[0229] In certain embodiments of SC administration, efgultigimod may be administered alone. Alternatively, in certain embodiments of SC administration, efgultigimod may be co-formulated with hyaluronidase, for example, rHuPH20 (recombinant human PH20), and administered. The co-formulated material allows for higher volume dosing.

[0230] rHuPH20 is the active ingredient in the commercially available halozyme product HYLENEX® Recombinant (Hyaluronidase Hit Injection), which was marketed in the United States in December 2005 and approved for use by the FDA. HYLENEX® is a tissue permeability modifier indicated as an adjuvant in SC urography to achieve hydration, to increase the dispersion and absorption of other injected drugs, and to improve the reabsorption of radiopaque agents.

[0231] rHuPH20 is a recombinant human hyaluronidase produced by genetically engineered Chinese hamster ovary (CHO) cells, and contains a deoxyribonucleic acid plasmid encoding a soluble fragment of human hyaluronidase (occipital protein 20 [PH20]).

[0232] HZ202 rHuPH20 DS is currently registered under HYLENEX® and other biopharmaceutical products co-formulated with rHuPH20 DS. Therefore, in certain embodiments, HZ202 rHuPH20 DS is used in products co-formulated with efgultigimod / rHuPH20 for SC administration (i.e., efgultigimod PH20SC).

[0233] Efgultigimod PH20SC is currently registered as VYVGART® HYTRULO, approved by the U.S. FDA in 2023 for the treatment of gMG in adult patients who are AChR antibody positive. VYVGART® HYTRULO contains 1,008 mg of efgultigimod alpha and 11,200 units of hyaluronidase (180 mg / 2,000 units per mL) in a single-dose vial. In certain embodiments, efgultigimod PH20SC (also referred to as efgultigimod PH20) is used in the methods described herein.

[0234] Soluble hyaluronidases are provided herein in co-formulations, combinations, uses, and methods. Soluble hyaluronidases include any that are secreted from cells and exist in a soluble form upon expression. Such soluble hyaluronidases include, but are not limited to, bacterial soluble hyaluronidases, non-human soluble hyaluronidases, e.g., bovine PH20 and sheep PH20, human soluble PH20, and their variants. Generally, soluble forms of PH20 are produced using a protein expression system, which facilitates accurate N-glycosylation to ensure that the polypeptide retains its activity, because glycosylation is important for the catalytic activity and stability of hyaluronidases. Such cells include, for example, Chinese hamster ovary (CHO) cells (e.g., DG44 CHO cells).

[0235] In some embodiments, rHuPH20 refers to a composition produced upon expression in cells, for example, CHO cells, and generally consists of nucleic acids encoding residues 36-482 of SEQ ID NO: 32, linked to a native or heterologous signal sequence (residues 1-35 of SEQ ID NO: 32). rHuPH20 is produced by the expression of nucleic acid molecules, for example, nucleic acid molecules encoding amino acids 1-482 (as described in SEQ ID NO: 32), in mammalian cells. Translational processing removes the 35-amino acid signal sequence. When produced in culture medium, there is heterogeneity at the C-terminus, and thus the product referred to as rHuPH20 contains a mixture of species that may include one or more polypeptides 36-480, 36-481, and 36-482 of SEQ ID NO: 32, as well as several shorter polypeptides, in varying abundances. Typically, rHuPH20 is produced in cells that facilitate precise N-glycosylation and retain activity, such as CHO cells (e.g., DG44 CHO cells). In some embodiments, one of the most abundant species is a 446-amino acid polypeptide corresponding to residues 36-481 of SEQ ID NO: 32. In some embodiments, rHuPH20 refers to a polypeptide that is soluble or secreted upon expression in mammalian cells and has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity with residues 36-482 of SEQ ID NO: 32. In some embodiments, rHuPH20 is the 447-amino acid polypeptide of SEQ ID NO: 33. [Table 7]

[0236] SC injection volume is typically limited to 2.5 mL due to concerns about injection pain associated with larger volumes. rHuPH20 has been shown to offer a solution to the volume limitations associated with rapid SC injection. rHuPH20 acts locally and transiently to depolymerize hyaluronan, a gel-like substance found in the subcutaneous layer of the skin. This results in reduced resistance to fluid flow, potentially increasing the dispersion and absorption of the injected drug and fluid, allowing larger volumes to be injected with limited swelling or pain. rHuPH20 has been shown to enable rapid absorption of relatively large volumes (10 mL) when SC is administered (Shpilberg O et al., 2013). When SC was administered using rHuPH20 at 2000 U / mL in 10 mL of IgG solution, little to no injection site swelling was observed, whereas significant injection site swelling was observed when 10 mL of IgG solution was injected without rHuPH20 (Shpilberg O et al., 2013).

[0237] rHuPH20 acts transiently and is not systematically absorbed. This has been shown to prevent long-term topical effects. rHuPH20 has a half-life of less than 30 minutes in the skin. Hyaluronan levels in subcutaneous tissue return to normal within 24-48 hours due to the rapid natural metabolic turnover of hyaluronan.

[0238] rHuPH20 is approved in the United States and Europe for SC administration in co-formulations with other active ingredients (RITUXAN HYCELA® / MABTHERA® SC [rituximab] for non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and HERCEPTIN HYLECTA® / HERCEPTIN® SC [trastuzumab]) with an enzyme concentration of 2000 U / mL and an injectable volume ranging from 5 to 13.4 mL.

[0239] In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 300 mg to about 6,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 750 mg to about 3,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 1,000 mg to about 2,500 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from about 1,000 mg to about 2,000 mg.

[0240] In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 20 mg to 20,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 200 mg to 20,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 300 mg to 6,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 750 mg to 3,000 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 1,000 mg to 2,500 mg. In some embodiments, the pharmaceutical formulation contains an amount of FcRn antagonist ranging from 1,000 mg to 2,000 mg.

[0241] In some embodiments, the pharmaceutical formulation comprises about 1000 mg or about 2000 mg of an FcRn antagonist. In some embodiments, the pharmaceutical formulation comprises 1000 mg or 2000 mg of an FcRn antagonist. In some embodiments, the FcRn antagonist is efgaltigimod.

[0242] In some embodiments, the pharmaceutical formulation contains efgartigimod in an amount of about 800 mg to about 1200 mg. In some embodiments, the pharmaceutical formulation contains about 1000 mg of efgartigimod. In some embodiments, the pharmaceutical formulation contains 1000 mg of efgartigimod.

[0243] In some embodiments, the pharmaceutical formulation contains efgartigimod in an amount of about 10 mg / mL to about 200 mg / mL.

[0244] In some embodiments, the pharmaceutical formulation contains approximately 20 mg / mL of efgartigimod.

[0245] In some embodiments, the pharmaceutical formulation contains approximately 180 mg / mL of efgartigimod.

[0246] In some embodiments, the pharmaceutical formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

[0247] Hyaluronidase can be present in the pharmaceutical formulation in any preferred amount. In one embodiment, the amount of hyaluronidase is about 1000 U / mL to about 3000 U / mL. In one embodiment, the amount of hyaluronidase is about 1000 U / mL, about 1500 U / mL, about 2000 U / mL, about 2500 U / mL, or about 3000 U / mL. In one embodiment, the amount of hyaluronidase is 2000 U / mL.

[0248] In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of about 11,000 U or about 22,000 U. In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of 11,000 U or about 22,000 U. In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of about 11,200 U. In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of 11,200 U.

[0249] In some embodiments, the pharmaceutical formulation contains at least about 5 U to at least about 100,000 U of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation contains at least about 5 U, at least about 10 U, at least about 20 U, at least about 30 U, at least about 40 U, ​​at least about 50 U, at least about 75 U, at least about 100 U, at least about 200 U, at least about 300 U, at least about 400 U, at least about 500 U, at least about 750 U, at least about 1000 U, at least about 2000 U, at least about 3000 U, at least about 4000 U, at least about 5000 U, and less It contains at least approximately 6,000 U, at least approximately 7,000 U, at least approximately 8,000 U, at least approximately 9,000 U, at least approximately 10,000 U, at least approximately 20,000 U, at least approximately 30,000 U, at least approximately 40,000 U, at least approximately 50,000 U, at least approximately 60,000 U, at least approximately 70,000 U, at least approximately 80,000 U, at least approximately 90,000 U, or at least approximately 100,000 U of endoglycosidase hydrolase enzyme.

[0250] In some embodiments, the pharmaceutical formulation contains about 20,000 U of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation contains at least about 500 U / mL to at least about 5000 U / mL of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation contains at least about 1500 U / mL, at least about 1600 U / mL, at least about 1700 U / mL, at least about 1800 U / mL, at least about 1900 U / mL, at least about 2000 U / mL, at least about 2100 U / mL, at least about 2200 U / mL, at least about 2300 U / mL, at least about 2400 μM, at least about 2500 μM, at least about 3000 μM, at least about 3500 μM, at least about 4000 μM, at least about 4500 U / mL, or at least about 5000 U / mL of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation contains approximately 2000 U / mL of endoglycosidase hydrolase enzyme.

[0251] In some embodiments, the endoglycosidase hydrolase enzyme cleaves hyaluronic acid in hexosaminide β(1-4) or (1-3) linkages. In some embodiments, the endoglycosidase hydrolase enzyme comprises the catalytic domain of hyaluronidase PH-20 (HuPH20), HYAL1, HYAL2, HYAL3, HYAL4, or HYALPS1. In some embodiments, the endoglycosidase hydrolase enzyme comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% sequence identity with amino acids 36-490 of SEQ ID NO: 32. In some embodiments, the endoglycosidase hydrolase enzyme comprises hyaluronidase. In some embodiments, the endoglycosidase hydrolase enzyme comprises a hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, any variant thereof, and any isoform thereof. In some embodiments, the endoglycosidase hydrolase enzyme comprises rHuPH20 or a fragment thereof.

[0252] In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified hyaluronidase comprising one or more amino acid substitutions in the alpha-helix region of a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or fragments thereof. In some embodiments, the endoglycosidase hydrolase enzyme includes a modified hyaluronidase in which one or more N-terminal and / or C-terminal amino acids are deleted from a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or fragments thereof. In some embodiments, the endoglycosidase hydrolase enzyme includes a modified rHuPH20, which includes i. one or more amino acid substitutions in the alpha-helix region, linker region, or both the alpha-helix region and linker region compared to wild-type rHuPH20; ii. one or more N-terminal amino acids, one or more C-terminal amino acids, or one or more N-terminal amino acids and one or more C-terminal amino acids compared to wild-type rHuPH20; or iii. both of (i) and (ii).

[0253] As used herein, “hyaluronidase” refers to an enzyme capable of catalyzing the cleavage of hyaluronan. Hyaluronan is a repeat polymer of N-acetylglucosamine and glucuronic acid, which resides in the subcutaneous space and contributes to the soluble gel-like components of the extracellular matrix of the skin, which are restored by rapid turnover (resynthesis). In some embodiments, hyaluronidase comprises rHuPH20, a glycosylated 447-amino acid single-chain polypeptide that locally depolymerizes hyaluronan in the subcutaneous space at the injection site in the skin. Depolymerization of hyaluronan by hyaluronidase is achieved by hydrolysis of the polysaccharide polymer. Depolymerization of hyaluronan results in a transient reduction in the viscosity of the gel-like phase of the extracellular matrix and increased water-permeable conductance, which facilitates the dispersion and absorption of co-administered therapeutic agents. Therefore, hyaluronidases, such as rHuPH20, can improve the rate and ease of subcutaneous delivery of injectable biologics and drugs by acting as permeation enhancers. In certain embodiments, the hyaluronidase includes ENHANZE®.

[0254] In some embodiments, the pharmaceutical formulation contains, at a pH of about 6.0, about 180 mg / mL of an FcRn antagonist, about 2,000 U / mL of rHuPH20, about 1.4 mg / mL of L-histidine, about 2.2 mg / mL of L-histidine hydrochloride monohydrate, about 1.5 mg / mL of L-methionine, about 0.4 mg / mL of polysorbate 20, about 5.8 mg / mL of sodium chloride, and about 20.5 mg / mL of sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0255] In some embodiments, the pharmaceutical formulation comprises, at a pH of approximately 6.0, 180 mg / mL of FcRn antagonist, 2,000 U / mL of rHuPH20, 1.4 mg / mL of L-histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of L-methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, and 20.5 mg / mL of sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0256] In some embodiments, the pharmaceutical formulation contains, at a pH of about 6.0, about 180 mg / mL of efgaltigimod, about 2,000 U / mL of rHuPH20, about 1.4 mg / mL of L-histidine, about 2.2 mg / mL of L-histidine hydrochloride monohydrate, about 1.5 mg / mL of L-methionine, about 0.4 mg / mL of polysorbate 20, about 5.8 mg / mL of sodium chloride, and about 20.5 mg / mL of sucrose.

[0257] In some embodiments, the pharmaceutical formulation contains, at a pH of approximately 6.0, 180 mg / mL of efgaltigimod, 2,000 U / mL of rHuPH20, 1.4 mg / mL of L-histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of L-methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, and 20.5 mg / mL of sucrose.

[0258] In some embodiments, the pharmaceutical formulation comprises, at a pH of about 6.0, about 180 mg / mL of FcRn antagonist, about 2,000 U / mL of rHuPH20, about 20 mM L-histidine / L-histidine HCl, about 10 mM L-methionine, about 0.04% (w / v) of polysorbate 20, about 100 mM sodium chloride, and about 60 mM sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0259] In some embodiments, the pharmaceutical formulation comprises, at a pH of approximately 6.0, 180 mg / mL of FcRn antagonist, 2,000 U / mL of rHuPH20, 20 mM L-histidine / L-histidine HCl, 10 mM L-methionine, 0.04% (w / v) of polysorbate 20, 100 mM sodium chloride, and 60 mM sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0260] In some embodiments, the pharmaceutical formulation contains, at a pH of about 6.0, about 180 mg / mL of efgaltigimod, about 2,000 U / mL of rHuPH20, about 20 mM of L-histidine / L-histidine HCl, about 10 mM of L-methionine, about 0.04% (w / v) of polysorbate 20, about 100 mM of sodium chloride, and about 60 mM of sucrose.

[0261] In some embodiments, the pharmaceutical formulation comprises 180 mg / mL of efgaltigimod, 2,000 U / mL of rHuPH20, 20 mM L-histidine / L-histidine HCl, 10 mM L-methionine, 0.04% (w / v) of polysorbate 20, 100 mM sodium chloride, and 60 mM sucrose, at a pH of approximately 6.0.

[0262] In any of the embodiments described above, the pharmaceutical preparation may be in unit dosage form.

[0263] In one embodiment, the unit dosage form comprises an FcRn antagonist as a dry formulation for dissolution, such as a lyophilized powder, freeze-dried powder, or anhydrous concentrate. In one embodiment, the dry formulation is contained in a sealed container such as a vial, ampoule, or sachet.

[0264] In one embodiment, the unit dosage form comprises a liquid formulation, for example, an FcRn antagonist as an injection or infusion solution. In one embodiment, the liquid formulation is contained in a sealed container such as a vial, sachet, pre-filled syringe, pre-filled auto-injector, or cartridge for a reusable syringe or applicator. In one embodiment, the liquid formulation is contained in a single-dose vial.

[0265] In one embodiment, the unit dose per vial may contain an FcRn antagonist in the range of approximately 500 to approximately 2500 mg or approximately 1000 mg to approximately 2000 mg, in volumes of 0.5 mL, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 15 mL, or 20 mL. In some embodiments, the unit dose per vial contains 1008 mg of FcRn antagonist in 5.6 mL. In some embodiments, the unit dose per vial contains 1008 mg of FcRn antagonist and 11,200 U of hyaluronidase in 5.6 mL. In one embodiment, these preparations can be adjusted to the desired concentration by adding a sterile diluent to each vial.

[0266] In some embodiments, the unit dosage form is a single-dose vial containing at least 5.6 mL of a liquid formulation comprising an FcRn antagonist at a concentration of 180 mg / mL. In some embodiments, the single-dose vial contains 5.6 mL of a liquid formulation comprising 1,008 mg of an FcRn antagonist and 11,200 units of hyaluronidase (recombinant human). Each mL of the vial solution has a pH of 6.0 and contains 180 mg of fgartigimod alfa, 2,000 units of hyaluronidase (recombinant human), and histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP. In some embodiments, the FcRn antagonist is efgultigimod or a biosimilar version thereof.

[0267] The formulations disclosed herein include bulk pharmaceutical compositions useful in the manufacture of pharmaceutical compositions (e.g., compositions suitable for administration to a subject or patient) that can be used to prepare unit dosage forms. In one embodiment, the composition of the invention is a pharmaceutical composition. Such compositions include a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents (e.g., an FcRn antagonist of the invention or other prophylactic or therapeutic agent), and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition is formulated to be suitable for intravenous administration to a subject. In one embodiment, the pharmaceutical composition is formulated to be suitable for subcutaneous administration to a subject. In some embodiments, the pharmaceutical composition is formulated to be suitable for subcutaneous administration to a subject as a once-weekly injection over about 30 - 90 seconds. In some embodiments, the pharmaceutical composition is formulated for subcutaneous use with a winged infusion set.

[0268] In some embodiments, the pharmaceutical compositions described herein are contraindicated in patients with a severe allergy to any of an FcRn antagonist (e.g., efgartigimod), hyaluronidase, or an excipient in the composition. In some embodiments, the allergy is anaphylaxis and / or hypotension causing loss of consciousness.

[0269] D. Kit The present disclosure provides kits comprising an FcRn antagonist and a label. In some embodiments, the kit comprises a pharmaceutical composition comprising an FcRn antagonist and a label. Any FcRn antagonist described herein, or a pharmaceutical composition thereof, can be included in the kits provided herein. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0270] In some embodiments, the pharmaceutical composition comprises, at a pH of about 6.0, about 180 mg / mL of an FcRn antagonist, about 2,000 U / mL of rHuPH20, about 1.4 mg / mL of L-histidine, about 2.2 mg / mL of L-histidine hydrochloride monohydrate, about 1.5 mg / mL of L-methionine, about 0.4 mg / mL of polysorbate 20, about 5.8 mg / mL of sodium chloride, and about 20.5 mg / mL of sucrose. In some embodiments, the FcRn antagonist is efgartigimod or a biosimilar version thereof.

[0271] In some embodiments, the pharmaceutical composition comprises, at a pH of about 6.0, 180 mg / mL of an FcRn antagonist, 2,000 U / mL of rHuPH20, 1.4 mg / mL of L-histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of L-methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, and 20.5 mg / mL of sucrose. In some embodiments, the FcRn antagonist is efgartigimod or a biosimilar version thereof.

[0272] In some embodiments, the pharmaceutical composition comprises, at a pH of about 6.0, about 180 mg / mL of efgartigimod, about 2,000 U / mL of rHuPH20, about 1.4 mg / mL of L-histidine, about 2.2 mg / mL of L-histidine hydrochloride monohydrate, about 1.5 mg / mL of L-methionine, about 0.4 mg / mL of polysorbate 20, about 5.8 mg / mL of sodium chloride, and about 20.5 mg / mL of sucrose.

[0273] In some embodiments, the pharmaceutical composition comprises, at a pH of about 6.0, 180 mg / mL of efgartigimod, 2,000 U / mL of rHuPH20, 1.4 mg / mL of L-histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of L-methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, and 20.5 mg / mL of sucrose.

[0274] In some embodiments, the pharmaceutical composition contains, at a pH of about 6.0, about 180 mg / mL of FcRn antagonist, about 2,000 U / mL of rHuPH20, about 20 mM L-histidine / L-histidine HCl, about 10 mM L-methionine, about 0.04% (w / v) of polysorbate 20, about 100 mM sodium chloride, and about 60 mM sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0275] In some embodiments, the pharmaceutical composition contains, at a pH of about 6.0, 180 mg / mL of FcRn antagonist, 2,000 U / mL of rHuPH20, 20 mM L-histidine / L-histidine HCl, 10 mM L-methionine, 0.04% (w / v) of polysorbate 20, 100 mM sodium chloride, and 60 mM sucrose. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0276] In some embodiments, the pharmaceutical composition, at a pH of about 6.0, comprises about 180 mg / mL of efgaltigimod, about 2,000 U / mL of rHuPH20, about 20 mM of L-histidine / L-histidineHCl, about 10 mM of L-methionine, about 0.04% (w / v) of polysorbate 20, about 100 mM of sodium chloride, and about 60 mM of sucrose.

[0277] In some embodiments, the pharmaceutical composition contains, at a pH of about 6.0, 180 mg / mL of efgaltigimod, 2,000 U / mL of rHuPH20, 20 mM L-histidine / L-histidine HCl, 10 mM L-methionine, 0.04% (w / v) of polysorbate 20, 100 mM sodium chloride, and 60 mM sucrose.

[0278] In some embodiments, the kit includes a single-dose vial containing an FcRn antagonist as a liquid formulation, and a label.

[0279] In some embodiments, a single-dose vial contains 5.6 mL of liquid formulation at pH 6.0, comprising 1,008 mg of FcRn antagonist, 11,200 units of rHuPH20, 7.8 mg of histidine, 12.3 mg of L-histidine hydrochloride monohydrate, 8.4 mg of methionine, 2.2 mg of polysorbate 20, 32.5 mg of sodium chloride, 114.8 mg of sucrose, and water for injection, USP. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0280] In some embodiments, a single-dose vial contains 5.6 mL of a liquid formulation comprising 1,008 mg of FcRn antagonist and 11,200 units of rHuPH20, with each mL of the vial solution having a pH of 6.0 and containing histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP. In some embodiments, the FcRn antagonist is efgaltigimod or a biosimilar version thereof.

[0281] In some embodiments, the label identifies efgultigimod and provides instructions for its use in patients. In some embodiments, the label includes indications for the treatment of CIDP in adult patients. In some embodiments, the label includes data showing an ECI response in 66.5% of a population of CIDP patients who received 1008 mg / 11,200 units of efgultigimod PH20 once weekly. In some embodiments, the label includes data showing improvement over two consecutive visits in 69% of a population of CIDP patients who received 1008 mg / 11,200 units of efgultigimod PH20 once weekly for up to 12 weeks. In some embodiments, improvement is an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in mean grip strength. In some embodiments, the label includes data showing that the median time to the first confirmed ECI in a population of CIDP patients is 43 days from the first dose of efgultigimod PH20. In some embodiments, the labeling indicates that up to 40% of patients had an ECI at week 4, which is the earliest point in time when the ECI criterion can be met. In some embodiments, the labeling indicates that 25% of patients showed a clinically relevant improvement at 9 days in at least one of three parameters (aINCAT, I-RODS, or grip strength). In some embodiments, the labeling includes data indicating that CIDP patients who received the medication experienced a longer time to clinical exacerbation compared to CIDP patients who received placebo, with clinical exacerbation being an increase of 1 or more points in the aINCAT score. In some embodiments, clinical exacerbation is an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation is an increase of 2 or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant.In some embodiments, the label indicates that patients who received efgaltigimod PH20 experienced a longer time to clinical exacerbation (i.e., an increase of 1 or more points in the aINCAT score) compared to patients who received placebo, as demonstrated by a statistically significant hazard ratio of 0.394 [95% CI (0.253; 0.614) p < 0.0001].

[0282] In some embodiments, the labeling includes data showing that CIDP patients in a population of CIDP patients who received efgaltigimod PH20 remained significantly longer relapse-free than CIDP patients in a population of CIDP patients who received placebo. In some embodiments, the labeling includes data showing CIDP patients in a population of CIDP patients who received efgaltigimod PH20 showing a 61% reduction in the risk of exacerbation compared to CIDP patients in a population of CIDP patients who received placebo.

[0283] In some embodiments, the labeling includes data showing a 2% prevalence of anti-efgartigimod alpha antibody in a population of 117 CIDP patients after treatment with a drug. In some embodiments, the labeling includes data showing a 6% prevalence of anti-efgartigimod alpha antibody in a population of 317 CIDP patients after treatment with a drug. In some embodiments, the labeling includes data showing a 0.3% prevalence of neutralizing anti-efgartigimod alpha antibody in a population of 317 CIDP patients after treatment with a drug.

[0284] In some embodiments, the labeling includes a contraindication in patients with severe hypersensitivity to the fgartigimod alfa product, hyaluronidase, or any excipients in their formulations. In some embodiments, the labeling includes a warning for hypersensitivity reactions selected from anaphylaxis and hypotension causing syncope. In some embodiments, the labeling indicates discontinuation of infusion if anaphylaxis or hypotension causing syncope occurs during or within one hour of administration of the product. In some embodiments, the labeling includes a warning for infusion-related reactions selected from hypertension, chills, shivering, chest pain, abdominal pain, and back pain. In some embodiments, the labeling indicates initiating appropriate treatment if a severe infusion-related reaction occurs during administration of the product. In some embodiments, the labeling indicates that if a mild to moderate infusion-related reaction occurs during administration of the product, the patient may be re-challenged with close clinical observation, a slower infusion rate, and pre-medication. In some embodiments, the labeling includes any combination of the features described above or elsewhere in this specification.

[0285] E. Treatment method Subjects to be treated The present invention provides a method for treating CIDP. As described elsewhere in this specification, CIDP is a heterogeneous disorder encompassing disorders with CIDP, primarily characterized by sensory symptoms, distal symmetrical disorders or distal acquired demyelinating symmetrical neuritis (DADS), multifocal acquired demyelinating sensory and motor neuritis (MADSAM), and associated central nervous system (CNS) demyelination. Misdiagnosis of CIDP occurs relatively frequently.

[0286] In some embodiments, subjects treated according to the methods described herein are diagnosed with CIDP using the official EFNS / PNS 2010 diagnostic criteria (Van den Bergh et al., 2010). In some embodiments, subjects are diagnosed with clear, possible CIDP. In some embodiments, subjects are diagnosed with possible CIDP.

[0287] The EFNS / PNS 2010 diagnostic criteria were revised in 2021, and refer to Van den Bergh et al., Eur J Neurol. 2021;28:3556 - 3583, and distinguish between "typical CIDP" and "CIDP variants" as defined in Table 8 below. CIDP variants were previously classified as "non - typical" forms of CIDP.

Table 8

[0288] Subjects treated according to the methods described herein may have typical CIDP. Typical CIDP typically begins with paresthesia and weakness in the distal extremities, as well as gait difficulty. Clinical examination shows progressive symmetric proximal and distal muscle weakness, sensory loss, and decreased or absent deep tendon reflexes.

[0289] Alternatively, subjects treated according to the methods described herein may have a CIDP variant form selected from the group consisting of distal CIDP, multifocal CIDP, focal CIDP, motor CIDP, and sensory CIDP. In certain embodiments, subjects treated according to the methods described herein have a CIDP variant form selected from the group consisting of distal CIDP, multifocal CIDP, focal CIDP, and motor CIDP. These CIDP variants are described in more detail below. - Distal CIDP, also known as "distal acquired demyelinating symmetric neuropathy" (DADS) or "distal symmetric disorder", this CIDP variant presents with sensory loss in the distal upper and lower extremities, as well as gait instability. Muscle weakness may occur and is usually more prominent distally in the lower extremities than in the upper extremities. Multifocal CIDP, also known as "multifocal demyelinating neuritis with persistent conduction block," "Lewis-Sumner syndrome" (LSS), "multifocal acquired demyelinating sensory and motor neuritis" (MADSAM), or multifocal inflammatory demyelinating neuritis, is a variant of CIDP that typically affects the upper extremities first and later the lower extremities. Cranial nerves are more frequently involved than in other forms of CIDP. - Focal CIDP. This variant is rare and usually affects the brachial or lumbosacral plexus, but may affect individual peripheral nerves. -Motor CIDP. This variant presents as relatively symmetrical proximal and distal weakness, but has clinically and electrodiagnostically normal sensation (in contrast to typical CIDP, where sensation is abnormal). - Sensory CIDP. This variant is typically characterized by gait ataxia, vibration and proprioceptive impairment, and altered cutaneous sensation. Muscle weakness is absent.

[0290] Furthermore, CIDP may be classified as "progressive" or "recurrent" at the time of diagnosis. In certain embodiments, the subject treated according to the method herein has progressive CIDP. In certain embodiments, the subject treated according to the method herein has recurrent CIDP.

[0291] In some cases, nodular and paranodal autoantibodies have been identified in patients with CIDP. These antibodies include anti-NF155 antibody (Cortese et al., 2020), anti-CNTN1 antibody (Querol et al., 2013), anti-Caspr1 antibody (Pascual-Goni et al., 2021), and anti-NF140 / 186 antibody (Delmont et al., 2017).

[0292] In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-NF155 antibodies. In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-CNTN1 antibodies. In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-Caspr1 antibodies. In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-NF140 / 186 antibodies.

[0293] In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-GM1 antibodies. In some embodiments, the subjects treated according to the method herein are CIDP patients characterized by the presence of anti-LM1 antibodies.

[0294] Subjects having CIDP treated according to the methods described herein may have mild, moderate, or severe CIDP.

[0295] In some embodiments, the subjects treated according to the methods herein are adults. In some embodiments, the subjects treated according to the methods herein are adults in the range of approximately 20 to approximately 82 years of age. In some embodiments, the subjects treated according to the methods herein are adults in the range of 20 to 82 years of age. The severity of CIDP disease in the subjects may be assessed using any of the assessment methods described herein, including, but not limited to, (i) INCAT disability scale (Merkies et al., 2002), (ii) MRC scale (Vanhoutte et al., 2012), (iii) I-RODS (van Nes et al., 2011), (iv) mean grip strength test (Vanhoutte et al., 2013), and (v) TUG test.

[0296] In certain embodiments, the severity of CIDP disorder is assessed using the INCAT disability scale, an FDA-approved scale for assessing the severity of motor impairment. The INCAT scale, described elsewhere in this specification, is a 10-point scale covering leg and arm function. Arm impairment scores range from 0 to 5, and leg impairment scores also range from 0 to 5 (0 being normal, and 5 being the most impaired). The total INCAT score is the sum of the arm and leg scores, ranging from 0 to 10. In certain embodiments, CIDP symptoms are assessed using the aINCAT score. According to the aINCAT score, changes in arm function from 0 (normal) to 1 (mild symptoms) or from 1 to 0 are not recorded as exacerbations or improvements, as these small changes are not considered clinically significant.

[0297] In certain embodiments, subjects treated according to the method described herein have a baseline INCAT score of 2 or higher, optionally 3 or higher, optionally 4 or higher, optionally 5 or higher, optionally 6 or higher, optionally 7 or higher, optionally 8 or higher, optionally 9 or higher, or optionally 10 (i.e., before treatment with an FcRn antagonist). In certain embodiments, subjects have a baseline INCAT score of 2, 3, 4, or 5, and the impairment is limited to the arm. In certain embodiments, subjects have a baseline INCAT score of 2, 3, 4, or 5, and the impairment is limited to the leg. In certain embodiments, subjects have a baseline INCAT score of 2, 3, 4, or 5, and the impairment affects both the arm and the leg. In certain embodiments, subjects have a baseline INCAT score of 5, and the impairment affects the arm, leg, or both. In some embodiments, subjects have a baseline INCAT score of 3, and the impairment affects the arm, leg, or both.

[0298] In certain embodiments, the severity of CIDP disease is assessed using the I-RODS. As described elsewhere herein, the I-RODS is a 24-item scale, each item representing a common daily activity ranging from very difficult activities such as running or dancing to very easy activities such as eating or reading a book. A higher score indicates less impairment. Raw I-RODS scores (range: 0-48) are typically converted to centile metric scores ranging from 0 (most severe activity and social participation limitations) to 100 (no activity or social participation limitations). In certain embodiments, subjects treated according to the method herein have baseline I-RODS centile metric scores of 10 or higher, optionally 20 or higher, optionally 30 or higher, optionally 40 or higher, and optionally 50 or higher. In certain embodiments, subjects treated according to the method herein have a baseline I-RODS centile metric score of 37.

[0299] In some embodiments, the severity of CIDP disease is assessed using a mean grip strength test. Mean grip strength can be measured using a handheld Martin dynamometer or a Jamar handgrip dynamometer. In some embodiments, subjects treated according to the method herein have a baseline mean grip strength of 20 kPa or greater, optionally 30 kPa or greater (when measured using the dominant hand). In some embodiments, subjects treated according to the method herein have a baseline mean grip strength of 1–100 kPa, optionally 10–90 kPa, optionally 20–80 kPa, optionally 30–70 kPa, or optionally 30–50 kPa.

[0300] In some embodiments, the subject treated according to the method described herein has newly diagnosed CIDP.

[0301] In some embodiments, subjects treated according to the method herein have CIDP diagnosed approximately two years prior to treatment with an FcRn antagonist. In some embodiments, subjects treated according to the method herein have CIDP diagnosed approximately 2.2 years prior to treatment with an FcRn antagonist. In some embodiments, subjects treated according to the method herein have CIDP diagnosed two years prior to treatment with an FcRn antagonist. In some embodiments, subjects treated according to the method herein have CIDP diagnosed 2.2 years prior to treatment with an FcRn antagonist.

[0302] In some embodiments, the subjects have relapsing CIDP. In some embodiments, the subjects have CIDP that is unstable and refractory to treatment, for example, CIDP characterized by a CIDP disease activity score (CDAS) of 5B or 5C.

[0303] In some embodiments, subjects treated according to the methods described herein are treatment-naïve. Subjects classified as “treatment-naïve” may have never received treatment for CIDP before. Subjects classified as “treatment-naïve” may also include subjects who have previously received treatment for CIDP but have not received treatment for CIDP in the six months prior to treatment with the FcRn antagonist described herein.

[0304] In some embodiments, subjects treated according to the method herein have previously received one or more treatments for CIDP, including but not limited to corticosteroids, IVIg, SCIg, plasma exchange, or other immunosuppressive treatments. In some embodiments, subjects treated according to the method herein have been previously treated with IVIg. In some embodiments, subjects treated according to the method herein have been previously treated with corticosteroids. In some embodiments, subjects treated according to the method herein have active disease despite treatment with corticosteroids or immunoglobulins.

[0305] Dosage In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 20 mg to approximately 20,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 200 mg to approximately 20,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 300 mg to approximately 6,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 750 mg to approximately 3,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 1,000 mg to approximately 2,500 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 1,000 mg to approximately 2,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 1,000 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0306] In some embodiments, the FcRn antagonist is administered in a fixed dose of 20 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 200 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 300 mg to 6,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 750 mg to 3,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 1,000 mg to 2,500 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 1,000 mg to 2,000 mg. In some embodiments, the FcRn antagonist is administered in a fixed dose of 1,000 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0307] In some embodiments, the FcRn antagonist is administered in a fixed dose of approximately 20 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg. In some embodiments, the FcRn antagonist is Evgarchigimodo.

[0308] In some embodiments, the FcRn antagonist is administered in fixed doses of 20 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0309] In some embodiments, the FcRn antagonist is administered in doses of approximately 0.2 mg / kg to approximately 200 mg / kg. In some embodiments, the FcRn antagonist is administered in doses of approximately 2 mg / kg to approximately 200 mg / kg. In some embodiments, the FcRn antagonist is administered in doses of approximately 2 mg / kg to approximately 120 mg / kg. In some embodiments, the FcRn antagonist is administered in doses of approximately 3 mg / kg to approximately 60 mg / kg. In some embodiments, the FcRn antagonist is administered in doses of approximately 10 mg / kg to approximately 25 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0310] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of approximately 2 mg / kg to approximately 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 2 mg / kg to 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 3 mg / kg to 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0311] In some cases, the FcRn antagonist is present in doses of approximately 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, and 45 mg / kg. It is administered in doses of approximately 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, 110 mg / kg, 120 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 170 mg / kg, 180 mg / kg, 190 mg / kg, or 200 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0312] In some embodiments, the FcRn antagonist is present in doses of 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, It is administered in doses of 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, 110 mg / kg, 120 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 170 mg / kg, 180 mg / kg, 190 mg / kg, or 200 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0313] In some embodiments, the FcRn antagonist is administered subcutaneously. In some embodiments, the FcRn antagonist is administered subcutaneously once a week. In some embodiments, the FcRn antagonist is administered subcutaneously once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgaltigimod.

[0314] In some embodiments, the FcRn antagonist is administered subcutaneously in a fixed dose of approximately 20 mg to approximately 20,000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously in a fixed dose of approximately 100 mg to approximately 10,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously in a fixed dose of 750 mg to 3000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgultigimod.

[0315] In some embodiments, the FcRn antagonist is present in doses of approximately 20 mg, 50 mg, 100 mg, 250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, and 11,000 mg. It is administered subcutaneously in fixed doses of mg, approximately 12,000 mg, approximately 13,000 mg, approximately 14,000 mg, approximately 15,000 mg, approximately 16,000 mg, approximately 17,000 mg, approximately 18,000 mg, approximately 19,000 mg, or approximately 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgultigimod.

[0316] In some embodiments, the FcRn antagonist is administered subcutaneously in fixed doses of 20 mg, 50 mg, 100 mg, 250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgultigimod.

[0317] In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of approximately 750 mg to approximately 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of approximately 1000 mg to approximately 2000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of approximately 1000 mg or approximately 2000 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0318] In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of 1000 mg to 2000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or every two weeks at a fixed dose of 1000 mg or 2000 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0319] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1000 mg. In some embodiments, efgultigimod is administered subcutaneously once a week at a fixed dose of approximately 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once every two weeks at a fixed dose of approximately 1000 mg. In some embodiments, efgultigimod is administered subcutaneously once every two weeks at a fixed dose of approximately 1000 mg.

[0320] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of approximately 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is efgaltigimod.

[0321] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of approximately 2000 mg for the first two doses, and then at a fixed dose of approximately 1000 mg thereafter. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 2000 mg for the first two doses, and then at a fixed dose of 1000 mg thereafter. In some embodiments, the first two doses of the FcRn antagonist are subcutaneous administrations of a fixed dose of approximately 1000 mg, administered twice on the same day. In some embodiments, the first two doses of the FcRn antagonist are subcutaneous administrations of a fixed dose of 1000 mg, administered twice on the same day. In some embodiments, the FcRn antagonist is efgaltigimod.

[0322] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 750 mg to approximately 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 800 mg to approximately 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1500 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1750 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0323] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 750 mg to 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 800 mg to 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1500 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1750 mg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0324] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1008 mg. In some embodiments, the FcRn antagonist is efgultigimod.

[0325] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of approximately 10 mg / kg to approximately 25 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of approximately 10 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of approximately 15 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of approximately 20 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of approximately 25 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0326] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 10 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 15 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 20 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 25 mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0327] In some embodiments, the FcRn antagonist is administered intravenously. In some embodiments, the FcRn antagonist is administered intravenously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgultigimod.

[0328] In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 0.2 mg / kg to approximately 200 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 2 mg / kg to approximately 200 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 2 mg / kg to approximately 120 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 3 mg / kg to approximately 60 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 10 mg / kg to approximately 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is Evgarchigimodo.

[0329] In some cases, the FcRn antagonist is present in doses of approximately 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, and 5 mg / kg. It is administered intravenously once a week or once every two weeks at doses of 5 mg / kg, approximately 60 mg / kg, approximately 65 mg / kg, approximately 70 mg / kg, approximately 75 mg / kg, approximately 80 mg / kg, approximately 85 mg / kg, approximately 90 mg / kg, approximately 95 mg / kg, approximately 100 mg / kg, approximately 110 mg / kg, approximately 120 mg / kg, approximately 130 mg / kg, approximately 140 mg / kg, approximately 150 mg / kg, approximately 160 mg / kg, approximately 170 mg / kg, approximately 180 mg / kg, approximately 190 mg / kg, or approximately 200 mg / kg. In some embodiments, the FcRn antagonist is fgaltigimod.

[0330] In some embodiments, the FcRn antagonist is present in doses of 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, and 55 mg / kg. It is administered intravenously once a week or once every two weeks in doses of g / kg, 60mg / kg, 65mg / kg, 70mg / kg, 75mg / kg, 80mg / kg, 85mg / kg, 90mg / kg, 95mg / kg, 100mg / kg, 110mg / kg, 120mg / kg, 130mg / kg, 140mg / kg, 150mg / kg, 160mg / kg, 170mg / kg, 180mg / kg, 190mg / kg, or 200mg / kg. In some embodiments, the FcRn antagonist is efgaltigimod.

[0331] In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 10 mg / kg to approximately 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 10 mg / kg to approximately 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 10 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 15 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 20 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of approximately 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 15 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 20 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is efgaltigimod.

[0332] In some embodiments, the FcRn antagonist is administered intravenously first, followed by subcutaneous administration. In some embodiments, the FcRn antagonist is administered intravenously first, followed by subcutaneous administration at a fixed dose of 100 mg to 10,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered intravenously first, followed by subcutaneous administration at a fixed dose of 1,000 mg or 2,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgaltigimod.

[0333] In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subsequent doses of the FcRn antagonist subcutaneously. In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subsequent doses of the FcRn antagonist in a fixed dose of 100 mg to 10,000 mg, administered subcutaneously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subsequent doses of the FcRn antagonist in a fixed dose of 1,000 mg or 2,000 mg, administered subcutaneously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is Evgarchigimodo.

[0334] In some embodiments, the FcRn antagonist is initially administered by a healthcare professional or under the supervision of a healthcare professional for at least five doses. In some embodiments, subsequent doses of efgaltigimod PH20 at clinically proven safe and effective doses are administered by a healthcare professional or by the patient or caregiver.

[0335] In some embodiments, the FcRn antagonist is administered for a period of 61 weeks or less, 52 weeks or less, or 48 weeks or less. In some embodiments, the FcRn antagonist is administered for at least 4 weeks. In some embodiments, the FcRn antagonist is administered for at least 12 weeks. In some embodiments, the FcRn antagonist is administered for at least 48 weeks. In some embodiments, the FcRn antagonist is administered for at least 52 weeks. In some embodiments, the FcRn antagonist is administered for at least 61 weeks.

[0336] In some embodiments, the FcRn antagonist is administered once a week until disease control or complete remission is achieved.

[0337] In some embodiments, the FcRn antagonist is administered during the induction phase and the subsequent maintenance phase. In certain embodiments, during the induction phase, the FcRn antagonist is administered once a week, and during the maintenance phase, the FcRn antagonist administration interval is extended to, for example, once every two weeks, once every three weeks, or once every four weeks. In embodiments in which the induction phase involves administration of the FcRn antagonist at a higher dose or dosing frequency than during the maintenance phase, any of the specific dosing regimens described herein may be applied during both the induction and maintenance phases.

[0338] For example, in certain embodiments, the FcRn antagonist is administered subcutaneously once a week during the induction phase and once every two weeks during the maintenance phase. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1000 mg during the induction phase and once every two weeks at a fixed dose of approximately 1000 mg during the maintenance phase. In some embodiments, the FcRn antagonist is efgultigimod. In some embodiments, the FcRn antagonist is self-administered during the maintenance phase.

[0339] The induction period may be at least 4 weeks, at least 8 weeks, or at least 12 weeks. The induction period may be 61 weeks or less, 52 weeks or less, or 48 weeks or less. The induction period may be 4 weeks to 61 weeks, 8 weeks to 52 weeks, or 12 weeks to 48 weeks. In some embodiments, the induction period ends, for example, based on clinical evaluation by a healthcare provider. In some embodiments, the induction period ends when the subject shows ECI.

[0340] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of approximately 1000 mg once weekly, and then, based on clinical evaluation, at a fixed dose of approximately 1000 mg once every two weeks. In some embodiments, the clinical evaluation is performed by the healthcare provider. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of approximately 1000 mg once weekly, and then, when an ECI is demonstrated in the subject, at a fixed dose of approximately 1000 mg once every two weeks. In some embodiments, weekly subcutaneous administration at a fixed dose of approximately 1000 mg is resumed in response to symptom exacerbation.

[0341] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1000 mg once weekly, and then, based on clinical evaluation, subcutaneously at a fixed dose of 1000 mg once every two weeks. In some embodiments, clinical evaluation is performed by the healthcare provider. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1000 mg once weekly, and then, when an ECI is demonstrated in the subject, subcutaneously at a fixed dose of 1000 mg once every two weeks. In some embodiments, subcutaneous administration at a fixed dose of 1000 mg once weekly is resumed in response to symptom exacerbation.

[0342] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1008 mg once weekly, and then, based on clinical evaluation, subcutaneously at a fixed dose of 1008 mg once every two weeks. In some embodiments, clinical evaluation is performed by the healthcare provider. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1008 mg once weekly, and then, when an ECI is demonstrated in the subject, subcutaneously at a fixed dose of 1008 mg once every two weeks. In some embodiments, subcutaneous administration at a fixed dose of 1008 mg once weekly is resumed in response to symptom exacerbation.

[0343] In some embodiments, a period of time follows treatment with one of the drug regimens described herein in which the subject does not receive further FcRn antagonist treatment. Subjects receiving an FcRn antagonist with one of the drug regimens described herein may achieve disease activity control (CDA), partial remission (PR), or complete remission (CR) so that they may be able to discontinue treatment. Subjects may remain treatment-naive during the period in which CDA, PR, or CR is achieved, and optionally receive further treatment if clinical exacerbations occur. If CDA, PR, or CR is not achieved or a relapse occurs following further treatment with one of the drug regimens described herein, the subject may receive further treatment with an FcRn antagonist with one of the drug regimens described herein.

[0344] In some embodiments, the FcRn antagonist is administered subcutaneously once a week for at least 4 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously once a week until the subject shows an ECI. In some embodiments, the FcRn antagonist is administered once a week until the subject shows an ECI during two consecutive measurements, optionally performed approximately one week apart. In some embodiments, the FcRn antagonist is administered subcutaneously once a week until the subject shows two ECIs in two weeks. In some embodiments, the ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, INCAT, or aINCAT score. In some embodiments, the ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, or INCAT score.

[0345] In some embodiments, an FcRn antagonist is administered subcutaneously once a week until the subject exhibits an ECMD. In some embodiments, an ECMD is one or more of the following: an increase of 1 or more points in the aINCAT score, a decrease of 4 or more points in I-RODS (using centile metrics), or a decrease of 8 kPa or more in average grip strength in one hand using a handheld dynamometer. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score during two consecutive measurements, optionally taken at intervals of approximately one week. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score during two consecutive measurements over two weeks. In some embodiments, an ECMD is an increase of 2 or more points in the aINCAT score.

[0346] In some embodiments, efgultigimod PH20 in a clinically proven safe and effective dose is administered subcutaneously. In some embodiments, efgultigimod PH20 in a clinically proven safe and effective dose is administered subcutaneously once a week or once every two weeks. In some embodiments, efgultigimod PH20 in a clinically proven safe and effective dose is administered subcutaneously once a week. In some embodiments, efgultigimod PH20 in a clinically proven safe and effective dose is administered subcutaneously once a week for at least four weeks. In some embodiments, efgultigimod PH20 in a clinically proven safe and effective dose is administered subcutaneously once a week until the subject shows eclocytic infection (ECI). In some embodiments, a clinically proven safe and effective dose of efgultigimod PH20 is administered once a week until the subject shows an ECI during two consecutive measurements, optionally performed approximately one week apart. In some embodiments, a clinically proven safe and effective dose of efgultigimod PH20 is administered subcutaneously once a week until the subject shows an ECI twice over two weeks. In some embodiments, the ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, INCAT, or aINCAT score. In some embodiments, the ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, or INCAT score.

[0347] In some embodiments, a clinically proven safe and effective dose of efgaltigimod PH20 is administered subcutaneously once a week until the subject exhibits an ECMD. In some embodiments, an ECMD is one or more of the following: an increase of 1 or more points in the aINCAT score, a decrease of 4 or more points in I-RODS (using centile metrics), or a decrease of 8 kPa or more in average grip strength in one hand using a handheld dynamometer. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score during two consecutive measurements, optionally, taken approximately one week apart. In some embodiments, an ECMD is an increase of 1 or more points in the aINCAT score during two consecutive measurements over two weeks. In some embodiments, an ECMD is an increase of 2 or more points in the aINCAT score.

[0348] In some embodiments, a clinically proven safe and effective dose of efgaltigimod PH20 is initially administered subcutaneously once a week, and then subcutaneously every two weeks based on clinical evaluation. In some embodiments, clinical evaluation is performed by the healthcare provider. In some embodiments, a clinically proven safe and effective dose of efgaltigimod PH20 is initially administered subcutaneously once a week, and then subcutaneously every two weeks when an ECI is demonstrated in the subject. In some embodiments, weekly subcutaneous administration of a clinically proven safe and effective dose of efgaltigimod PH20 is resumed in response to symptom exacerbation. In some embodiments, a clinically proven safe and effective dose of efgaltigimod PH20 is administered subcutaneously over approximately 30 to 90 seconds. In some embodiments, a clinically proven safe and effective dose of efgartigimod PH20 is initially administered by a healthcare professional or under the supervision of a healthcare professional for at least five doses. In some embodiments, subsequent doses of a clinically proven safe and effective dose of efgartigimod PH20 are administered by a healthcare professional or by the patient or caregiver.

[0349] In some embodiments, the dose of efgartigimod PH20 that has been proven clinically safe and effective is 1008 mg / 11,200 units. In some embodiments, the dose of efgartigimod PH20 that has been proven clinically safe and effective is 1000 mg / 11,200 units.

[0350] In some embodiments, the FcRn antagonist is rozanolixizumab. In some embodiments, rozanolixizumab is administered subcutaneously or intravenously. In some embodiments, rozanolixizumab is administered in doses ranging from approximately 0.2 mg / kg to approximately 200 mg / kg, or in fixed doses ranging from approximately 20 mg to approximately 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0351] In some cases, rozanolixizumab is available in doses of approximately 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 12.5 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, and 25 mg / kg. g / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39mg / kg, approximately 40mg / kg, approximately 41mg / kg, approximately 42mg / kg, approximately 43mg / kg, approximately 44mg / kg, approximately 45mg / kg, approximately 46mg / kg, approximately 47mg / kg, approximately 48mg / kg, approximately 49mg / kg, approximately 50mg / kg, approximately 51mg / kg, approximately 52mg / k g, approximately 53mg / kg, approximately 54mg / kg, approximately 55mg / kg, approximately 56mg / kg, approximately 57mg / kg, approximately 58mg / kg, approximately 59mg / kg, approximately 60mg / kg, approximately 61mg / kg, approximately 62mg / kg, approximately 63mg / kg, approximately 64mg / kg, approximately 65mg / kg, approximately 66m g / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 77mg / kg, about 78mg / kg, about 79mg / kg, about It is administered in doses of 80 mg / kg, approximately 81 mg / kg, approximately 82 mg / kg, approximately 83 mg / kg, approximately 84 mg / kg, approximately 85 mg / kg, approximately 86 mg / kg, approximately 87 mg / kg, approximately 88 mg / kg, approximately 89 mg / kg, approximately 90 mg / kg, approximately 91 mg / kg, approximately 92 mg / kg, approximately 93 mg / kg, approximately 94 mg / kg, approximately 95 mg / kg, approximately 96 mg / kg, approximately 97 mg / kg, approximately 98 mg / kg, approximately 99 mg / kg, or approximately 100 mg / kg, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

[0352] In some embodiments, the FcRn antagonist is nipocalimab. In some embodiments, nipocalimab is administered subcutaneously or intravenously. In some embodiments, nipocalimab is administered in doses ranging from approximately 0.2 mg / kg to approximately 200 mg / kg, or in fixed doses ranging from approximately 20 mg to approximately 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0353] In some cases, nipocalimab is available in doses of approximately 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 12.5 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, and 25 mg / kg. g, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, approximately 40 mg / kg, approximately 41 mg / kg, approximately 42 mg / kg, approximately 43 mg / kg, approximately 44 mg / kg, approximately 45 mg / kg, approximately 46 mg / kg, approximately 47 mg / kg, approximately 48 mg / kg, approximately 49 mg / kg, approximately 50 mg / kg, approximately 51 mg / kg, approximately 52 mg / kg, Approximately 53mg / kg, approximately 54mg / kg, approximately 55mg / kg, approximately 56mg / kg, approximately 57mg / kg, approximately 58mg / kg, approximately 59mg / kg, approximately 60mg / kg, approximately 61mg / kg, approximately 62mg / kg, approximately 63mg / kg, approximately 64mg / kg, approximately 65mg / kg, approximately 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 77mg / kg, about 78mg / kg, about 79mg / kg, about 8 It is administered at doses of 0 mg / kg, approximately 81 mg / kg, approximately 82 mg / kg, approximately 83 mg / kg, approximately 84 mg / kg, approximately 85 mg / kg, approximately 86 mg / kg, approximately 87 mg / kg, approximately 88 mg / kg, approximately 89 mg / kg, approximately 90 mg / kg, approximately 91 mg / kg, approximately 92 mg / kg, approximately 93 mg / kg, approximately 94 mg / kg, approximately 95 mg / kg, approximately 96 mg / kg, approximately 97 mg / kg, approximately 98 mg / kg, approximately 99 mg / kg, or approximately 100 mg / kg, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

[0354] In some embodiments, the FcRn antagonist is olilanorimab. In some embodiments, olilanorimab is administered subcutaneously or intravenously. In some embodiments, olilanorimab is administered in doses ranging from approximately 0.2 mg / kg to approximately 200 mg / kg, or in fixed doses ranging from approximately 20 mg to approximately 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0355] In some cases, olilanorimab is available in doses of approximately 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 12.5 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, and 25 mg. / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg, about 38mg / kg, about 39mg / kg, approximately 40mg / kg, approximately 41mg / kg, approximately 42mg / kg, approximately 43mg / kg, approximately 44mg / kg, approximately 45mg / kg, approximately 46mg / kg, approximately 47mg / kg, approximately 48mg / kg, approximately 49mg / kg, approximately 50mg / kg, approximately 51mg / kg, approximately 52mg / k g, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about 77 mg / kg, about 78 mg / kg, about 79 mg / kg It is administered in doses of approximately 80 mg / kg, 81 mg / kg, 82 mg / kg, 83 mg / kg, 84 mg / kg, 85 mg / kg, 86 mg / kg, 87 mg / kg, 88 mg / kg, 89 mg / kg, 90 mg / kg, 91 mg / kg, 92 mg / kg, 93 mg / kg, 94 mg / kg, 95 mg / kg, 96 mg / kg, 97 mg / kg, 98 mg / kg, 99 mg / kg, or 100 mg / kg, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

[0356] In some embodiments, olilanorimab is administered intravenously at a dose of approximately 30 mg / kg once a week for three weeks, followed by intravenous administration at a dose of 10 mg / kg every other week.

[0357] In some embodiments, the FcRn antagonist is batoclimab or IMVT-1402. In some embodiments, batoclimab or IMVT-1402 is administered subcutaneously or intravenously. In some embodiments, batoclimab or IMVT-1402 is administered in doses of approximately 0.2 mg / kg to approximately 200 mg / kg, or in fixed doses of approximately 20 mg to approximately 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0358] In some applications, batoclimab or IMVT-1402 is administered at approximately 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 12.5 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, and 24 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / kg, about 51mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, about 64 mg / kg, about 65 mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 77mg / kg, about 78mg / kg, about 79mg / kg It is administered in doses of approximately 80 mg / kg, 81 mg / kg, 82 mg / kg, 83 mg / kg, 84 mg / kg, 85 mg / kg, 86 mg / kg, 87 mg / kg, 88 mg / kg, 89 mg / kg, 90 mg / kg, 91 mg / kg, 92 mg / kg, 93 mg / kg, 94 mg / kg, 95 mg / kg, 96 mg / kg, 97 mg / kg, 98 mg / kg, 99 mg / kg, or 100 mg / kg, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

[0359] Treatment Outcomes Treatment of CIDP typically results in a change, specifically improvement, in the disease state. In some embodiments, administration of an FcRn antagonist to a subject with CIDP results in control of disease activity (CDA), partial remission (PR), or complete remission (CR) as defined herein. In some embodiments, complete remission is achieved. In some embodiments, the CDA, PR, or CR lasts in the subject for at least two months, at least three months, at least four months, at least five months, or at least six months.

[0360] In some embodiments, CDA, PR, or CR is achieved within 12 weeks of first receiving the FcRn antagonist described herein. In some embodiments, CDA, PR, or CR is achieved within 8 weeks of first receiving the FcRn antagonist described herein. In some embodiments, CDA, PR, or CR is achieved within 6 weeks of first receiving the FcRn antagonist described herein. In some embodiments, CDA, PR, or CR is achieved within 4 weeks of first receiving the FcRn antagonist described herein. In some embodiments, CDA, PR, or CR is achieved within 3 weeks of first receiving the FcRn antagonist described herein. In some embodiments, the FcRn antagonist is evgarchigimodo.

[0361] In some embodiments, once CDA, PR, or CR is achieved, continuous administration of an FcRn antagonist prevents symptom exacerbation. This prevention may be achieved over the duration of treatment, i.e., the entire time the subject is receiving the FcRn antagonist. The absence of symptom exacerbation may be measured using any of the assessment methods described herein, including but not limited to: (i) INCAT disability scale (Merkies et al., 2002), (ii) MRC scale (Vanhoutte et al., 2012), (iii) I-RODS (van Nes et al., 2011), (iv) mean grip strength test (Vanhoutte et al., 2013), and (v) TUG test.

[0362] In certain embodiments, treatment with an FcRn antagonist achieves CDA, PR and / or CR, and / or prevents or delays relapse, i.e., clinical exacerbation of symptoms. In certain embodiments, disease relapse is prevented or delayed for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, and at least 20 weeks.

[0363] In some embodiments, the treatment prevents or delays CIDP relapse after achieving PR or CR from CIDP for at least 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, or 52 weeks.

[0364] In some embodiments, the treatment prevents or delays CIDP relapses over the course of treatment, i.e., there is no exacerbation of symptoms during the period the subject is receiving an FcRn antagonist.

[0365] In some embodiments, the treatment prevents or delays relapse during the period after discontinuation of treatment, i.e., after the subject stops receiving the FcRn antagonist. In some embodiments, the treatment prevents or delays relapse after discontinuation of treatment for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks. In some embodiments, the treatment prevents or delays relapse after discontinuation of treatment for at least 20 weeks.

[0366] In some embodiments, treatment-naive subjects are treated according to the methods described herein, and partial remission (PR) or complete remission is achieved. In these embodiments, subjects may experience prevention or delay of relapse over the course of treatment (if FcRn antagonist treatment is continued after PR or CR is achieved). For these embodiments, treatment-naive subjects may, alternatively or additionally, experience prevention or delay of relapse after discontinuation of treatment.

[0367] In some embodiments, the treatment reduces the risk of relapse by at least 60% compared to subjects not treated with an FcRn antagonist. In some embodiments, the treatment reduces the risk of relapse after discontinuation of treatment by at least 60% compared to subjects not treated with an FcRn antagonist. In some embodiments, the treatment reduces the risk of relapse by approximately 61% compared to subjects not treated with an FcRn antagonist. In some embodiments, the treatment reduces the risk of relapse after discontinuation of treatment by approximately 61% compared to subjects not treated with an FcRn antagonist. In some embodiments, the treatment reduces the risk of relapse by 61% compared to subjects not treated with an FcRn antagonist. In some embodiments, the treatment reduces the risk of relapse after discontinuation of treatment by 61% compared to subjects not treated with an FcRn antagonist.

[0368] In some embodiments, subjects treated according to the methods described herein exhibit improvement in one or more CIDP symptoms after administration of an FcRn antagonist. Symptom improvement may be assessed using any of the assessment methods described herein, including, but not limited to, (i) INCAT disability scale (Merkies et al., 2002), (ii) MRC scale (Vanhoutte et al., 2012), (iii) I-RODS (van Nes et al., 2011), (iv) mean grip strength test (Vanhoutte et al., 2013), and (v) TUG test. In some embodiments, improvement in one or more CIDP symptoms is achieved within 12 weeks from the first dose of the FcRn antagonist described herein. In some embodiments, improvement in one or more CIDP symptoms is achieved within 8 weeks from the first dose of the FcRn antagonist described herein. In some embodiments, improvement in one or more CIDP symptoms is achieved within 6 weeks from the first dose of the FcRn antagonist described herein. In some embodiments, improvement in one or more CIDP symptoms is achieved within 4 weeks of the first dose of the FcRn antagonist described herein. In some embodiments, improvement in one or more CIDP symptoms is achieved within 3 weeks of the first dose of the FcRn antagonist described herein. In some embodiments, improvement in one or more CIDP symptoms is achieved within 9 days of the first dose of the FcRn antagonist described herein. In some embodiments, improvement in at least one of the following—aINCAT score, I-RODS, or grip strength—is achieved within 9 days of first receiving the FcRn antagonist described herein.

[0369] In some embodiments, subjects treated according to the method herein show improvement in symptoms compared to baseline, i.e., before treatment, as measured using the INCAT disability scale. In some embodiments, subjects show a decrease of 1 or more in the INCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 1 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 2 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 3 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 4 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 5 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 6 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 7 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 8 or more in the aINCAT score (i.e., improvement). In some embodiments, subjects show a decrease of 9 or more in the aINCAT score (i.e., improvement).

[0370] In some embodiments, subjects show a decrease in aINCAT score after FcRn antagonist administration, such that the aINCAT score is ≤5, ≤4, ≤3, ≤2, or ≤1. Subjects may show improvements in upper limb function, lower limb function, or both, as measured using the aINCAT score.

[0371] In some embodiments, subjects treated according to the methods described herein show improvement in symptoms as measured using the MRC scale. As described elsewhere in this specification, the MRC scale is a 5-point scale (0-5), where 0 indicates complete paralysis and 5 indicates normal strength. This scale is applied bilaterally to six muscle groups of the upper and lower limbs to obtain a total score ranging from 0 to 60 (1. abductor brachii, 2. flexor elbow, 3. extensor wrist, 4. flexor hip, 5. extensor knee, and 6. dorsiflexor ankle). In some embodiments, subjects show an increase (i.e., improvement) in MRC scores of 2 or more, 3 or more, 5 or more, 10 or more, 20 or more, 30 or more, or 40 or more. Subjects may show improvement in upper limb function, lower limb function, or both as measured using the MRC scale.

[0372] In some embodiments, subjects treated according to the methods described herein show improvement in symptoms as measured using I-RODS. As described elsewhere herein, I-RODS is a 24-item scale, each item representing a common daily activity, ranging from very difficult activities such as running or dancing to very easy activities such as eating or reading a book. A higher score indicates less impairment. Raw I-RODS scores (range: 0-48) are typically converted to centile metric scores ranging from 0 (most severe activity and social participation limitations) to 100 (no activity or social participation limitations). In some embodiments, subjects show an increase (i.e., improvement) of 4 or more, 8 or more, 12 or more, or 20 or more in their I-RODS centile metric score.

[0373] In some embodiments, subjects treated according to the method described herein show improvement in symptoms as measured using an average grip strength test. Average grip strength can be measured using a handheld Martin dynamometer. In some embodiments, subjects show an increase in average grip strength of ≥8 kPa, ≥16 kPa, and ≥24 kPa after administration of an FcRn antagonist. Average grip strength is typically measured by testing the subject's dominant hand.

[0374] In some embodiments, subjects treated according to the methods described herein show improvement in symptoms as measured using the TUG test. The TUG test is a simple test used to assess human mobility and requires both static and dynamic balance. The TUG test measures the time it takes to stand up from a chair, walk 3 meters, turn around, return to the chair, and sit down. In some embodiments, subjects show improvement in the TUG test by a reduction of 5%, 10%, 15%, 20%, 25%, or 30% or more in the time it takes to complete the test.

[0375] In some embodiments, subjects demonstrate an improvement in quality of life (QoL) as measured according to one of the QoL scales / tests described herein. In some embodiments, QoL is assessed by one or more of the following: EuroQoL 5-dimensional 5-level (EQ-5D-5L), Brief Pain Inventory Short Form (BPI-SF), Treatment Satisfaction Questionnaire for Medication (TSQM-9) (9 items), Rush Transformation-Fatigue Severity Scale (RT-FSS), Hospital Anxiety Depression Scale (HADS), and Patient Global Impression Change (PGIC).

[0376] In some embodiments, subjects exhibit a decrease in serum levels of one or more of the following after administration of an FcRn antagonist: (i) total IgG levels, (ii) autoantibody levels, (iii) cytokine levels, (iv) chemokine levels, and (v) immune complexes. The decrease can be measured using any suitable technique known to those skilled in the art.

[0377] In some embodiments, subjects exhibit a decrease in serum levels of one or more autoantibodies after administration of an FcRn antagonist. Such autoantibodies may be selected from the group consisting of anti-GM1 antibodies, anti-LM-1 antibodies, anti-NF-155 antibodies, anti-CNTN1 antibodies, anti-Caspr-1 antibodies, and anti-myelinated nerve antibodies.

[0378] FcRn also binds to serum albumin, a regulator of serum cholesterol levels, and recirculates it. Certain FcRn antagonists, specifically certain anti-FcRn antibodies, have been found to lower serum albumin levels and therefore increase serum cholesterol levels in human subjects, both of which are undesirable.

[0379] In some embodiments, subjects treated according to the methods described herein do not experience a decrease in serum albumin levels after administration of an FcRn antagonist. In some embodiments, a decrease in serum albumin levels of less than 1%, 2%, 3%, 4%, or 5% compared to baseline albumin levels is observed. In one embodiment, a decrease in serum albumin levels of less than 10% compared to baseline albumin levels is observed. In some embodiments, subjects treated according to the methods described herein do not experience an increase in serum cholesterol levels after administration of an FcRn antagonist. In some embodiments, an increase in serum cholesterol levels of less than 1%, 2%, 3%, 4%, or 5% compared to baseline cholesterol levels is observed. In one embodiment, an increase in serum cholesterol levels of less than 10% compared to baseline cholesterol levels is observed. Serum cholesterol may be measured in the form of total cholesterol, high-density lipoprotein (HDL) cholesterol, and / or the total cholesterol:HDL ratio. Advantageously, fgultigimod does not decrease serum albumin levels. Therefore, in some embodiments, the FcRn antagonist is Evgarchigimodo.

[0380] In some embodiments, subjects treated according to the methods described herein do not experience significant proteinuria, i.e., significant or abnormal levels of protein in the urine. Proteinuria can be quantified by albumin / creatinine ratio (ACR) or protein / creatinine ratio (PCR). In some embodiments, subjects treated according to the methods described herein have an ACR of 15 mg / mmol or less, preferably 3 mg / mmol or less.

[0381] In some embodiments, subjects treated according to the methods described herein, particularly those receiving an FcRn antagonist via a subcutaneous administration route, experience minimal injection site reactions. Injection site reactions (ISRs) are well-characterized phenomena in the administration of pharmaceutical agents (e.g., biological agents) and include swelling, erythema, itching, and pain around the injection site.

[0382] In some embodiments, treatment according to the method herein exhibits a safety profile that eliminates the need for continuous monitoring of standard patient parameters, particularly those regularly monitored during treatment of CIDP patients. In some embodiments, treatment according to the method herein exhibits a safety profile that eliminates the need for continuous or periodic monitoring of serum albumin levels, serum cholesterol levels, and / or proteinuria. In some embodiments, treatment according to the method herein exhibits a safety profile that eliminates the need for patient premedication.

[0383] In some embodiments, methods are provided for treating CIDP in subjects in a patient population. In some embodiments, the method includes administering an FcRn antagonist as described herein to a subject in a patient population. In some embodiments, the method includes administering an FcRn antagonist as described herein, co-formulated with hyaluronidase, to a subject in a patient population. In some embodiments, the method includes administering efgultigimod PH20 or a biosimilar version thereof to a patient population. In some embodiments, the method includes administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof to a patient population. In some embodiments, the method includes subcutaneous administration of an FcRn antagonist (e.g., efgultigimod) once a week.

[0384] In some embodiments, the patient population exhibits ECI in 66.5% of subjects in the patient population. In some embodiments, the patient population exhibits ECI in 66.5% of subjects in the patient population after administration of an FcRn antagonist. In some embodiments, the patient population exhibits ECI in 66.5% of subjects in the patient population. In some embodiments, the patient population exhibits ECI in 66.5% of subjects in the patient population after administration of an FcRn antagonist. In some embodiments, the patient population achieves ECI within 31 to 51 days after initial FcRn antagonist administration. In some embodiments, the patient population achieves ECI within 43 days. In some embodiments, the patient population achieves ECI within 43 days after initial FcRn antagonist administration. In some embodiments, the patient population includes 322 subjects. In some embodiments, the FcRn antagonist is efgaltigimod PH20 or a biosimilar version thereof.

[0385] In some embodiments, the patient population shows evidence of improvement in 69% of subjects in the patient population during two consecutive measurements after administration of the FcRn antagonist. In some embodiments, evidence of improvement is selected from an improvement of 1 or more aINCAT points, an improvement of 4 or more I-RODS points, or an improvement of 8 kPa or more in average grip strength. In some embodiments, the patient population includes 322 subjects. In some embodiments, the FcRn antagonist is efgultigimod PH20 or a biosimilar version thereof.

[0386] In some embodiments, anti-fgultigimod alpha antibodies are detected in 6% of the target population after administration of an FcRn antagonist. In some embodiments, anti-fgultigimod alpha antibodies are detected in 6% of the target population for up to 12 weeks after administration of an FcRn antagonist. In some embodiments, neutralizing anti-fgultigimod alpha antibodies are detected in 0.3% of the target population after administration of an FcRn antagonist. In some embodiments, neutralizing anti-fgultigimod alpha antibodies are detected in 0.3% of the target population for up to 12 weeks after administration of an FcRn antagonist. In some embodiments, anti-fgultigimod alpha antibodies are detected in 2% of the target population after administration of an FcRn antagonist. In some embodiments, anti-fgultigimod alpha antibodies are detected in 2% of the target population for up to 48 weeks after administration of an FcRn antagonist. In some embodiments, the FcRn antagonist is efgalchigimod PH20 or a biosimilar version thereof.

[0387] In some embodiments, subjects in the patient population remain relapse-free for longer (e.g., significantly longer) than subjects who did not receive efgultigimod PH20 or its biosimilar version. In some embodiments, subjects in the patient population remain relapse-free from CIDP symptoms for longer (e.g., significantly longer) than subjects who did not receive efgultigimod PH20 or its biosimilar version.

[0388] In some embodiments, subjects in the patient population experience a longer time to clinical exacerbation compared to subjects who did not receive efgaltigimod PH20 or its biosimilar version. In some embodiments, clinical exacerbation is defined as an increase of one or more points in the aINCAT score. In some embodiments, clinical exacerbation is defined as an increase of one or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation is defined as an increase of two or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant.

[0389] In some embodiments, subjects in a patient population treated with efgaltigimod PH20 or its biosimilar version show a 61% reduction in the risk of exacerbation. In some embodiments, subjects in a patient population treated with efgaltigimod PH20 or its biosimilar version show a 61% reduction in the risk of exacerbation in patients with CIDP. In some embodiments, subjects in a patient population treated with efgaltigimod PH20 or its biosimilar version show a 61% reduction in the risk of exacerbation compared to subjects not treated with efgaltigimod PH20 (e.g., subjects treated with placebo).

[0390] In some embodiments, the mean percentage reduction in total IgG levels (e.g., serum IgG levels) from baseline in the patient population ranged from approximately 66.8% to approximately 71.6% after administration of efgartigimod PH20 or its biosimilar version. In some embodiments, the mean percentage reduction in total IgG levels (e.g., serum IgG levels) from baseline in the patient population ranged from approximately 66.8% to 71.6% after administration of efgartigimod PH20 or its biosimilar version. In some embodiments, the mean percentage reduction in total IgG levels (e.g., serum IgG levels) from baseline persisted from week 4 throughout the treatment period.

[0391] In some embodiments, subjects show a decrease of approximately 66.8% to approximately 71.6% in serum total IgG levels after administration of efgultigimod PH20 or its biosimilar version. In some embodiments, subjects show a decrease of approximately 66.8% to approximately 71.6% in serum total IgG levels after administration of efgultigimod PH20 or its biosimilar version once a week for a total of four doses. In some embodiments, subjects show a decrease of 66.8% to approximately 71.6% in serum total IgG levels after administration of efgultigimod PH20 or its biosimilar version. In some embodiments, subjects show a decrease of 66.8% to 71.6% in serum total IgG levels after administration of efgultigimod PH20 or its biosimilar version once a week for a total of four doses. In some embodiments, the decrease in serum total IgG levels persists until the once-weekly administration of efgultigimod PH20 or its biosimilar version is discontinued.

[0392] In some embodiments, prior to treatment with efgaltigimod PH20, the patient population includes treatment-naïve CIDP patients, CIDP patients receiving immunoglobulins, and CIDP patients receiving corticosteroids.

[0393] In some embodiments, the patient population includes patients with CIDP that is unstable and refractory to treatment (CIDP Disease Activity Score (CDAS) 5B and 5C) prior to treatment with efgartigimod PH20, as well as patients with CIDP that is stable with existing treatments (CDAS 3 and 4) prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with mild to severe impairment prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with INCAT scores of 2 to 9 prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with IRODS scores of 11 to 61 prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with an average grip strength of 1 to 120 kPa prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with an average INCAT score of 5 prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with an average IRODS of 37 prior to treatment with efgartigimod PH20. In some embodiments, the patient population includes CIDP patients with an average grip strength of 39 kPa prior to treatment with efgartigimod PH20.

[0394] Additional treatments The methods described herein may include an additional step of administering to a subject an effective amount of one or more additional therapeutic agents.

[0395] In some embodiments, the method further comprises administering an effective amount of one or more immunosuppressants. Examples include, but are not limited to, methotrexate, mycophenolate mofetil (MMF), azathioprine, cyclophosphamide, doxycycline, and dapsone.

[0396] In some embodiments, the method further comprises administering an effective amount of one or more corticosteroids to a subject. In certain embodiments, the corticosteroid is an oral corticosteroid. Examples of oral corticosteroids, but not limited to, include betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, and triamcinolone. In some embodiments, the oral corticosteroid is dexamethasone. In some embodiments, the oral corticosteroid is methylprednisolone, prednisone, or prednisolone.

[0397] In one embodiment, an effective dose of corticosteroid is administered at a dose of 2.5 mg / day to 20 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of 5 mg / day to 20 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of 7.5 mg / day to 20 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of 8 mg / day to 15 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of 10 mg / day to 15 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 20 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 10 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 7.5 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 5 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 2.5 mg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 1 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.75 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.5 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.4 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.3 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.25 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.2 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.15 mg / kg / day. In one embodiment, an effective dose of corticosteroid is administered at a dose of approximately 0.1 mg / kg / day.

[0398] Patients treated with corticosteroids may have their corticosteroid regimen tapered before, during, or after treatment with an FcRn antagonist. Tapering a corticosteroid regimen may mean reducing the dose of corticosteroids or reducing the frequency of administration.

[0399] In one embodiment, the dose of corticosteroids is reduced after CDA or remission (partial or complete) is achieved. In some embodiments, the dose of corticosteroids is reduced after CDA has lasted for at least two weeks.

[0400] In some embodiments, corticosteroid dosage regimens are reduced by following a tapering schedule. Examples of tapering schedules that may be used to reduce corticosteroid dosage are provided herein. It will be understood by those skilled in the art that tapering schedules may vary and be adapted depending on several subject-specific factors, such as the initial corticosteroid dose, changes in CIDP symptoms, and the subject's overall health.

[0401] In some embodiments, the daily dose of an oral corticosteroid (OCS), such as prednisone, is reduced from 0.5 mg / kg / day to 0.3 mg / kg / day, from 0.3 mg / kg / day to 0.2 mg / kg / day, from 0.2 mg / kg / day to 0.15 mg / kg / day, and from 0.15 mg / kg / day to 0.1 mg / kg / day. In some embodiments, each daily dose of the OCS, such as prednisone, is maintained for at least two weeks before the dose is further reduced. In some embodiments, the daily dose of the OCS, such as prednisone, is maintained at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, and then at 0.1 mg / kg / day for at least two weeks. In some embodiments, the daily dose of the OCS, for example, prednisone, is maintained at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, and then at 0.1 mg / kg / day for at least eight weeks. In some embodiments, each daily dose is optionally maintained for two weeks unless CIDP symptoms worsen.

[0402] In some embodiments, the daily dose of OCS, e.g., prednisone, is reduced from 0.75 mg / kg / day to 0.5 mg / kg / day, from 0.5 mg / kg / day to 0.3 mg / kg / day, from 0.3 mg / kg / day to 0.2 mg / kg / day, from 0.2 mg / kg / day to 0.15 mg / kg / day, and from 0.15 mg / kg / day to 0.1 mg / kg / day. In some embodiments, each daily dose of OCS, e.g., prednisone, is maintained for at least two weeks before the dose is further reduced. In some embodiments, the daily dose of OCS, e.g., prednisone, is maintained at 0.5 mg / kg / day for at least two weeks, then at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, and then at 0.1 mg / kg / day for at least two weeks. In some embodiments, the daily dose of the OCS, for example, prednisone, is maintained at 0.5 mg / kg / day for at least two weeks, then at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, and then at 0.1 mg / kg / day for at least eight weeks. In some embodiments, each daily dose is optionally maintained for two weeks unless CIDP symptoms worsen.

[0403] In some embodiments, the daily dose of OCS, e.g., prednisone, is reduced from 1 mg / kg / day to 0.75 mg / kg / day, from 0.75 mg / kg / day to 0.5 mg / kg / day, from 0.5 mg / kg / day to 0.3 mg / kg / day, from 0.3 mg / kg / day to 0.2 mg / kg / day, from 0.2 mg / kg / day to 0.15 mg / kg / day, and from 0.15 mg / kg / day to 0.1 mg / kg / day. In some embodiments, each daily dose of OCS, e.g., prednisone, is maintained for at least two weeks before the dose is further reduced. In some embodiments, the daily dose of the OCS, e.g., prednisone, is maintained at 0.75 mg / kg / day for at least two weeks, then at 0.5 mg / kg / day for at least two weeks, then at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, then at 0.1 mg / kg / day for at least two weeks. In some embodiments, the daily dose of the OCS, e.g., prednisone, is maintained at 0.75 mg / kg / day for at least two weeks, then at 0.5 mg / kg / day for at least two weeks, then at 0.3 mg / kg / day for at least two weeks, then at 0.2 mg / kg / day for at least two weeks, then at 0.15 mg / kg / day for at least two weeks, then at 0.1 mg / kg / day for at least eight weeks. In some embodiments, each daily dose is optionally maintained for two weeks unless CIDP symptoms worsen.

[0404] After maintenance at 0.1 mg / kg / day for at least two weeks, the daily dose of the OCS, e.g., prednisone, may be further reduced by 2.5 mg every two weeks over one or more two-week periods, at the option of choice. In some embodiments, the daily dose of the OCS, e.g., prednisone, is maintained at 0.1 mg / kg / day for at least eight weeks, and then further reduced by 2.5 mg every two weeks over one or more two-week periods. In some embodiments, the daily dose of the OCS, e.g., prednisone, is reduced by 2.5 mg every two weeks over one or more two-week periods until the daily dose of the OCS, e.g., prednisone becomes zero (i.e., discontinuation of corticosteroid therapy). In some embodiments, each daily dose is optionally maintained for two weeks unless CIDP symptoms worsen.

[0405] Alternatively, after maintenance at 0.1 mg / kg / day for at least two weeks, the daily dose of the OCS, e.g., prednisone, may be further reduced by 1 mg per week over one or more one-week periods, at the option of choice. In some embodiments, the daily dose of the OCS, e.g., prednisone, is maintained at 0.1 mg / kg / day for at least eight weeks, and then further reduced by 1 mg per week over one or more one-week periods. In some embodiments, the daily dose of the OCS, e.g., prednisone, is reduced by 1 mg per week over one or more one-week periods until the daily dose of the OCS, e.g., prednisone becomes zero (i.e., discontinuation of corticosteroid therapy). In some embodiments, each daily dose is optionally maintained for one week unless CIDP symptoms worsen.

[0406] diagnosis In certain embodiments, the methods described herein may be used to assist in the diagnosis of CIDP. As described elsewhere herein, CIDP is a highly heterogeneous condition, difficult to diagnose, and prone to frequent misdiagnosis. The results presented herein demonstrate the efficacy of efgultigimod in the treatment of CIDP and establish CIDP as an autoimmune disease that responds to treatment with an FcRn antagonist. The methods described herein may be used to assist in the diagnosis of CIDP, based on the fact that a patient suspected of having CIDP (e.g., according to standard diagnostic criteria) and treated according to any of the embodiments described herein may be confirmed as positive for CIDP if they show a positive response to treatment. A positive response to treatment may be measured as control of disease activity, partial remission, or complete remission. A positive response to treatment may be measured as improvement or stabilization of symptoms, measured using any of the assessment methods described herein. In some embodiments, the methods described herein, where the FcRn antagonist is efgultigimod, are used to assist in the diagnosis of CIDP.

[0407] F. Pharmaceuticals This disclosure provides a pharmaceutical product containing efgultigimod and hyaluronidase approved for the treatment of CIDP. It also provides a method for treating CIDP, comprising administering the pharmaceutical product containing efgultigimod and hyaluronidase. Furthermore, it provides the use of the pharmaceutical product containing efgultigimod and hyaluronidase for the treatment of CIDP.

[0408] In some embodiments, the drug is optionally formulated for subcutaneous administration over a period of approximately 30 to 90 seconds. In some embodiments, the drug is administered in a total volume of approximately 5.6 mL. In some embodiments, the drug is administered in a total volume of 5.6 mL. In some embodiments, the drug is provided in a single-dose vial for subcutaneous administration via a winged infusion set.

[0409] In some embodiments, the pharmaceutical product is provided in a single-dose vial at a concentration of 180 mg efgultigimod / 2000 units of hyaluronidase per mL. In some embodiments, the pharmaceutical product is provided in a single-dose vial containing approximately 180 mg / mL of efgultigimod, approximately 2000 units / mL of recombinant human hyaluronidase (rHuPH20), approximately 1.4 mg / mL of L-histidine, approximately 2.2 mg / mL of L-histidine hydrochloride monohydrate, approximately 1.5 mg / mL of L-methionine, approximately 0.4 mg / mL of polysorbate 20, approximately 5.8 mg / mL of sodium chloride, and approximately 20.5 mg / mL of sucrose, at a pH of approximately 6.0.

[0410] In some embodiments, the pharmaceutical is provided in a single-dose vial containing 180 mg / mL of efgaltigimod, 2,000 U / mL of rHuPH20, 1.4 mg / mL of L-histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of L-methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, and 20.5 mg / mL of sucrose, at a pH of approximately 6.0.

[0411] In some embodiments, the pharmaceutical product is provided in a single-dose vial containing a 5.6 mL liquid formulation at pH 6.0, comprising 1008 mg of efgaltigimod, 11,200 units of rHuPH20, 7.8 mg of histidine, 12.3 mg of L-histidine hydrochloride monohydrate, 8.4 mg of methionine, 2.2 mg of polysorbate 20, 32.5 mg of sodium chloride, 114.8 mg of sucrose, and water for injection, USP.

[0412] In some embodiments, the pharmaceutical product is provided in a single-dose vial containing a 5.6 mL liquid formulation comprising 1,008 mg of efgaltigimod and 11,200 units of rHuPH20, where each mL of the vial solution has a pH of 6.0 and contains histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP.

[0413] In some embodiments, the pharmaceutical is provided in a single-dose vial containing 180 mg / mL of efgaltigimod, 2,000 units / mL of recombinant human hyaluronidase (rHuPH20), 1.4 mg / mL of histidine, 2.2 mg / mL of L-histidine hydrochloride monohydrate, 1.5 mg / mL of methionine, 0.4 mg / mL of polysorbate 20, 5.8 mg / mL of sodium chloride, 20.5 mg / mL of sucrose, and water for injection, USP, in a total volume of 5.6 mL at pH 6.0.

[0414] In some embodiments, the pharmaceutical product is the reference product.

[0415] In some embodiments, the drug is a reference described based on efgultigimod administered at a dose of 1000 mg. In some embodiments, the drug is a reference described based on efgultigimod administered at a dose of 1008 mg. In some embodiments, the drug is a reference described based on hyaluronidase administered at a dose of 11,200 units. In some embodiments, the drug is a reference described based on administration once a week or once every two weeks. In some embodiments, the drug is a reference described based on administration once a week. In some embodiments, the drug is a reference described based on administration once a week, followed by adjustment to administration once every two weeks based on clinical evaluation. In some embodiments, the drug is a reference described based on resumption of administration once a week in case of symptom exacerbation.

[0416] In some embodiments, the pharmaceuticals are enumerated references based on the first five injections and must be administered by or under the supervision of a healthcare professional, with subsequent treatments to be administered by a healthcare professional or may be administered at home by the patient or caregiver after appropriate training in subcutaneous injection techniques.

[0417] In some embodiments, the drug is approved for administration to adult patients. In some embodiments, the drug has an approved indication for the treatment of CIDP in adult patients with active disease despite treatment with corticosteroids or immunoglobulins.

[0418] In some embodiments, the drug induced an ECI response in 66.5% of a population of CIDP patients receiving 1008 mg / 11,200 units of efgaltigimod PH20 once weekly. In some embodiments, the median time to the first confirmed ECI in the CIDP patient population was 43 days from the first dose of the drug. In some embodiments, up to 40% of CIDP patients in the CIDP patient population had an ECI response within 4 weeks from the first dose of the drug. In some embodiments, 25% of CIDP patients in the CIDP patient population showed a clinically relevant improvement in at least one of the following: aINCAT score, I-RODS, or mean grip strength, within 9 days of the first dose of the drug. In some embodiments, the CIDP patient population consisted of 322 CIDP patients. In some embodiments, patients in the CIDP patient population who received the drug remained relapse-free for significantly longer than patients in the CIDP patient population who received placebo. In some embodiments, patients in the CIDP patient population who received the drug showed a 61% reduction in the risk of exacerbation compared to patients in the CIDP patient population who received placebo. In some embodiments, 69% of CIDP patients in the group receiving the medication showed evidence of improvement during two consecutive measurements after administration of the FcRn antagonist. In some embodiments, evidence of improvement is selected from an improvement of 1 or more points in aINCAT, an improvement of 4 or more points in I-RODS, or an improvement of 8 kPa or more in mean grip strength. In some embodiments, CIDP patients in the group receiving the medication experienced a longer time to clinical exacerbation compared to CIDP patients in the group receiving placebo. In some embodiments, clinical exacerbation is defined as an increase of 1 or more points in the aINCAT score. In some embodiments, clinical exacerbation is defined as an increase of 1 or more points in the aINCAT score during two consecutive measurements. In some embodiments, clinical exacerbation is defined as an increase of 2 or more points in the aINCAT score. In some embodiments, the longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant.

[0419] In some embodiments, the drug induces a hypersensitivity reaction selected from the group consisting of anaphylaxis and hypotension causing syncope. In some embodiments, the hypotension causing anaphylaxis or syncope occurs during or within one hour after administration of the drug. In some embodiments, the drug is contraindicated in patients with severe hypersensitivity to the fgultigimod alfa product, to hyaluronidase, or to any excipient of the drug.

[0420] In some embodiments, the drug induces an infusion-related reaction. In some embodiments, the infusion-related reaction is one or more of the following: hypertension, chills, shivering, chest pain, abdominal pain, and back pain. In some embodiments, if a mild to moderate infusion-related reaction occurs during administration of the drug, one or more subsequent doses of the drug are administered with close clinical observation, a slower infusion rate, and prior medication.

[0421] In some embodiments, the labeling of the drug includes a contraindication in patients with severe hypersensitivity to the fgultigimod alfa product, hyaluronidase, or any excipients in their formulations. In some embodiments, the labeling of the drug includes a warning for hypersensitivity reactions selected from anaphylaxis and hypotension causing syncope. In some embodiments, the labeling of the drug includes a warning for infusion-related reactions selected from hypertension, chills, shivering, chest pain, abdominal pain, and back pain. In some embodiments, the labeling of the drug indicates that appropriate treatment should be initiated if a severe infusion-related reaction occurs during administration of the product. In some embodiments, the labeling of the drug indicates that if a mild to moderate infusion-related reaction occurs during administration of the product, the patient may be re-challenged with close clinical observation, a slower infusion rate, and pre-medication.

[0422] In some embodiments, the drug induces anti-efgultigimod antibodies in 2% of subjects in a population of 117 CIDP patients after treatment with the drug. In some embodiments, the drug induces anti-efgultigimod antibodies in 6% of subjects in a population of 317 CIDP patients after treatment with the drug. In some embodiments, the drug induces neutralizing anti-efgultigimod antibodies in 0.3% of subjects in a population of 317 CIDP patients after treatment with the drug.

[0423] In some embodiments, the drug labeling includes data showing an ECI response in 66.5% of a population of CIDP patients who received 1008 mg / 11,200 units of efgaltigimod PH20 once weekly. In some embodiments, the drug labeling includes data showing that the median time to the first confirmed ECI in the CIDP patient population was 43 days from the first dose of the drug. In some embodiments, the drug labeling includes data showing that up to 40% of CIDP patients in the CIDP patient population had an ECI response within 4 weeks from the first dose of the drug. In some embodiments, the drug labeling includes data showing that 25% of CIDP patients in the CIDP patient population showed a clinically relevant improvement in at least one of the following: aINCAT score, I-RODS, or mean grip strength within 9 days of the first dose of the drug. In some embodiments, the CIDP patient population is 322 CIDP patients. In some embodiments, the drug labeling includes data showing that patients in the CIDP patient population who received the drug remained relapse-free for significantly longer than patients in the CIDP patient population who received placebo. In some embodiments, the labeling of the drug includes data showing that patients in a group of CIDP patients who received the drug showed a 61% reduction in the risk of exacerbation compared to patients in a group of CIDP patients who received placebo. In some embodiments, the labeling includes data showing improvement over two consecutive visits in 69% of a group of CIDP patients who received 1008 mg / 11,200 units of the drug once a week for up to 12 weeks. In some embodiments, improvement is an improvement of 1 or more points in aINCAT, an improvement of 4 or more points in I-RODS, or an improvement of 8 kPa or more in average grip strength. In some embodiments, the labeling includes data showing that CIDP patients who received the drug experienced a longer time to clinical exacerbation compared to CIDP patients who received placebo. In some embodiments, clinical exacerbation is an increase of 1 or more points in the aINCAT score. In some embodiments, clinical exacerbation is an increase of 1 or more points in the aINCAT score over two consecutive measurements. In some embodiments, clinical exacerbation is an increase of 2 or more points in the aINCAT score.In some embodiments, a longer time to clinical exacerbation is indicated by a hazard ratio of 0.394. In some embodiments, the longer time to clinical exacerbation is statistically significant. In some embodiments, the labeling indicates that patients who received the drug experienced a longer time to clinical exacerbation (i.e., an increase of 1 or more points in the aINCAT score) compared to patients who received placebo, as demonstrated by a hazard ratio of 0.394 [95% CI (0.253; 0.614) p < 0.0001], which is statistically significant. In some embodiments, the labeling of the drug includes any combination of features described above or elsewhere in this specification.

[0424] In some embodiments, prior to treatment with efgaltigimod PH20, the population of CIDP patients includes treatment-naïve patients, patients receiving immunoglobulins, and patients receiving corticosteroids.

[0425] In some embodiments, the CIDP patient population includes patients with CIDP that is unstable and refractory to treatment (CIDP Disease Activity Score (CDAS) 5B and 5C) prior to treatment with efgartigimod PH20, as well as patients with CIDP that is stable with existing treatments (CDAS 3 and 4) prior to treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having mild to severe impairment prior to treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having an INCAT score of 2 to 9 prior to treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having an IRODS of 11 to 61 prior to treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having an average grip strength of 1 to 120 kPa prior to treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having a mean INCAT score of 5 before treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having a mean IRODS of 37 before treatment with efgartigimod PH20. In some embodiments, the CIDP patient population is characterized by having a mean grip strength of 39 kPa before treatment with efgartigimod PH20.

[0426] Biosimilars and bioequivalents of the pharmaceutical products described herein are also included in this disclosure.

[0427] Furthermore, a method for treating CIDP is provided, comprising administering to a subject a pharmaceutical product containing efgultigimod and hyaluronidase, a biosimilar of a pharmaceutical product containing efgultigimod and hyaluronidase, or a bioequivalent of a pharmaceutical product containing efgultigimod and hyaluronidase. Also provided is the use of a pharmaceutical product containing efgultigimod and hyaluronidase, a biosimilar of a pharmaceutical product containing efgultigimod and hyaluronidase, or a bioequivalent of a pharmaceutical product containing efgultigimod and hyaluronidase for the treatment of CIDP in a subject.

[0428] In some embodiments, the drug, biosimilar, or bioequivalent is administered to the subject once a week or once every two weeks. In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously once a week. In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously once a week for at least four weeks. In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously once a week until the subject shows an ECI. In some embodiments, the drug, biosimilar, or bioequivalent is administered once a week until the subject shows an ECI during two consecutive measurements, optionally, two consecutive measurements taken approximately one week apart. In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously once a week until the subject shows an ECI twice over two weeks. In some embodiments, the ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, INCAT, or aINCAT score. In some embodiments, ECI is a clinical improvement in one or more of the following: I-RODS, mean grip strength, or INCAT score.

[0429] In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously once a week until the subject exhibits an ECMD. In some embodiments, ECMD is one or more of the following: an increase of 1 or more aINCAT score, a decrease of 4 or more I-RODS (using centile metrics), or a decrease of 8 kPa or more in average grip strength in one hand using a handheld dynamometer. In some embodiments, ECMD is an increase of 1 or more aINCAT score. In some embodiments, ECMD is an increase of 1 or more aINCAT score during two consecutive measurements, optionally, taken approximately one week apart. In some embodiments, ECMD is an increase of 1 or more aINCAT score during two consecutive measurements over two weeks. In some embodiments, ECMD is an increase of 2 or more aINCAT score.

[0430] In some embodiments, the drug, biosimilar, or bioequivalent is initially administered subcutaneously once a week, and then subcutaneously every two weeks based on clinical evaluation. In some embodiments, the clinical evaluation is performed by the healthcare provider. In some embodiments, the drug, biosimilar, or bioequivalent is initially administered subcutaneously once a week, and then subcutaneously every two weeks once an ECI (Endocrine Collision Indication) is demonstrated in the subject. In some embodiments, weekly subcutaneous administration of the drug, biosimilar, or bioequivalent is resumed in response to symptom exacerbation. In some embodiments, the drug, biosimilar, or bioequivalent is administered subcutaneously over approximately 30 to 90 seconds.

[0431] In some embodiments, the drug, biosimilar, or bioequivalent is initially administered by or under the supervision of a healthcare professional for at least five doses. In some embodiments, subsequent administrations of the drug, biosimilar, or bioequivalent are performed by a healthcare professional or by the patient or caregiver.

[0432] In some embodiments, the subjects have an active disease despite treatment with corticosteroids or immunoglobulins.

[0433] In some embodiments, the methods or uses described herein further include monitoring the subject for hypersensitivity reactions selected from the group consisting of anaphylaxis and hypotension causing syncope, and initiating appropriate measures to mitigate the hypersensitivity reaction when detected.

[0434] In some embodiments, the methods or uses described herein further include monitoring the subject for infusion-related reactions and initiating appropriate measures when a severe infusion-related reaction is detected. In some embodiments, the infusion-related reaction includes one or more of the following: hypertension, chills, shivering, chest pain, abdominal pain, and back pain.

[0435] In some embodiments, the subject is, for example, a human being, such as an adult. [Examples]

[0436] The present invention will be further understood by reference to the following non-limiting embodiments.

[0437] Example 1: Phase 2 study to investigate the efficacy, safety, and tolerability of efgaltigimod PH20SC in adult patients with CIDP. 1.1 Protocol Summary 1.1.1 Rationale of Clinical Trials There is an unmet medical need for an effective treatment of CIDP that offers a better safety and tolerability profile than current treatments, as well as easier administration. A weekly subcutaneous (SC) treatment option consisting of efgaltigimod PH20SC, administered within minutes, may offer clinically significant benefits to CIDP patients.

[0438] In the ADHERE clinical trial described herein (protocol number: ARGX-113-1802), patients with CIDP were administered 1000 mg of efgaltigimod PH20SC. This dose was well tolerated in a previous Phase 1 trial ARGX-113-1901 in healthy adults and reduced immunoglobulin G (IgG) levels to levels associated with clinical benefit in previous trials in patients with autoimmune diseases (i.e., patients with systemic myasthenia gravis [gMG] and patients with primary immune thrombocytopenia [ITP]).

[0439] 1.1.2 Clinical Trial Methodology The ADHERE clinical trial was a phase 2 prospective, multicenter study investigating the efficacy, safety, tolerability, immunogenicity, pharmacokinetics, and disease progression of fgultigimod PH20SC administered via SC in patients aged 18 years or older with CIDP. The trial was conducted in two stages: an open-label stage A and a randomized, dropout, double-blind, placebo-controlled stage B. The complete schema is shown in Figure 1.

[0440] During a maximum 28-day screening period, the diagnosis of CIDP was confirmed by the CIDP Confirmation Committee (CCC), and overall eligibility was confirmed by medical monitors. Eligible patients receiving treatment for CIDP at the time of screening discontinued their treatment and entered a run-in period of up to 12 weeks until ECMD was confirmed (i.e., observed during trial visits), at which point eligible patients entered Stage A at baseline (D1A).

[0441] Eligible patients who were treatment-naive or had discontinued treatment with corticosteroids and / or intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) at least six months prior to screening (and were considered equivalent to treatment-naive patients) entered Stage A directly during screening if, during the three months prior to screening, further documented evidence of worsening of the total aINCAT impairment score, referred to as the “aINCAT score,” was available compared to a previous aINCAT score within six months prior to screening.

[0442] Patients eligible for Stage A received the open-label investigational drug (IMP) as weekly SC doses of fgultigimod PH20SC for a maximum of 12 weeks (with an optional additional week to confirm endocrine infection if necessary), for at least four doses. Patients were monitored for endocrine infection throughout Stage A.

[0443] Patients who met the criteria for ECI (Endocrine Corruption) during two consecutive visits (confirmed ECI status) were rolled over to randomized withdrawal placebo-controlled Stage B. Patients who did not confirm ECI were not eligible for Stage B and were terminated after a safety follow-up visit 28 days after the last dose of IMP.

[0444] After the first 30 patients reached the end of Stage A, an interim analysis was conducted on the proportion of patients with confirmed ECI using the exact (Clopper-Pearson) 90% one-sided lower limit confidence interval (CI) for deciding whether to continue the trial (go / no-go). During the interim analysis, the trial continued without interruption for trial enrollment or for visits or treatment of patients who had participated in any trial period.

[0445] Patients with confirmed ECI in Stage A entered a double-blind, randomized withdrawal Stage B, where they were randomized in a 1:1 ratio at Stage B baseline (D1B) to receive weekly IMP consisting of either efgaltigimod PH20SC or placebo. Randomized withdrawal Stage B lasted up to 48 weeks.

[0446] All patients randomized to the double-blind, randomized withdrawal stage B received weekly IMP administrations but were returned to the clinic every four weeks. Randomized IMP treatment was administered only after completion of all indicated evaluations. Patients were discharged from the center if there were no safety concerns in the opinion of the principal investigator. During the stage B trial visits, patients were given the option of coming to the trial center weekly for drug administration or receiving home nursing services for IMP injections. The most suitable solution was provided based on agreement between the principal investigator, facility staff, and the patient. IMP administrations were always made within a ±2 day time window with respect to the pre-planned administration day.

[0447] Patients who completed week 48 and, in the investigator's view, benefited from the study treatment at week 48, or who experienced a deterioration of 1 point in their aINCAT score or 2 or more points in their aINCAT score compared to stage B baseline (confirmation was not required for the latter), were permitted to roll over to an open-label extension (OLE) study while receiving IMP. Patients who completed week 48 but did not roll over to the OLE study, and those who discontinued early, visited for safety follow-up 28 days after their last IMP dose, discontinued the study, and received treatment deemed appropriate by the investigator.

[0448] The trial was stopped when 88 events were observed in the primary endpoint analysis for Stage B. Patients in Stage A and Stage B made an early discontinuation visit, and patients receiving IMP were given the opportunity to continue efgaltigimod PH20SC treatment in the OLE trial. In addition, at the time of the 88th event, run-in patients were also given the option to roll over to the OLE trial after making an early discontinuation visit. Patients who did not roll over to the OLE trial attended a follow-up visit 28 days after their last IMP dose.

[0449] From Stage A onward, patients received training for self-administration of IMP as predicted in the OLE trial (not the ARGX-113-1802 trial). 1.1.3 Purpose 1.1.3.1 Stage A (Open-label, Efgalchigimod PH20SC; 4-12 weeks [optional +1 additional week]) Main purpose • Evaluate the activity of efgultigimod PH20SC (efgultigimod co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]) based on the proportion of patients classified as treatment responders. Secondary purpose • Evaluate the time to clinical improvement. • Determine the therapeutic effect of efgaltigimod PH20SC based on clinical functional assessments of motor function and muscle strength. • To evaluate the short-term safety and tolerability of Efgalchigimod PH20SC. • Evaluate the pharmacokinetics (PK) of efgaltigimod PH20SC. • To evaluate the pharmacodynamic (PD) effects of efgaltigimod PH20SC. • Evaluate the immunogenicity of efgaltigimod and rHuPH20. • To evaluate the EuroQol 5-dimensional and 5-level health-related quality of life questionnaire (EQ-5D-5L). exploratory purpose • Evaluate outcomes (PROs) reported by additional patients (including quality of life and satisfaction with treatment reported by additional patients). • To evaluate biomarkers for CIDP disease activity. • To evaluate the relationship between biomarkers and clinical outcomes. • Explore validation analysis of multiple evaluation criteria. 1.1.3.2 Stage B (Double-blind, randomized withdrawal, efgaltigimod PH20SC or placebo, up to 48 weeks) Main purpose • Determine the efficacy of efgaltigimod PH20SC compared to placebo based on the time required for the first evidence of clinical exacerbation to occur. Secondary purpose • To determine the efficacy of efgaltigimod PH20SC compared to placebo, based on clinical functional assessments of disease impairment, motor function, and muscle strength. • Evaluate the safety and tolerability of Evgalchigimod PH20SC. • Evaluate the pharmacokinetics of Evgalchigimod PH20SC. • To evaluate the PD effect of Efgalchigimod PH20SC. • Evaluate the immunogenicity of efgaltigimod and rHuPH20. • Evaluate the EQ-5D-5L. exploratory purpose • Evaluate additional PROs (including additional patient-reported quality of life and satisfaction with treatment). • To evaluate biomarkers for CIDP disease activity. • To evaluate the relationship between biomarkers and clinical outcomes. • Explore validation analysis of multiple evaluation criteria.

[0450] 1.1.4 Maximum duration of patient involvement in the trial After a screening period of up to 28 days and a run-in period of up to 12 weeks, the total duration of IMP treatment was up to 61 weeks and included two treatment stages. Stage A is an open-label treatment of efgaltigimod PH20SC for up to 12 weeks (with the option of an additional week). Stage B involved double-blind treatment with IMP (efgartigimod PH20SC or placebo) for up to 48 weeks.

[0451] For patients who did not roll over to the extension study or who discontinued IMP early, the follow-up period was 28 days after the last dose of IMP.

[0452] The longest total trial period was 80 weeks, while the longest IMP trial period was 61 weeks. • Screening period: up to 28 days • Run-in period: Up to 12 weeks (not required for patients with no prior treatment experience) Stage A: 4-12 weeks (an additional week can be added at will) Stage B: Up to 48 weeks • Follow-up period: 28 days after the last dose of IMP for patients who were not enrolled in the OLE trial ARGX-113-1902.

[0453] 1.1.5 Evaluation Items 1.1.5.1 Population for Analysis Safety population: The safety population for Stage A (SAF-A) included all patients who received at least one dose of IMP in Stage A. The safety population for Stage B (SAF-B) included all patients who received at least one dose of IMP in Stage B.

[0454] Modified Intention to Treat (mITT) population: The mITT population included all randomized patients who received at least one dose of IMP at stage B.

[0455] Protocol (PP) population: The PP population included all stage B patients in the mITT population for which no significant protocol deviations were reported. 1.1.5.2 Stage A Primary evaluation criteria: • Percentage of patients with confirmed ECI. Secondary evaluation criteria: • Evidence of clinical activity: - The time until the first confirmed ECI. - Changes over time from Stage A baseline (D1A): ○ aINCAT score ○MRC Total Score ○ 24-item I-RODS disability score ○TUG score ○Average grip strength as measured by a Martin dynamometer. ·Safety: - Exposure-adjusted incidence rates of therapeutic adverse events (TEAEs) and serious adverse events (SAEs) occurring during treatment, based on organ-specific classification (SOC) and preferred terminology (PT); • The incidence rate of clinically significant test abnormalities. • PK Profile: - Time course of efgaltigimod serum concentration prior to administration during Stage A. • PD Profile: - Changes in serum IgG levels (total IgG) over time during Stage A. ·Immunogenicity: - Percentage of patients in Stage A with conjugated antibodies (BAb) to efgaltigimod and / or rHuPH20, and the titer of these conjugated antibodies (BAb). - Presence of neutralizing antibodies (NAb) against efgartigimod during Stage A and the titer of NAb against rHuPH20. • PRO: - Changes in EQ-5D-5L over time from D1A during Stage A. Exploratory evaluation criteria: Outcomes reported by additional patients • Changes over time from the Stage A baseline (D1A) during Stage A: - Short Form Pain Indicator (BPI-SF) - (9 items) Treatment satisfaction questionnaire regarding medication (TSQM-9) -Rush Conversion- Fatigue Severity Scale (RT-FSS) - Hospital Anxiety and Depression Scale (HADS) - Changes in overall patient impression (PGIC) Biomarker analysis • Changes over time from Stage A baseline (D1A) in autoantibody levels, including but not limited to anti-GM1, anti-LM-1, anti-NF-155, anti-CNTN1, anti-Caspr-1 antibody levels, and anti-myelinated nerve antibody levels. 1.1.5.3 Stage B Primary evaluation criteria: • Time to the first aINCAT exacerbation compared to Stage B baseline. Note: The time to the first aINCAT exacerbation was defined as the time from the initial dose of double-blind IMP to the first increase of 1 point in the aINCAT score compared to the Stage B baseline, provided that the exacerbation was confirmed at a follow-up visit 3 to 7 days after the initial 1-point increase in the aINCAT score. Confirmation was not required for patients whose aINCAT score increased by 2 points or more compared to the Stage B baseline. Secondary evaluation criteria: • Clinical efficacy: - Time until CIDP disease progression. Note: Time to CIDP disease progression is defined as the time from the first dose of double-blind IMP until the first I-RODS score, using the centile metric, decreases by 4 points or more compared to the baseline at stage B. - Percentage of patients with an improved level of function compared to Stage B baseline, as measured by the increase in the 24-item I-RODS score up to 48 weeks. - Changes from baseline in Stage B over time: ○ aINCAT score ○MRC Total Score ○ 24-item I-RODS disability score ○TUG score ○Average grip strength as measured by a Martin dynamometer. - The time it takes for the 24 I-RODS items in Stage B to decrease by 10%. ·Safety: - The appearance rate of TEAE and SAE by SOC and PT during Stage B. - The prevalence of clinically significant laboratory abnormalities during Stage B. • PK Profile: - Time course of efgaltigimod serum concentration prior to administration during Stage B. • PD Profile: - Changes in serum IgG levels (total IgG) over time during Stage B. ·Immunogenicity: - Percentage of patients in Stage B with BAb for efgaltigimod and / or rHuPH20 and BAb titer. - Presence of NAb against evgarchigimodo and the titer of NAb against rHuPH20 during stage B. • PRO: - Changes in EQ-5D-5L over time from the baseline in Stage B during Stage B. Exploratory evaluation criteria: Outcomes reported by additional patients • Changes from the baseline of Stage B over time: - Short Form Pain Indicator (BPI-SF) - (9 items) Treatment satisfaction questionnaire regarding medication (TSQM-9) -Rush Conversion- Fatigue Severity Scale (RT-FSS) - Hospital Anxiety and Depression Scale (HADS) - Changes in overall patient impression (PGIC) Biomarker analysis • Changes in autoantibody levels over time from baseline in Stage B during Stage B, including but not limited to anti-GM1, anti-LM-1, anti-NF-155, anti-CNTN1, anti-Caspr-1 antibody levels, and anti-myelinated nerve antibodies.

[0456] 1.2 Test Design 1.2.1 Overall Design The ADHERE trial was a phase 2 prospective, multicenter study to investigate the efficacy, safety, tolerability, pharmacokinetics (PK), and disease progression (PD) of efgaltigimod PH20SC in patients aged 18 years or older with CIDP. The trial was conducted in two stages: an open-label stage A and a randomized withdrawal stage B.

[0457] Following a screening period for all patients and a run-in period for eligible patients (those not previously treated), all patients entered open-label Stage A at baseline (D1A) and received the study treatment (efgaltigimod PH20SC) once a week for up to 12 weeks (with an optional additional week). During this period, patients with confirmed ECI (Emergency Infection) at two consecutive visits were moved to randomized withdrawal placebo-controlled Stage B, where they were randomized at Stage B baseline (D1B) in a 1:1 ratio to either efgaltigimod PH20SC or placebo. Randomized withdrawal Stage B lasted up to 48 weeks.

[0458] The exam included the following period: • Screening period: up to 28 days, • Run-in period: up to 12 weeks (excluding patients with no prior treatment experience) • Stage A: Open-label treatment with fgultigimod PH20SC for up to 12 weeks (with the option of an additional week) (weekly trial visits). • Stage B: Double-blind, randomized withdrawal therapy with efgaltigimod PH20SC or placebo for up to 48 weeks (trial visits once every 4 weeks), and • Follow-up: 28 days after the last dose of IMP if the patient did not intend to roll over to the open-label extension (OLE) trial ARGX-113-1902.

[0459] The total trial period for each patient was a maximum of 80 weeks, with the maximum IMP being 61 weeks. The trial schema is provided in Figure 1.

[0460] 1.2.1.1 Screening Period During a screening period of up to 28 days, the CIDP Confirmation Committee (CCC) reviewed the principal investigator's diagnosis of CIDP, and overall eligibility was confirmed by a medical supervisor. To participate in the study, participants had to be diagnosed with CIDP as confirmed by the CCC and medical supervisor.

[0461] The Clinical Clinical Committee (CCC) consisted of neurologists with at least 10 years of experience in diagnosing CIDP and documented records of at least 100 CIDP diagnoses. The CCC ensured that the CIDP trial population included in this study met the official EFNS / PNS 2010 diagnostic criteria (Van den Bergh et al., 2010). These were used to define possible or definitive progressive or recurrent forms of CIDP in which both sensory symptoms and limited motor function, or limited motor function alone, had to be present for a patient to qualify for the trial.

[0462] 1.2.1.2 Run-in period Following the screening period, and depending on the type of prior treatment permitted for CIDP, eligible patients initiated a run-in period. The run-in period lasted up to 12 weeks. Depending on the patient's prior or current treatment at the time of screening, the run-in period included: 1. Patients who had received no prior treatment for CIDP were permitted to skip the run-in period if there was documented evidence of deterioration in their aINCAT score within 3 months prior to screening, compared to their previous aINCAT score within 6 months prior to screening. (Patients who had not been treated with monthly or daily pulse corticosteroids, IVIg, or SCIg for at least six months prior to screening were considered equivalent to treatment-naive patients.) 2. Patients treated with IVIg or SCIg during screening discontinued IVIg or SCIg treatment at the start of the run-in period (i.e., RI-V1). 3. Patients who were being treated with pulsed corticosteroids (IV or oral) or daily oral corticosteroids of 10 mg or less during screening discontinued corticosteroid treatment at the start of the run-in period (i.e., RI-V1).

[0463] Patients were monitored by collecting grip strength, I-RODS score, MRC total scoring, aINCAT score, and TUG test data. Regular scheduled visits to the study site were planned every four weeks.

[0464] Patients received appropriate training and instructions to assess their disability status weekly using I-RODS and grip strength. Patient I-RODS scores and average grip strength were captured, calculated, and transmitted to an electronic case report form (eCRF). If a patient observed any of the following exacerbation signals, a trial visit was arranged within 5 working days for physician evaluation. • I-RODS exacerbation of 4 points or more (using the centile metric), and / or • Average grip strength worsened by more than 8kPa with one hand using a handheld dynamometer.

[0465] In the study, the diagnosing physicians evaluated whether exacerbations could be confirmed by meeting the criteria for ECMD.

[0466] Any patient demonstrating ECMD at the testing site was immediately admitted to Stage A. If a patient did not provide evidence of ECMD by the end of the run-in period, they were recorded as a run-in failure.

[0467] 1.2.1.3 Stage A All patients with ECMD initiated Stage A with an initial dose of open-label IMP at Stage A baseline (D1A). After completing all pretreatment baseline assessments, patients received weekly SC infusions of IMP consisting of fgaltigimod PH20SC for up to 12 weeks (with an optional additional week), and received at least four SC injections of IMP.

[0468] Procedures completed during D1A and other trial visits are provided in the Activity Schedule (SoA) in Table 9. Each patient remained in Stage A and returned to the trial site weekly, as documented in the SoA, until an ECI for D1A was identified by the evaluating investigator during two consecutive visits.

[0469] The interim analysis of the results was conducted after the first 30 patients in Stage A had reached the end of Stage A (EOSA). The trial continued uninterrupted throughout the interim analysis, neither for trial enrollment nor for patient visits or treatments during any trial period.

[0470] Patients who did not show an ECI during two consecutive visits in Stage A were classified as non-responders. Non-responders terminated the study and had a follow-up visit 28 days after the last dose of IMP, after which they received treatment deemed appropriate at the discretion of the principal investigator.

[0471] All patients with confirmed ECI were randomized to one of two treatment groups (efgartigimod PH20SC or placebo SC) to initiate Stage B. Randomization was performed on the same day as ECI confirmation. Patients who showed ECI only at their last visit in Stage A (i.e., one week after A-V12) were permitted to extend Stage A for another week with one additional consecutive visit. If ECI was observed for the first time at this visit, the patient was then scheduled for a consecutive visit one week later. The reason for this possible extension of Stage A for one week was to confirm ECI at the consecutive visit one week later (and, if ECI was confirmed, to randomize the patient in Stage B). If ECI was not confirmed after the additional one week in Stage A, the patient was scheduled for an EOSA visit and the trial was terminated (after a follow-up visit 28 days after the last IMP dose).

[0472] During Stage A, IMP was administered in-house after blood samples were taken for laboratory safety, PK, PD, immunogenicity, and / or biomarker analysis, as well as after all assessments necessary for determining ECI. During Stage A, all patients were trained for self-administration of IMP (as predicted by the OLE test). [Table 9] TIFF2026524664000011.tif247170TIFF2026524664000012.tif240170TIFF2026524664000013.tif248170

[0473] 1.2.1.4 Stage B At screening, during the run-in period (from visit RI-V1 to visit RI-V4), and at baseline in Stage A (D1A; visit A-V1) before the first treatment in Stage A, as well as the treatment response during Stage A, each patient's eligibility for randomization in Stage B at baseline (D1B) was determined.

[0474] Patients with ECI in Stage A were randomized in a 1:1 ratio at Stage B baseline (D1B) to receive weekly doses of either efgaltigimod PH20SC or placebo.

[0475] All patients randomized to a double-blind, randomized withdrawal stage B received weekly IMP administration but were returned to the clinic at 4-week intervals. At each of these visits, specific procedures as specified in the activity schedule (SoA) in Table 10 were performed.

[0476] Patients were discharged from the study center after all procedures planned for their visit in accordance with the State of Action (SoA) had been performed and, in the opinion of the principal investigator, no safety concerns existed.

[0477] This trial was terminated when 88 events were observed for the primary endpoint analysis of Stage B. At this point, patients in Stage A and Stage B underwent an early discontinuation visit, and patients receiving IMP were given the opportunity to continue efgaltigimod PH20SC treatment in the OLE trial (in this case, the early discontinuation visit in the ARGX-113-1802 trial may coincide with the rollover visit). Patients who did not roll over to the OLE trial attended a follow-up visit 28 (±3) days after their last IMP dose.

[0478] In the OLE trial (ARGX-113-1902), patients were given the opportunity to continue treatment with efgaltigimod PH20SC if any of the following three conditions occurred. 1. The patient experienced clinical exacerbation (i.e., worsening of the aINCAT score) during Stage B. 2. The patient completed the 48-week visit for stage B without clinical exacerbation. 3. The 88th event in Stage B was recorded, and the patient had received IMP in either Stage A or Stage B.

[0479] The event is a deterioration in the aINCAT score in any of the patients treated during Stage B.

[0480] In addition, at the 88th event, run-in patients were given the option to roll over to the OLE trial after visiting for early discontinuation.

[0481] During Stage B, patients received further training for self-administration of IMP (predicted in the OLE trial, not the ARGX-113-1802 trial), as specified in the SoA in Table 10. Patients who experienced clinical exacerbations or who completed their 48-week visit were also eligible to enter the safety follow-up period and complete the trial without rolling over to the OLE trial.

[0482] 1.2.1.5 Follow-up A follow-up visit was performed 28 days after the last dose of IMP (in case of IMP or early termination of the trial), or if the patient did not meet the criteria for Stage A ECI (non-responder), or if the patient did not roll over to the OLE trial ARGX-113-1902, or 28 days after the last dose of Stage B. [Table 10] TIFF2026524664000015.tif248170TIFF2026524664000016.tif247170

[0483] 1.2.2 Scientific basis for test design The ADHERE trial design incorporated several key elements from the PATH trial (van Schaik et al., 2018). The treatment duration (stage A) was available to all patients who demonstrated evidence of disease activity during the run-in period.

[0484] The run-in period had two objectives. • Select patients with evidence of clinical disease activity (enriched design) Both ensure that the half-life of the previous drug (if applicable) has elapsed and that the clinical effect does not impair the efficacy analysis of the trial.

[0485] The pre-randomization observation period for treatment (Stage A) could be any length of 4 to 13 weeks. The post-withdrawal observation period in this trial (i.e., for patients in the placebo group during Stage B) was up to 48 weeks. Careful attention was paid to the procedures for monitoring patients and evaluating trial endpoints to ensure that patients failing the assigned treatment were rapidly identified.

[0486] The advantage of this trial design was that individuals who received the experimental intervention continued to do so only if they responded, whereas those who received the placebo only did so until their symptoms relapsed. A further advantage of this design was the ability to study long-term efficacy or safety (withdrawal effects).

[0487] The trial design allowed for the collection of information regarding the occurrence of therapeutic effects and whether the effects persisted after withdrawal from the medication or whether a rebound phenomenon occurred (placebo group). Furthermore, the trial also generated placebo response data in such populations, which are intended for further clinical development.

[0488] Any difference observed between the group receiving continuous treatment and the group randomized to placebo at stage B demonstrates the effectiveness of aggressive treatment.

[0489] All eligible patients initiated participation in the trial throughout the open-label period (Stage A), and all patients received active treatment. This selection was deemed necessary to provide minimal treatment with efgaltigimod PH20SC to all patients with active disease, even those who would be randomized to the placebo group after this period (in Stage B). Stage A had a variable duration of at least 4 weeks and up to 12 weeks (with an optional additional week), during which patients were treated with weekly SC doses until clinical improvement was achieved, maintained over two consecutive visits. This variable duration was chosen to achieve the greatest IgG reduction to maximize the duration of the effect. The maximum number of injections was set at 12 (or 13 in the case of the optional additional week), in line with the clinical practice of other treatments (3 months).

[0490] As an introduction to the placebo group, an initial open-label treatment (Stage A) with efgaltigimod PH20SC was planned for all patients. This allowed patients to receive active treatment before potential randomization to placebo (during Stage B), making the design more acceptable within the current context of highly effective treatment criteria for this debilitating disease. In addition, Stage A, followed by randomization to the placebo group, made it possible to establish how long the treatment effect lasted before clinical evidence of disease activity reappeared. In this way, the trial allowed for evaluation through biomarker analysis whether an individualized treatment schedule could be an option in clinical practice.

[0491] Patients experiencing clinical exacerbations were offered the opportunity to roll over to another OLE trial receiving weekly doses of efgultigimod PH20SC, as measured by an increase in their aINCAT score at any point during Stage B. Double-blinding of the original treatment allocation was maintained throughout the trial, even at the time of withdrawal.

[0492] The possibility of rolling over to the OLE trial made this trial attractive to patients who knew that effective open-label treatment would be available again (in the OLE trial), despite the option of benefiting from open-label treatment during Stage A and being randomized to placebo, and who knew they might potentially worsen in Stage B of the randomized trial.

[0493] All efficacy, safety, and quality of life assessments used in this study were standard, i.e., widely used, reliable, accurate, and relevant (including the CIDP study).

[0494] The biomarker analysis was exploratory, and biomarkers were selected to evaluate the therapeutic effect of efgultigimod PH20SC on the physiological pathology of CIDP and to assess the correlation between biomarkers and clinical outcomes. Evaluation of these biomarkers could enable the development of personalized therapeutic approaches with efgultigimod PH20SC that have prognostic values ​​for the likelihood of clinical exacerbation or predictive values ​​for establishing the likelihood of a treatment response. However, these are not currently listed as acceptable surrogate biomarkers. For this reason, this evaluation was exploratory in nature. Total human IgG levels themselves are merely a measure of how long the decline in IgG levels persists after discontinuation of treatment with efgultigimod PH20SC. This was a relevant reference marker for these patients who were randomized to the placebo group after the induction period.

[0495] 1.2.3 Logical basis for dosage A dose of 1000 mg of efgaltigimod PH20SC was selected for both Stage A and Stage B. Based on population PK / PD modeling, this dose of efgaltigimod PH20SC (administered once weekly) was predicted to be comparable to 10 mg / kg of efgaltigimod administered once weekly as an IV infusion in terms of its effect on IgG levels. IV dose of efgaltigimod 10 mg / kg: 1. Transient clinical efficacy was demonstrated in a Phase 2 trial in ITP patients, and long-term clinical efficacy was demonstrated in a Phase 2 trial in MG patients after four weekly intravenous administrations. 2. It was shown to produce results similar to the saturated PD effect. Dosing medication more frequently than once a week is not expected to result in improved PD effects (i.e., further reduction of autoantibodies) and / or clinical benefits, and may be associated with a lower optimal risk / benefit ratio. Lower dosages are expected to result in lower PD effects and may therefore lead to inconsistent and / or incomplete clinical responses, which is undesirable given the severe and chronic symptoms of CIDP. Therefore, once-weekly dosing is preferred until the patient is in a stable clinical state. 3. A favorable safety profile was demonstrated in a Phase 2 trial in patients with MG and ITP.

[0496] In addition, based on favorable Phase 3 results in patients with MG, efgaltigimod IV at a dose of 10 mg / kg is approved in the United States (US) and the EU (in both regions for AChR-Ab seropositive patients), as well as in Japan (for patients who do not respond adequately to steroid or nonsteroidal immunosuppressive therapy).

[0497] Studies in healthy participants showed that the pattern of total IgG level decline over time after four weekly injections of efgartigimod PH20SC 1000 mg was comparable to the pattern observed after four weekly injections of efgartigimod IV at 10 mg / kg.

[0498] rHuPH20 is approved in the United States as Hylenex. Co-formulations of rHuPH20 with other active ingredients are approved in the United States and the EU (e.g., HERCEPTIN HYLECTA / Herceptin SC, RITUXAN HYCELA / MabThera SC, HYQVIA / HyQvia, respectively) at a rHuPH20 concentration of 2000 U / mL for SC injection volumes ranging from 5 to 13.4 mL.

[0499] 1.2.4 Rationale for Randomization and Blinding Stage A was open-label with administration of efgaltigimod PH20SC. In Stage B, patients were randomized in a 1:1 ratio to either double-blind efgaltigimod PH20SC or placebo. Patients were stratified according to prior CIDP drug therapy and the decrease in aINCAT score during Stage A. 1: Previous CIDP drug therapy: • No prior treatment experience, • Pulse corticosteroid therapy or oral corticosteroids equivalent to prednisolone / prednisone ≤10 mg / day IVIg or SCIg treatment. 2: aINCAT score: • No change in aINCAT score during Stage A. • The aINCAT score decreases by 1 or more points during Stage A.

[0500] Except for deblinding for safety reasons, Stage B remained double-blinded for treatment assignments throughout the entire randomization withdrawal period, even if a patient withdrew from the trial or entered the OLE trial ARGX-113-1902. The treatment each patient received was not disclosed to the principal investigator, research site staff, patients, the sponsor, or the sponsor's designated contract research organization (CRO).

[0501] 1.2.5 Rollover to Open-Label Extension (OLE) Trials Patients receiving IMP who, in the opinion of the investigator, benefited from the study treatment at week 48, or who experienced clinical exacerbation (i.e., worsening of aINCAT score) during Stage B of treatment, will be offered the option to roll over to a long-term single-arm OLE trial, during which patients will be treated once weekly with SC-efgartigimod PH20SC. The dose and frequency used in OLE will be the same as those given to patients enrolled in Stage A of this trial.

[0502] Patients who were receiving IMP at stage A or stage B, or who were run-in at the moment of recording the 88th event in the trial, were offered the option to make an early discontinuation visit and roll over to the OLE trial because the ARGX-113-1802 trial was stopped at that moment. The event was a deterioration in the aINCAT score in any of the patients treated during stage B.

[0503] 1.3 Test Group Prior to each trial-related evaluation, each patient signed an Informed Consent Form (ICF). Before giving informed consent, patients were instructed not to participate in any other clinical trials involving medical intervention or data collection until the current trial was completed.

[0504] Patients were classified as eligible if they met all inclusion criteria, did not meet any exclusion criteria, and had an eligible CIDP diagnosis confirmed by the CCC and a medical monitor.

[0505] 1.3.1 Inclusion Criteria Patients were eligible to be included in the study only if all of the following criteria were met. 1. The ability to understand the requirements of the study and to demonstrate the willingness and ability to comply with written informed consent (including consent regarding the use and disclosure of research-related health information) and the study protocol procedures (including required visits to the study). 2. Male or female patients who are 18 years of age or older at the time they sign the informed consent form. 3. Diagnosed with progressive or recurrent CIDP, possibly or confirmed, according to the criteria of the European Federation of Neurological Societies / Peripheral Nerve Society (EFNS / PNS, 2010). 4. CIDP disease activity status (CDAS) score ≥ 2 at screening (Gorson et al., 2019). 5. INCAT score ≥ 2 at the first run-in visit (RI-V1; for patients entering run-in) or at Stage A baseline (A-V1; for treatment-naive patients with documented evidence of worsening of total aINCAT disability score within 3 months prior to screening). Patients with an INCAT score of 2 at trial participation were required to have this score exclusively from the lower limb disability score, and for patients with an INCAT score of 3 or higher at trial participation, there were no specific requirements regarding the arm or lower limb score. 6. One of the following treatment conditions must be met: • Currently (i.e., within the past 6 months), the patient is being treated with pulse corticosteroids, oral corticosteroids equivalent to prednisolone / prednisone ≤ 10 mg / day, and / or IVIg or SCIg, and the patient expressed an intention to discontinue this treatment at the first run-in visit (RI-V1), or • No prior treatment (no prior treatment experience), or Treatment with corticosteroids and / or IVIg or SCIg was discontinued at least 6 months prior to screening. Note: Patients who had not been treated with monthly or daily corticosteroids, IVIg, or SCIg for at least six months prior to screening were considered equivalent to treatment-naive patients. 7. Potentially pregnant women who have a negative pregnancy test at screening and whose urine pregnancy tests remain negative up to Stage A baseline (D1A). Women of childbearing potential were required to use an acceptable method of contraception from the time of signing the ICF until the last dose of IMP.

[0506] 1.3.2 Exclusion criteria Patients were excluded from the study if they met any of the following criteria: 1. Purely sensory atypical CIDP (EFNS / PNS definition). 2. Other causes of polyneuritis, including: - Multifocal motor neuritis - Monoclonal immunoglobulinemia of unknown significance due to anti-myelin-associated glycoprotein immunoglobulin M (IgM) antibodies - Hereditary demyelinating neuritis POEMS syndrome presents with polyneuropathy, organomegaly, endocrine disorders, M-proteinemia, and skin changes. - Lumbosacral nerve root plexus disorder - Polyneuritis most likely caused by diabetes -Polyneuritis most likely to be caused by a systemic disease. - Drug or toxin-induced polyneuritis. 3. Any other disease that can better explain the patient's signs and symptoms. 4. Any history of myelopathy or evidence of central demyelination. 5. Current or past history of alcohol, drug, or pharmacotherapy abuse (within 12 months of screening). 6. Severe mental disorders (such as severe depression, psychosis, or bipolar disorder), a history of suicide attempts, or current suicidal ideation that, in the opinion of the principal investigator, could pose an excessive risk to the patient or could affect adherence to the study protocol. 7. Patients with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infections at the time of screening, including patients with active viral infections at the time of screening that are positive for the test: • Active hepatitis B virus (HBV): Serological panel test results indicating active (acute or chronic) infection. • Active hepatitis C virus (HCV): Serologically positive for HCV-Ab, Human immunodeficiency virus (HIV) positive serology associated with a condition defining acquired immunodeficiency syndrome (AIDS) or clusters of differentiated 4 (CD4) counts of 200 cells / mm3 or less. 8. Total IgG level less than 6 g / L at the time of screening. 9.a. Treatment in the following cases: • Within 3 months prior to screening (the longer of 5 times the drug's half-life): plasma exchange or immunoadsorption, all combination Fc-containing therapies or other biological agents, or any other investigational product. • Within 6 months prior to screening: Rituximab, alemtuzumab, any other monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, any other immunomodulatory or immunosuppressive agent, and oral corticosteroids greater than 10 mg / day. This may include patients using IVIg, SCIg, pulse corticosteroids, and oral daily corticosteroids of 10 mg / day or less. • Patients who use (or intend to use) prohibited drugs and therapies during the trial. 10.a. Pregnant and breastfeeding women, as well as women planning to become pregnant during the trial. 11. In the opinion of the principal investigator, patients with any other known autoimmune disease that interferes with the accurate assessment of the clinical symptoms of CIDP. 12.a. Patients who received a live attenuated vaccine less than 28 days prior to screening. Reception of an inactivated, subunit, polysaccharide, or conjugate vaccine at any point prior to screening is not excluded. 13. Patients with a history of malignant tumors, unless considered cured by appropriate treatment, and with no evidence of recurrence for more than three years prior to the first dose of IMP. Patients with the following cancers may be included at any time: • Appropriately treated basal cell or squamous cell skin cancer, • Cervical intraepithelial neoplasia, • Carcinoma in situ of the breast, or • Incidental histological findings of prostate cancer (TNM [Tumor, Lymph Node, and Metastasis Classification] stage T1a or T1b). 14. Patients who previously participated in a trial with efgaltigimod and received at least one dose of IMP. 15. Patients with a known history of hypersensitivity to any of the components of IMP. 16. Patients with clinical evidence of other significant serious illnesses, or who have recently undergone or are scheduled to undergo major surgery, or for any other reason that could interfere with the results of the trial or put the patient at excessive risk.

[0507] 1.3.3 Prohibited Drug Therapy Drug therapy for CIDP was continued during the screening period but was discontinued after the start of the run-in period (RI-V1). • Intravenous or subcutaneous immunoglobulin therapy, Pulse corticosteroids and oral daily corticosteroids ≤ 10 mg / day.

[0508] The following drug therapies or treatments were not permitted to be administered throughout the trial period after ICF signing at the time of screening. ·Plasma exchange therapy, • Total lymphatic irradiation, • Any other IgG therapy, • Any stem cell-based therapy, including bone marrow transplantation such as autologous stem cell transplantation (ASCT) and allogeneic cell transplantation. • Any cytokine or anti-cytokine therapy, • Systemic corticosteroids, including oral preparations, used for purposes other than CIDP. Cyclophosphamide, interferon, tumor necrosis factor alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, or any other immunomodulatory or immunosuppressive drug or procedure. • Rituximab, alemtuzumab, or any other monoclonal antibody for immunomodulation. • Any investigational drug or experimental procedure, • Live attenuated vaccine Note: Acceptance of inactivated, subunit, polysaccharide, or conjugate vaccines at any point prior to screening was not prohibited. • Use of complementary therapies, including traditional Chinese medicine and herbal remedies, for any neurological condition within 4 weeks prior to IMP administration or within 5 half-lives (whichever is longer), and which has been agreed not to be used during the study.

[0509] 1.4 Research intervention The investigational drug products (IMPs) used in this study were as follows: -Open-label Stage A- Evgalchigimod PH20SC -Double-blind Stage B-Evgalchigimod PH20SC and placebo.

[0510] Efgalchigimod is a modified human IgG1 Fc fragment with increased affinity for human FcRn.

[0511] rHuPH20 is an enzyme used to increase the dispersion and absorption of co-administered therapeutic agents when SC is administered.

[0512] Efgaltigimod and rHuPH20 were co-formulated and administered as a single SC injection.

[0513] The fugartigimod PH20SC formulation was provided in vials at concentrations of 165 mg / mL or 180 mg / mL for fugartigimod, and at a concentration of 2000 U / mL for rHuPH20 (also referred to as ARGX-113 / rHuPH20). Each dose of fugartigimod PH20SC contained 1000 mg of fugartigimod. Note that there was a transition period using both formulations of fugartigimod PH20SC (containing fugartigimod at concentrations of 165 mg / mL or 180 mg / mL). After this transition period, all patients received the fugartigimod PH20SC formulation containing a higher concentration of 180 mg / mL of fugartigimod. The formulation with the higher concentration of fugartigimod (180 mg / mL) reduced the volume of each SC injection administered.

[0514] The placebo was a vehicle (containing rHuPH20 at 2000 U / mL) provided in a vial as a ready-to-use SC formulation. For both efgultigimod PH20 SC formulations (containing efgultigimod at concentrations of 165 mg / mL or 180 mg / mL), the corresponding placebo could be the same volume as the active drug and contained in the same vial.

[0515] A fixed dose of efgaltigimod PH20SC or PBO PH20SC was administered to the abdominal cutaneous area.

[0516] 1.5 Test Evaluation and Procedures Each participant was instructed to attend each research visit on the designated day, according to the activity schedule shown in Tables 9 and 10.

[0517] 1.5.1 Definition of clinically significant exacerbation during the run-in period, evidence of clinical improvement during Stage A, and aINCAT exacerbation during Stage B ECMD ECMD is defined as meeting any of the following criteria only during the run-in period. • The total aINCAT score increases by 1 or more points from the first visit during the run-in period (RI-V1), and / or • I-RODS decreases by 4 points or more from RI-V1 (using the centile metric), and / or • The average grip strength of one hand, measured using a handheld grip strength meter, decreases by 8 kPa or more from RI-V1. All patients who exhibited ECMD at the study site during the run-in period were immediately placed in Stage A.

[0518] ECI in Stage A patients who have not previously experienced this condition Patients whose aINCAT score worsened during the run-in period (an increase of 1 or more points compared to the first visit during the run-in period [RI-V1]) could only enter Stage B (a decrease of 1 or more points compared to the baseline [D1A] in Stage A) if they showed improvement in their aINCAT score during Stage A. These patients entered Stage B when improvement in their aINCAT score was confirmed.

[0519] Patients whose aINCAT score did not change during the run-in period, but whose I-RODS and / or grip strength worsened during run-in, may be admitted to Stage B if: If an improvement in the aINCAT score (a decrease of 1 point or more)...

Claims

1. A method for treating chronic inflammatory demyelinating polyneuropathy (CIDP) in a subject requiring treatment for CIDP, the method comprising administering an effective amount of a human neonatal Fc receptor (FcRn) antagonist to the subject.

2. The method according to claim 1, wherein the FcRn antagonist comprises two, three, or four FcRn binding regions.

3. The method according to claim 1 or 2, wherein the FcRn antagonist includes or consists of a variant Fc region or an FcRn binding fragment thereof.

4. The method according to claim 3, wherein the variant Fc region or its FcRn binding fragment binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region.

5. The method according to claim 3 or 4, wherein the variant Fc region or its FcRn binding fragment binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

6. The method according to any one of claims 3 to 5, wherein the variant Fc region includes or consists of a first Fc domain and a second Fc domain that form a homodimer or a heterodimer.

7. The method according to claim 6, wherein the first Fc domain and / or the second Fc domain contain amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively.

8. The method according to claim 6 or 7, wherein the first Fc domain and / or the second Fc domain contains amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

9. The method according to any one of claims 6 to 8, wherein the first Fc domain and / or the second Fc domain comprises an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO:

4.

10. The method according to any one of claims 6 to 9, wherein the first Fc domain and the second Fc domain include an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO:

4.

11. The method according to any one of claims 1 to 10, wherein the FcRn antagonist is efgartigimod.

12. The method according to claim 1, wherein the FcRn antagonist is an anti-FcRn antibody.

13. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is administered to the subject in a fixed dose of 200 mg to 20,000 mg.

14. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is administered to the subject at a dose of 2 mg / kg to 200 mg / kg.

15. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is administered to the subject in a fixed dose of about 800 to about 1200 mg.

16. The method according to claim 15, wherein the FcRn antagonist is administered to the subject in a fixed dose of approximately 1000 mg.

17. The method according to any one of claims 1 to 16, wherein the FcRn antagonist is administered subcutaneously.

18. The method according to any one of claims 1 to 17, wherein the FcRn antagonist is administered to the subject once a week.

19. The method according to any one of claims 1 to 17, wherein the FcRn antagonist is administered to the subject once every two weeks.

20. The method according to any one of claims 1 to 17, wherein the FcRn antagonist is administered to the subject once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

21. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1000 mg.

22. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is administered during the induction phase, followed by the maintenance phase, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of approximately 1000 mg during the induction phase, and the FcRn antagonist is administered subcutaneously once every two weeks at a fixed dose of approximately 1000 mg during the maintenance phase.

23. The method according to any one of claims 1 to 12, wherein the FcRn antagonist is initially administered subcutaneously at a fixed dose of approximately 1000 mg once a week, and thereafter, based on clinical evaluation, administered subcutaneously at a fixed dose of approximately 1000 mg once every two weeks.

24. The method according to claim 23, wherein a fixed dose of approximately 1000 mg is administered subcutaneously once a week, and this is resumed in response to worsening of symptoms.

25. The method according to any one of claims 1 to 16, wherein the FcRn antagonist is administered intravenously.

26. The method according to claim 25, wherein the FcRn antagonist is administered intravenously once a week or once every two weeks.

27. The method according to claim 25 or 26, wherein the FcRn antagonist is administered in a dose of approximately 3 mg / kg to approximately 60 mg / kg.

28. The method according to claim 27, wherein the FcRn antagonist is administered at a dose of 5 mg / kg.

29. The method according to claim 27, wherein the FcRn antagonist is administered at a dose of 10 mg / kg.

30. The method according to claim 27, wherein the FcRn antagonist is administered at a dose of 25 mg / kg.

31. The method according to any one of claims 1 to 21 and 25 to 30, wherein the FcRn antagonist is first administered intravenously and then subcutaneously.

32. The method according to any one of claims 1 to 31, wherein the FcRn antagonist is administered for a period of 61 weeks or less.

33. The method according to any one of claims 1 to 31, wherein the FcRn antagonist is administered for a period of 52 weeks or less.

34. The method according to any one of claims 1 to 31, wherein the FcRn antagonist is administered for a period of 48 weeks or less.

35. The method according to any one of claims 1 to 31, wherein the FcRn antagonist is administered for at least 12 weeks.

36. The method according to any one of claims 1 to 24, wherein the FcRn antagonist is administered subcutaneously once a week for at least four weeks.

37. The method according to claim 36, wherein the FcRn antagonist is administered subcutaneously once a week until the subject shows evidence of clinical improvement (ECI).

38. The method according to claim 36 or 37, wherein the FcRn antagonist is administered subcutaneously once a week until the subject exhibits an ECI during two consecutive measurements.

39. The method according to claim 37 or 38, wherein ECI is a clinical improvement in one or more of the following: Inflammatory Rush Construction Global Impairment Scale (I-RODS), mean grip strength, or Inflammatory Neuropathy Cause and Treatment (INCAT) score.

40. The method according to claim 36, wherein the FcRn antagonist is administered subcutaneously once a week until the subject shows evidence of clinically significant exacerbation (ECMD).

41. The method according to claim 40, wherein the ECMD is one or more of the following: an increase of 1 or more points in the adjusted INCAT (aINCAT) score, a decrease of 4 or more points in I-RODS (using centile metrics), or a decrease of 8 kPa or more in average grip strength in one hand using a handheld dynamometer.

42. The method according to claim 40 or 41, wherein the ECMD is an increase of one or more points in the aINCAT score.

43. The method according to any one of claims 40 to 42, wherein the ECMD is an increase of one or more aINCAT scores during two consecutive measurements.

44. The method according to any one of claims 40 to 43, wherein the ECMD is an increase of one or more points in the aINCAT score twice every two weeks.

45. The method according to any one of claims 40 to 44, wherein the ECMD is an increase of 2 or more points in the aINCAT score.

46. The method according to any one of claims 1 to 45, wherein the subject is diagnosed with CIDP according to the EFNS / PNS 2010 diagnostic criteria.

47. The method according to any one of claims 1 to 46, wherein the subject has a typical CIDP.

48. The method according to any one of claims 1 to 46, wherein the subject has a CIDP variant.

49. The method according to claim 48, wherein the subject has distal CIDP.

50. The method according to claim 48, wherein the subject has multifocal CIDP.

51. The method according to claim 48, wherein the subject has localized CIDP.

52. The method according to claim 48, wherein the subject has motile CIDP.

53. The method according to claim 48, wherein the subject has sensory CIDP.

54. The method according to any one of claims 1 to 53, wherein the subject has progressive CIDP.

55. The method according to any one of claims 1 to 53, wherein the subject has recurrent CIDP.

56. The method according to any one of claims 1 to 55, wherein the subject has an aINCAT score of 2 or more prior to administration of the FcRn antagonist.

57. The method according to any one of claims 1 to 55, wherein the subject has an aINCAT score of 5 or more before administration of the FcRn antagonist.

58. The method according to any one of claims 1 to 57, wherein the subject has an I-RODS centile metric score of 10 or more, optionally 20 or more, optionally 30 or more, optionally 40 or more, or optionally 50 or more before administration of the FcRn antagonist.

59. The method according to any one of claims 1 to 58, wherein the subject is newly diagnosed with CIDP.

60. The method according to any one of claims 1 to 58, wherein the subject is a patient who has never received treatment.

61. The method according to any one of claims 1 to 58, wherein the subject has previously received treatment for CIDP.

62. The method according to claim 61, wherein the subject has previously received steroid treatment.

63. The method according to claim 61 or 62, wherein the subject has previously received IVIg or SCIG treatment.

64. The method according to any one of claims 1 to 63, wherein the subject has an active disease despite treatment with corticosteroids or immunoglobulins.

65. The method according to any one of claims 1 to 64, wherein the subject is a CIDP patient characterized by the presence of an anti-NF155 antibody.

66. The method according to any one of claims 1 to 65, wherein the subject is a CIDP patient characterized by the presence of an anti-CNTN1 antibody.

67. The method according to any one of claims 1 to 66, wherein the subject is a CIDP patient characterized by the presence of an anti-Caspr1 antibody.

68. The method according to any one of claims 1 to 67, wherein the subject is a CIDP patient characterized by the presence of an anti-NF140 / 186 antibody.

69. The method according to any one of claims 1 to 68, wherein the subject is a CIDP patient characterized by the presence of an anti-GM-1 antibody.

70. The method according to any one of claims 1 to 69, wherein the subject is a CIDP patient characterized by the presence of an anti-LM-1 antibody.

71. The method according to any one of claims 1 to 70, wherein control of disease activity, partial remission, or complete remission is achieved after administration of the FcRn antagonist.

72. The method according to claim 71, wherein complete remission is achieved.

73. The method according to claim 71 or 72, wherein the control of disease activity, partial remission, or complete remission is achieved within 12 weeks, optionally within 8 weeks, optionally within 6 weeks, optionally within 4 weeks, or optionally within 3 weeks from the first administration of the FcRn antagonist.

74. The method according to any one of claims 71 to 73, wherein the control of disease activity, partial remission, or complete remission is sustained for at least two months in the subject.

75. The method according to any one of claims 71 to 73, wherein the control of disease activity, partial remission, or complete remission is sustained for at least six months in the subject.

76. The method according to claim 71, wherein, once the control of disease activity, partial remission, or complete remission is achieved, continued administration of the FcRn antagonist prevents exacerbation of symptoms.

77. The method according to claim 76, wherein the absence of symptom exacerbation is measured using one of the following: the INCAT score, the Medical Research Council (MRC) total score, the I-RODS, the mean grip strength test, or the Time-Up-and-Go (TUG) test.

78. The method according to any one of claims 1 to 77, wherein the treatment prevents or delays recurrence.

79. The method according to claim 78, wherein the treatment prevents or delays relapse for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks.

80. The method according to claim 78 or 79, wherein the treatment prevents or delays recurrence during the duration of treatment with the FcRn antagonist.

81. The method according to claim 78 or 79, wherein the treatment prevents or delays recurrence after discontinuation of treatment with the FcRn antagonist.

82. The method according to claim 81, wherein the treatment prevents or delays recurrence after discontinuation of the treatment for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks.

83. The method according to claim 81, wherein the treatment prevents or delays recurrence after discontinuation of the treatment for at least 20 weeks.

84. The method according to any one of claims 1 to 83, wherein the treatment reduces the risk of recurrence by at least 60%.

85. The method according to any one of claims 1 to 84, wherein the subject shows improvement in symptoms after administration of the FcRn antagonist when measured using the INCAT score, preferably when measured using the aINCAT score.

86. The method according to claim 85, wherein the subject exhibits a decrease of one or more points in the aINCAT score.

87. The method according to claim 85, wherein the subject exhibits a decrease of 2 or more points in the aINCAT score.

88. The method according to any one of claims 1 to 87, wherein the subject shows improvement in symptoms after administration of the FcRn antagonist, as measured using the total MRC score.

89. The method according to any one of claims 1 to 88, wherein the subject shows improvement in symptoms after administration of the FcRn antagonist when measured using the I-RODS.

90. The method according to claim 89, wherein the subject exhibits an increase of 4 points or more in the I-RODS centile metric score.

91. The method according to any one of claims 1 to 90, wherein the subject shows improvement in symptoms after administration of the FcRn antagonist when measured using the average grip strength test.

92. The method according to claim 91, wherein the subject exhibits an increase in average grip strength of 8 kPa or more.

93. The method according to any one of claims 1 to 92, wherein the subject shows improvement in symptoms after administration of the FcRn antagonist when measured using the TUG test.

94. The method according to any one of claims 85 to 93, wherein improvement of symptoms is achieved within 12 weeks, optionally within 8 weeks, optionally within 6 weeks, optionally within 4 weeks, or optionally within 3 weeks from the first administration of the FcRn antagonist.

95. The method according to any one of claims 1 to 94, wherein the subject exhibits a decrease in total IgG serum levels, autoantibodies, cytokines / chemokines, or immune complexes after administration of the FcRn antagonist.

96. The method according to claim 95, wherein the serum level of total IgG, the autoantibody, the cytokine / chemokine, or the immune complex is measured 4 weeks, 12 weeks, 24 weeks, or 48 weeks after administration of the FcRn antagonist.

97. The method according to claim 95 or 96, wherein the subject shows a decrease in serum levels of one or more autoantibodies selected from the group consisting of anti-GM1, anti-LM-1, anti-NF-155, anti-CNTN1, anti-Caspr-1 antibodies, and anti-myelinating nerve antibodies after administration of the FcRn antagonist.

98. The method according to any one of claims 1 to 97, wherein the subject does not show a decrease in serum albumin levels after administration of the FcRn antagonist.

99. The method according to any one of claims 1 to 98, wherein the subject does not show an increase in serum cholesterol after administration of the FcRn antagonist.

100. The method according to any one of claims 1 to 99, wherein the subject exhibits ECI after administration of the FcRn antagonist.

101. The method according to claim 100, wherein the subject exhibits ECI within 31 to 51 days after first receiving the FcRn antagonist.

102. The method according to claim 100 or 101, wherein the subject exhibits ECI within 43 days of first receiving the FcRn antagonist.

103. The method according to any one of claims 1 to 102, further comprising administering an effective amount of one or more additional therapeutic agents to the subject.

104. The method according to claim 103, wherein the additional therapeutic agent is a corticosteroid.

105. The method according to any one of claims 1 to 104, wherein the method is used to assist in the diagnosis of CIDP.

106. An FcRn antagonist for use in the treatment of CIDP according to the method of any one of claims 1 to 105.

107. Use of an FcRn antagonist in the manufacture of a pharmacopoeia for the treatment of CIDP, wherein the treatment is carried out according to the method described in any one of claims 1 to 105.

108. A method for treating CIDP in a patient population, A method comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once a week, wherein the patient population exhibits ECI in 66.5% of the subjects in the patient population after administration of efgultigimod PH20 or a biosimilar version thereof.

109. The method according to claim 108, wherein the patient population achieves the ECI within 31 to 51 days after first receiving the efgartigimod PH20 or a biosimilar version thereof.

110. The method according to claim 108 or 109, wherein the patient population achieves the ECI within 43 days of first receiving the efgartigimod PH20 or a biosimilar version thereof.

111. The method according to any one of claims 108 to 110, wherein the patient population includes 322 subjects.

112. The method according to any one of claims 108 to 110, wherein an anti-efgartigimod alpha antibody is detected in 6% of the patient population after administration of the efgartigimod PH20 for up to 12 weeks.

113. The method according to claim 112, wherein a neutralizing anti-efgartigimod alpha antibody is detected in 0.3% of the patient population after administration of the efgartigimod PH20 for up to 12 weeks.

114. The method according to any one of claims 108 to 110, wherein the subjects in the patient population remain recurrence-free for a significantly longer period than subjects who did not receive efgartigimod PH20 or a biosimilar version thereof.

115. The method according to any one of claims 108 to 110, wherein the subjects in the patient population experience a longer time to clinical exacerbation, which is statistically significant compared to subjects who did not receive efgaltigimod PH20 or a biosimilar version thereof, and the clinical exacerbation is an increase of one or more points in the aINCAT score.

116. The method according to claim 115, wherein the clinical exacerbation is an increase of one or more points in the aINCAT score during two consecutive measurements.

117. The method according to claim 115 or 116, wherein the clinical exacerbation is an increase of 2 points or more in the aINCAT score.

118. The method according to any one of claims 115 to 117, wherein the longer time to clinical exacerbation is indicated by a hazard ratio of 0.

394.

119. The method according to any one of claims 108 to 110, wherein the subjects in the patient population treated with efgaltigimod PH20 or a biosimilar version thereof show a 61% reduction in the risk of exacerbation in patients with CIDP.

120. A method for treating CIDP in a subject, A method comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once a week, wherein the subject exhibits an ECI after administration of efgultigimod PH20 or a biosimilar version thereof.

121. The method according to claim 120, wherein the subject achieves the ECI within 31 to 51 days after first receiving the efgartigimod PH20 or a biosimilar version thereof.

122. The method according to claim 120 or 121, wherein the subject achieves the ECI within 43 days of first receiving the efgartigimod PH20 or a biosimilar version thereof.

123. The method according to any one of claims 120 to 122, wherein the subject remains recurrence-free for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, or at least 20 weeks after administration of efgultigimod PH20 or a biosimilar version thereof.

124. The method according to any one of claims 120 to 123, wherein the subject exhibits a reduced risk of developing ECMD.

125. The method according to claim 124, wherein the ECMD is an increase of one or more points in the aINCAT score.

126. The method according to claim 124 or 125, wherein the ECMD is an increase of one or more aINCAT scores during two consecutive measurements.

127. The method according to any one of claims 124 to 126, wherein the ECMD is an increase of one or more points in the aINCAT score twice every two weeks.

128. The method according to any one of claims 124 to 127, wherein the ECMD is an increase of 2 or more points in the aINCAT score.

129. A method for treating CIDP in a patient population, A method comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once a week, wherein the mean percentage reduction in total IgG levels from baseline in the patient population after administration of efgultigimod PH20 or a biosimilar version is in the range of 66.8% to 71.6%.

130. The method according to claim 129, wherein the mean percentage reduction in total IgG levels from baseline was in the range of 66.8% to 71.6% in the patient population after administration of fgultigimod PH20 or its biosimilar version once weekly for a total of four doses.

131. The method according to claim 129 or 130, wherein the mean rate of decrease in total IgG levels from baseline was sustained from week 4 throughout the treatment period.

132. The method according to any one of claims 129 to 131, wherein the patient population includes 322 subjects.

133. A method for treating CIDP in a subject, A method comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once a week, wherein the subject exhibits a 66.8% to 71.6% decrease in serum total IgG levels after administration of efgultigimod PH20 or a biosimilar version compared to baseline levels before administration of efgultigimod PH20 or a biosimilar version.

134. The method according to claim 133, wherein the subject exhibits a 66.8% to 71.6% decrease in total serum IgG levels after being administered efgultigimod PH20 or a biosimilar version thereof once a week for a total of four times.

135. The method according to claim 133 or 134, wherein the decrease in the serum level of total IgG persists until the once-weekly administration of efgultigimod PH20 or its biosimilar version is discontinued.

136. A method for treating CIDP in a patient population, A method comprising administering 1008 mg / 11,200 units of efgultigimod PH20 or a biosimilar version thereof once a week, wherein the subjects in the patient population experience a longer time to clinical exacerbation, which is statistically significant compared to subjects who did not receive efgultigimod PH20 or a biosimilar version thereof, and the clinical exacerbation is an increase of 1 point or more in the aINCAT score.

137. The method according to claim 136, wherein the longer time to clinical exacerbation is indicated by a hazard ratio of 0.

394.

138. The method according to claim 136 or 137, wherein the patient population includes 221 subjects.

139. A method for treating CIDP in a subject requiring treatment for CIDP, the method comprising subcutaneously administering to the subject a clinically safe and effective dose of efgultigimod PH20 once a week.

140. The method according to claim 139, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously over a period of approximately 30 to 90 seconds.

141. The method according to claim 139 or 140, wherein the clinically proven safe and effective dose of efgartigimod PH20 is 1008 mg / 11,200 units.

142. The method according to any one of claims 139 to 141, wherein the subject shows evidence of improvement after administration of the fgultigimod PH20.

143. The method according to claim 142, wherein the subject shows evidence of improvement during two consecutive measurements.

144. The method according to claim 142 or 143, wherein the evidence of the improvement is selected from an improvement of one or more aINCAT points, an improvement of four or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

145. The method according to any one of claims 139 to 144, wherein the subject experiences a longer time to clinical exacerbation after administration of efgartigimod PH20 compared to a subject who has not received efgartigimod PH20.

146. The method according to claim 145, wherein the clinical exacerbation is an increase of 1 or more points in the aINCAT score.

147. The method according to claim 145 or 146, wherein the clinical exacerbation is an increase of one or more points in the aINCAT score during two consecutive measurements.

148. The method according to any one of claims 145 to 147, wherein the clinical exacerbation is an increase of one or more points in the aINCAT score twice in two weeks.

149. The method according to any one of claims 145 to 148, wherein the clinical exacerbation is an increase of 2 or more points in the aINCAT score.

150. A method for treating CIDP in a patient population, the method comprising subcutaneously administering a clinically safe and effective dose of efgultigimod PH20 once a week.

151. The method according to claim 150, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously over a period of approximately 30 to 90 seconds.

152. The method according to claim 150 or 151, wherein the clinically proven safe and effective dose of efgartigimod PH20 is 1008 mg / 11,200 units.

153. The method according to any one of claims 150 to 152, wherein, after administration of the patient population, 69% of the subjects in the patient population show evidence of improvement during two consecutive measurements.

154. The method according to claim 153, wherein the evidence of the improvement is selected from an improvement of one or more aINCAT points, an improvement of four or more I-RODS points, or an improvement of 8 kPa or more in average grip strength.

155. The method according to any one of claims 150 to 154, wherein the subjects in the patient population experience a longer time to clinical exacerbation compared to subjects who did not receive efgaltigimod PH20, and the clinical exacerbation is an increase of 1 point or more in the aINCAT score.

156. The method according to claim 155, wherein the clinical exacerbation is an increase of one or more points in the aINCAT score during two consecutive measurements.

157. The method according to claim 155 or 156, wherein the clinical exacerbation is an increase of 2 or more points in the aINCAT score.

158. The method according to any one of claims 155 to 157, wherein the longer time to clinical exacerbation is indicated by a hazard ratio of 0.

394.

159. The method according to any one of claims 155 to 157, wherein the patient population includes 221 subjects.

160. Efgultigimod PH20 for use in the treatment of CIDP in subjects requiring treatment of CIDP, wherein the clinically proven safe and effective dose of efgultigimod PH20 is administered subcutaneously to the subject once a week or once every two weeks.

161. Efgartigimod PH20 for use according to claim 160, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously once a week.

162. Efgartigimod PH20 for use according to claim 160, wherein the clinically safe and effective dose of efgartigimod PH20 is initially administered subcutaneously once a week, and thereafter, based on clinical evaluation, is administered subcutaneously once every two weeks.

163. Efgaltigimod PH20 for use according to claim 162, administered subcutaneously once a week, with the administration being resumed in response to worsening of symptoms.

164. Efgartigimod PH20 for use according to any one of claims 160 to 163, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously over a period of about 30 to 90 seconds.

165. Efgartigimod PH20 for use according to any one of claims 160 to 164, wherein the clinically safe and effective dose of efgartigimod PH20 comprises 1000 mg of efgartigimod alpha.

166. Efgaltigimod PH20 for use according to any one of claims 160 to 165, wherein the subject has an active disease despite treatment with corticosteroids or immunoglobulins.

167. Efgartigimod PH20 for use according to any one of claims 160 to 166, wherein the subject has received prior CIDP therapy prior to the initiation of efgartigimod PH20 treatment, and the efgartigimod PH20 is administered before the clinical effect of the prior CIDP therapy diminishes.

168. Efgultigimod PH20 for use according to claim 167, wherein the aforementioned prior CIDP therapy is a corticosteroid or immunoglobulin.

169. Efgartigimod PH20 for use according to any one of claims 160 to 168, wherein the subject exhibits a decrease in serum total IgG levels of 66.8% to 71.6% after administration of efgartigimod PH20 compared to baseline levels before administration of efgartigimod PH20.

170. Efgartigimod PH20 for use according to claim 169, wherein the subject exhibits a 66.8% to 71.6% decrease in total serum IgG levels after being administered efgartigimod PH20 once a week for a total of four times.

171. Efgartigimod PH20 for use according to claim 169 or 170, wherein the decrease in the serum level of total IgG persists until the once-weekly administration of efgartigimod PH20 is discontinued.

172. Efgartigimod PH20 for use according to any one of claims 160 to 171, wherein when efgartigimod PH20 is administered to a patient population subject to CIDP, it induces an ECI response in 66.5% of the subjects in the patient population.

173. Efgartigimod PH20 for use according to any one of claims 160 to 172, wherein the subject exhibits ECI after administration of efgartigimod PH20.

174. The evgartigimod PH20 for use according to claim 173, wherein the subject exhibits ECI within 31 to 51 days after first receiving the evgartigimod PH20.

175. Evgartigimod PH20 for use according to claim 173 or 174, wherein the subject exhibits ECI within 43 days of first receiving the evgartigimod PH20.

176. Efgartigimod PH20 for use according to any one of claims 160 to 175, wherein the subject remains recurrence-free for a significantly longer period after administration of efgartigimod PH20 compared to a subject who has not received efgartigimod PH20.

177. Efgartigimod PH20 for use according to any one of claims 160 to 176, wherein the subject shows a reduced risk of showing evidence of clinical exacerbation after administration of efgartigimod PH20.

178. Efgultigimod PH20 for use according to claim 177, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score.

179. Efgultigimod PH20 for use according to claim 177 or 178, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score during two consecutive measurements.

180. Efgaltigimod PH20 for use according to any one of claims 177 to 179, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score twice in two weeks.

181. Efgaltigimod PH20 for use according to any one of claims 177 to 180, wherein the evidence of the aforementioned clinical exacerbation is an increase of 2 or more points in the aINCAT score.

182. Efgultigimod PH20 for use in the treatment of CIDP in a patient population, wherein the treatment comprises subcutaneous administration of the efgultigimod PH20 at a clinically proven safe and effective dose once a week or once every two weeks.

183. Efgartigimod PH20 for use according to claim 182, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously once a week.

184. Efgartigimod PH20 for use according to claim 182, wherein the clinically safe and effective dose of efgartigimod PH20 is initially administered subcutaneously once a week, and thereafter, based on clinical evaluation, is administered subcutaneously once every two weeks.

185. Efgaltigimod PH20 for use according to claim 184, administered subcutaneously once a week, with the administration being resumed in response to worsening of symptoms.

186. Efgartigimod PH20 for use according to any one of claims 182 to 185, wherein the clinically safe and effective dose of efgartigimod PH20 is administered subcutaneously over a period of about 30 to 90 seconds.

187. Efgartigimod PH20 for use according to any one of claims 182 to 186, wherein the clinically safe and effective dose of efgartigimod PH20 comprises 1000 mg of efgartigimod alpha.

188. Efgaltigimod PH20 for use according to any one of claims 182 to 186, wherein the subject in the patient population has an active disease despite treatment with corticosteroids or immunoglobulins.

189. Efgartigimod PH20 for use according to any one of claims 182 to 188, wherein the subjects in the patient population have received prior CIDP therapy prior to the initiation of the efgartigimod PH20 treatment, and the efgartigimod PH20 is administered before the clinical effect of the prior CIDP therapy diminishes.

190. Efgultigimod PH20 for use according to claim 189, wherein the aforementioned prior CIDP therapy is a corticosteroid or immunoglobulin.

191. Efgartigimod PH20 for use according to any one of claims 182 to 190, wherein the mean percentage reduction from baseline in total IgG levels was in the range of 66.8% to 71.6% in the patient population after administration of efgartigimod PH20.

192. Efgartigimod PH20 for use according to claim 191, wherein the mean percentage reduction from baseline in total IgG levels was in the range of 66.8% to 71.6% in the patient population after administration of efgartigimod PH20 once weekly for a total of four doses.

193. Efgaltigimod PH20 for use according to claim 191 or 192, wherein the mean rate of reduction in total IgG levels from baseline was sustained from week 4 throughout the treatment period.

194. Efgartigimod PH20 for use according to any one of claims 182 to 193, wherein the patient population exhibits ECI in 66.5% of the subjects in the patient population after administration of efgartigimod PH20.

195. Efgartigimod PH20 for use according to claim 194, wherein the patient population achieves the ECI within 31 to 51 days after first receiving the efgartigimod PH20.

196. Efgartigimod PH20 for use according to claim 194 or 195, wherein the patient population achieves the ECI within 43 days of first receiving the efgartigimod PH20.

197. Efgartigimod PH20 for use according to any one of claims 182 to 196, wherein the subjects in the patient population remain recurrence-free for a significantly longer period than subjects who did not receive efgartigimod PH20.

198. Efgartigimod PH20 for use according to any one of claims 182 to 197, wherein the subjects in the patient population treated with efgartigimod PH20 show a 61% reduction in the risk of exacerbation.

199. Efgartigimod PH20 for use according to any one of claims 182 to 198, wherein the subjects in the patient population exhibit a reduced risk of showing evidence of clinical exacerbation after administration of efgartigimod PH20.

200. Efgultigimod PH20 for use according to claim 199, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score.

201. Efgultigimod PH20 for use according to claim 199 or 200, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score during two consecutive measurements.

202. Efgultigimod PH20 for use according to any one of claims 199 to 201, wherein the evidence of the aforementioned clinical exacerbation is an increase of one or more points in the aINCAT score twice in two weeks.

203. Efgaltigimod PH20 for use according to any one of claims 199 to 202, wherein the evidence of the aforementioned clinical exacerbation is an increase of 2 or more points in the aINCAT score.

204. Efgalchigimod PH20 for use according to any one of claims 182 to 203, wherein the patient population includes 322 subjects.

205. The method or use according to any one of claims 1 to 204, wherein the subject is an adult.

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