Laser system for treatment of hidradentis suppurativa

Abstract

A method of treating Hidradenitis Suppurativa (HS) using a 1726 nm laser pulse that selectively targets sebum produced by the sebaceous glands.

Description

LASER SYSTEM FOR TREATMENT OF HIDRADENTIS SUPPURATIVARELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 661 ,358 filed on June 18, 2024, the entire contents of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates to a method of treating Hidradenitis Suppurativa (HS) using a 1726 nm laser pulse that selectively targets sebum produced by the sebaceous glands.BACKGROUND

[0003] This invention relates generally to electromagnetic radiation-based medical treatment systems, and more specifically to delivering a laser pulse selectively to sebaceous glands in the treatment of Hidradenitis Suppurativa (HS).

[0004] Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease characterized by the development of painful nodules, abscesses, and tunneling wounds. Its global prevalence varies between 0.03% and 4%, significantly impacting the quality of life for affected individuals. The etiology of HS remains unclear, creating a clinical challenge in developing effective treatments (Goldburg SR, et al. Hidradenitis suppurativa: Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol. 2020 May;82(5): 1045-1058).

[0005] Recent advancements in anti-inflammatory medications undergoing FDA approval have shown promise in targeting nodular disease. However, their efficacy is suboptimal, and also present risks of infections lymphoma, while requiring high costs. These medications also tend to lose efficacy over time, necessitating nearly lifelong use.

[0006] Current interventions, including antimicrobials, hormone modulators, and behavioral adjustments, have proven insufficient, leaving a significant clinical gap.

[0007] A major clinical gap exists, with HS being both prevalent and negatively impactful on patients and the healthcare system. The suboptimal nature of existing and pipeline therapies highlights the urgency to rethink HS treatment strategies.Early recognition and intervention are crucial for a favorable prognosis, but the current lack of effective early-stage management exacerbates the suffering of many individuals with HS. The tragic reality emerges that many individuals with HS suffer silently, underscoring the critical need for early-stage management solutions.

[0008] In this context, there is an immediate need for targeted approaches to address the limitations of existing treatments.SUMMARY

[0009] The embodiments of the present disclosure provide a method of treating Hidradenitis Suppurativa (HS) in a patient comprising irradiating a HS nodule with a spot or spots of a therapeutic laser pulse having a wavelength of about 1726 nm, and wherein the treatment resulted in improvement in the nodule as compared to baseline prior to treatment.

[0010] In some aspects, the patient undergoing the treatment is diagnosed with Hurley Scale Stage 1 HS or Hurley Scale Stage 2 HS.

[0011] In some aspects, the patient is diagnosed with HS on one or more of axilla, inguinal, groin, anogenital region, the areola or nipple of the female breast, the eyelids (Moll's glands), the external auditory canal, skin of the scalp and the face, or in areas where the skin rubs together, such as the armpits, groin, buttocks and breast areas.

[0012] In some aspects, the patient is diagnosed with HS in an area rich with apocrine glands, in an area with hair follicle blockage, or in areas with apocrine glands in a friction zone of the body.

[0013] In some aspects, the area rich with apocrine glands is the axilla or groin, anogenital region, the areola and nipple of the female breast, the eyelids (Moll's glands), and the external auditory canal, and skin of the scalp and the face, and in areas where the skin rubs together, such as the armpits, groin, buttocks, breasts, and waistband area, back of the neck, behind the ears, and around the nape of the neck.

[0014] In some aspects, the patient is treated at leaset one time and up to five times.

[0015] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline, wherein there is an improvement over basline after the first and / or second treatment..

[0016] In some aspects, one measure of the HiSCR is a measure of the baseline total abscess and inflammatory nodule count (AN count).

[0017] In some aspects, the patient has a one grade improvement on the HiSCR scale after being treated; or wherein the patient has a two grade improvement on the HiSCR scale after being treated.

[0018] In some aspects, the patient has a 50% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

[0019] In some aspects, the patient has a 25% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

[0020] In some aspects, the patient has no increase in nodule or abscess count after the treatment.

[0021] In some aspects, the patient is evaluated for pain level during the treatment using the 11 -point (0-10) Visual Analog Pain Scale.

[0022] In some aspects, the patient is evaluated for change in lesion count.

[0023] In some aspects, the lesion count include abscesses, nodules and tunnels.

[0024] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline.

[0025] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline.

[0026] In some aspects, the Hurley Stage is Stage 1 , Stage 2 or Stage 3.

[0027] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 4 weeks, after final treatment.

[0028] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 12 weeks after final treatment.

[0029] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 24 weeks after final treatment.

[0030] In some aspects, the patient is evaluated for change in lesion count compared to baseline at about 4 weeks, about 12 weeks, and about 24 weeks after final treatment.

[0031] In some aspects, wavelength is from about 1710 nm to about 1735 nm.

[0032] In some aspects, the wavelength is from about 1720 nm to about 1730 nm.

[0033] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 4 weeks after final treatment, wherein the final treatment can be the first, second, third, forth or fifth treatment.

[0034] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 12 weeks after final treatment.

[0035] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 24 weeks after final treatment.

[0036] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline at about 4 weeks after final treatment.

[0037] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline at about 12 weeks after final treatment.

[0038] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline at about 24 weeks after final treatment.

[0039] The treatment disclosed herein applies to patients with Fitzpatrick skin types I- VI.

[0040] The patient undergoing the treatment disclosed herein is atleast 12 years of age or older.

[0041] In some aspects, the patient is aged between 12 and 80 years.

[0042] In some aspects, the patient has improvement in or full resolution in one or more of pain, itching, drainage or odor.

[0043] The embodiments of the present disclosure provide a method of treating Hidradenitis Suppurativa (HS) in a patient comprising irradiating a sebum or a sebaceous gland with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and wherein the treatment resulted in a reduction of inflammatory lesion count.

[0044] In certain embodiments, the wavelength is about 1726 nm and can be from about 1710 nm to about 1735 nm. In certain embodiments, the wavelength can be from about 1720 nm to about 1730 nm.

[0045] In some aspects, the patient undergoing the treatment is diagnosed with Hurley Scale Stage 1 HS or Hurley Scale Stage 2 HS.

[0046] In the methods of the disclosure, the patient is diagnosed with HS on left and right axilla and on left and right inguinal areas.

[0047] In some aspects, the patient is diagnosed with HS in an area rich with apocrine glands or in an area with hair follicle blockage.

[0048] In some aspects, the area rich with apocrine glands is the axilla or groin, anogenital region, the areola and nipple of the female breast, the eyelids (Moll's glands), and the external auditory canal, and skin of the scalp and the face, and in areas where the skin rubs together, such as the armpits, groin, buttocks and breasts.

[0049] In some aspects, the patient is treated one more times.

[0050] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline.

[0051] In some aspects, one measure of the HiSCR is a measure of the baseline total abscess and inflammatory nodule count (AN count).

[0052] In some aspects, the patient has a one grade improvement on the HiSCR scale after being treated; or wherein the patient has a two grade improvement on the HiSCR scale after being treated.

[0053] In some aspects, the patient has a 50% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

[0054] In some aspects, the patient has a 25% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

[0055] In some aspects, the patient has no increase in abscess count after the treatment.

[0056] In some aspects, the patient is evaluated for pain level during the treatment using the 11 -point (0-10) Visual Analog Pain Scale.

[0057] In some aspects, the patient is evaluated for change in lesion count compared to baseline, wherein the lesion count include abscesses, nodules and tunnels.

[0058] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline.

[0059] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline. The Hurley Stage is Stage 1 , Stage 2 or Stage 3.

[0060] In some aspects, the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 4 weeks, about 12 weeks, and about 24 weeks after final treatment.

[0061] In some aspects, the patient is evaluated for change in lesion count compared to baseline at about 4 weeks, about 12 weeks, and about 24 weeks after final treatment.

[0062] In some aspects, the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 4 weeks, about 12 weeks, and about 24 weeks after final treatment.

[0063] In some aspects, the patient is evaluated for change in Hurley Stage compared to baseline at about 4 weeks, about 12 weeks, and about 24 weeks after final treatment.

[0064] The treatment disclosed herein applies to patients with Fitzpatrick skin types I- VI.

[0065] The patient undergoing the treatment disclosed herein is atleast 18 years of age or older.

[0066] In some aspects, the patient is aged between 18 and 60 years.BRIEF DESCRIPTION OF THE DRAWINGS

[0067] FIG. 1 is a flow chart of the treatment cycle.

[0068] FIG. 2 is a flowchart for classification of adverse device effects.

[0069] FIG. 3 is a 11 -point VAS Pain Rating Scale.

[0070] FIG. 4 shows photographs of patients affected with HS. FIG. 4A and FIG. 4B are photographs of arm pits showing the inflammation of a patient affected with HS. FIG. 4C is a photograph of area between the breasts showing the inflammation of a patient affected with HS.

[0071] FIG. 5 shows photographs pre-treatment and post treatment. FIG. 5A shows basline right groin and the same spot two months after baseline and after two treatments. FIG. 5B shows the left goin (untreated control) from the same patient at the same timepoints. In FIG. 5A there is visible improvement in the lesions after the two treatments and in FIG. 5B there is visible worsening of the lesions. FIG. 5C shows the legend for lesion tracking.

[0072] FIG. 6 is a diagram of two examples of treatment patterns or spots for the large handpiece. FIG. 6A is a diagram of 2x2 treatment pattern or spots for the large handpiece. FIG. 6B is a diagram of 5x5 treatment pattern or spots for the large handpiece.DETAILED DESCRIPTION

[0073] Exemplary embodiments of the present disclosure are illustrated in the drawings, which are illustrative rather than restrictive. No limitation on the scope of the technology, or on the claims that follow, is to be implied or inferred from the examples shown in the drawings and discussed herein.

[0074] Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent deep-seated nodules & abscesses that rupture, leading to formation of sinus tracts & fibrotic scars. It most commonly in areas rich with apocrine glands (e.g., axilla, groin). Pain, drainage, odor, and scarring cause negative social impact.

[0075] HS occurs when the hari follicles and nearby aprocrine glands (sweat glands) on the underarms, groin, buttocks and under the breasts become infection and inflamed.

[0076] HS affects approximately 1 to 4% of population. The prevalence of HS is likely higher due to often-delayed diagnosis. HS is more common among women.

[0077] The traditional treatment for HS has been challenging, often involves a multidisciplinary approach. Early stage treatments include topical clindamycin, intralesional corticosteroid injections, topical resorcinol, certain systemic antibiotics, anti-androgen therapy, acitretin, systemic corticosteroids, and partial de-roofing.

[0078] Later stage treatments include wide exicision surgery and immune suppressing biologies.

[0079] The primary pathogenic event in HS, in part, is believed to be infundibular hyperplasia resulting from intrinsic keratinocyte defects, leading to cyst formation and rupture (Goldburg SR, et al. Hidradenitis suppurativa: Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol. 2020 May;82(5):1045-1058, Smith SDB, et al. Histopathology of Hidradenitis Suppurativa: A Systematic Review. Dermatopathology (Basel). 2022 Jul 14;9(3):251-257). The subsequent acute inflammatory cascade evolves into a chronic process. Fibrosis in late-stage HS obliterates sebaceous glands, suggesting their role as a nidus for disease progression (Smith SDB, et al. Histopathology of Hidradenitis Suppurativa: A Systematic Review. Dermatopathology (Basel). 2022 Jul 14;9(3):251-257). Previous studies utilizing lasers and energy-based devices targeting this unit have shown promise (Hamzavi IH, et al. Laser and light-based treatment options for hidradenitissuppurativa. J Am Acad Dermatol. 2015 Nov;73(5 Suppl 1 ):S78-81 ). Laser hair removal, radiofrequency and intense pulsed light (IPL) have all been shown to diminish disease flares in HS. However results have been inconsistent and often not clinically important, highlighting the need for newer targeted approaches.

[0080] This disclosure relates to treatment of Hidradenitis Suppurativa (HS) in a patient. It involves using a laser light pulse of about 1726 nm to target sebum produced by overactive sebaceous glands in a non-invasive manner. Without wishing to be bound by any theory, it is believed that the laser system selectively target the sebaceous glands and also target the apocrine glands through controlled heating.

[0081] A potential benefit of laser treatment is reduction in severity of HS.

[0082] Definitions

[0083] Applicant specifically incorporates the entire contents of all cited references in this disclosure. Further, when an amount, concentration, or other value or parameter is given as either a range or a list of upper values and lower values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or value and any lower range limit or value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the present disclosure be limited to the specific values recited when defining a range.

[0084] The indefinite articles “a” and “an”, as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one”.

[0085] The phrase “and / or”, as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open- ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A(optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0086] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of’, or, when used in the claims, “consisting of”, will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, “either”, “one of”, “only one of’, “exactly one of”. “Consisting essentially of”, when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0087] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1 %, or ±0.1 % from the specified value, as such variations are appropriate to perform the disclosed methods.

[0088] The term “Adverse Event (AE)” refers to any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in clinical study subjects, device users or other persons, whether or not related to the medical device.

[0089] Reported AE: Adverse events (AE) will be categorized as serious and non- serious, device-related and non-device-related, and anticipated and unanticipated. All reported AEs should be followed until resolution. In the unusual circumstance that an AE has not resolved by the time of the subject’s completion of the study, an explanation will be entered on the appropriate eCRF (case report form).

[0090] The frequency of each event will be summarized by seriousness, severity and by relationship to the device. Since some subjects may report the same event several times, the first occurrence of the worst reported case of the event will be used for the purpose of analysis.

[0091] The term “Adverse Device Effect (ADE)” refers to any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (includingabnormal laboratory findings) in subjects, device users or other persons, related to the medical device.

[0092] The term “Serious Adverse Event (SAE)” refers to any adverse event that led to a death, led to a serious deterioration in the health of the subject that: resulted in a life-threatening illness or injury; resulted in a permanent impairment of a body structure or body function; required in-patient hospitalization or prolongation of existing hospitalization; and resulted in medical or surgical intervention to prevent permanent impairment to a body structure or a body function, and led to fetal distress, fetal death or a congenital abnormality or birth defect. Any ADE that has resulted in any of the consequences characteristic of a serious adverse event (as described above) is considered a serious adverse device effect (SADE).

[0093] The term “anticipated serious adverse device effect (ASADE)” is any SADE on health or safety, or any life-threatening problem or death caused by, or associated with the device, if that effect, problem, or death was previously identified in nature, severity, or degree of incidence in the study plan, operator manual, or regulatory application; or any other serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

[0094] The term “Unanticipated Serious Adverse Device Effect (USADE / UADE)” is any SADE on health or safety or any life-threatening problem or death caused by, or associated with the device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan, operator manual, or regulatory application; or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

[0095] In subjects, the ADEs / SADEs include the effects related to the investigational medical device (clinical study device), or the procedures involved. For device users or other persons (e.g., other clinical staff in the treatment room) ADE / SADE is restricted to the effects related to investigational medical devices.

[0096] ADEs / SADEs may include the effects (1 ) resulting from insufficient or inadequate instructions for use, deployment, installation, or operation, or any malfunction of the investigational medical device; (2) resulting from user error or from intentional misuse of the investigational medical device.

[0097] Adverse Event / Adverse Device Effect (AE / ADE) Severity: The severity of an effect will be rated according to the following definitions:Mild', requires minimal or no treatment and does not interfere with the Subject’s daily activities.Moderate', may cause some interference with functioning.Severe', interrupts Subject’s usual daily activity and may require treatment.

[0098] Adverse Event / Adverse Device Effect (AE / ADE) Relationship to Device: The relationship of an event to study device will be determined as follows:Unrelated: The event is clearly related to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant drugs administered to the subject. Possible: The event follows a reasonable temporal sequence from the time of device administration but could have been produced by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs.Probable: The event follows a reasonable temporal sequence from the time of device administration and follows a known response pattern to the device. The event cannot be reasonably explained by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs.Definite: The event follows a reasonable temporal sequence from the time of device administration and follows a known response pattern to the device. The event cannot be reasonably explained by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs AND either occurs immediately following device administration, improves on stopping device administration, or reappears on re-exposure of device administration. The classification of adverse device effects is shown in the flowchart in FIG. 2.

[0099] As used herein, “target skin area” or “target area” refers to the skin receiving the energy of a laser pulse. The target skin area may include the surface skin area illuminated by the laser pulse, as well as deeper structures beneath the surface skin that receive at least a portion of the energy from the laser pulse. As such, “target skin areas” treated by a laser pulse may refer to a volume of skin as opposed to a true area of an outer surface of the epidermis.

[0100] As used herein, “Fitzpatrick skin type” also referred as “Fitzpatrick scale” is a numerical classification scheme for human skin color and is a well-recognized tool for dermatological research.

[0101] HiSCR Score: The Hidradenitis Suppurativa Clinical Response (HiSCR) is defined as a > 50% reduction in inflammatory lesion count (abscesses + inflammatory nodules), and no increase in abscesses or draining fistulas whencompared with baseline. It has been recently used to assess the effectiveness of treatment with biologies.

[0102] The Hurley Clinical Staging for Hidradenitis Suppurativa is defined as in Table 1.

[0103] Table 1 : Hurley Clinical Staging for Hidradenitis Suppurativa.

[0104] IHS4 Score: The International Hidradenitis Suppurativa Severity Score System (IHS4) score is defined Table 2 (Kimball AB, et al. Assessing the validity, responsiveness and meaningfulness of the hidradenitis suppurativa clinical response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol 2014; 171 : 1434-42) and (Zouboulis CC, et al. European Hidradenitis Suppurativa Foundation Investigator Group. Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity. Br J Dermatol. 2017 Nov;177(5):1401-1409).

[0105] Table 2: IHS4 Score.

[0106] As used herein, the terms “treat,” “treating” or “treatment” refer to an action to obtain a beneficial or desired clinical result including, but not limited to, alleviation or amelioration of one or more signs or symptoms of Hidradenitis Suppurativa (HS). In certain embodiments, the efficacy of the treatment by a qualified individual, e.g., a dermatologist, can be evaluated using accepted assessment tools of pain and quality of life (QOL) such as, but not limited to Global Aesthetic Improvement Scale (GAIS), 11 -point (0-10) Visual Analog Pain Scale, and assessment for Adverse Events. Quality of Life (QOL) Questionnaire also request informion from a patient on bother from pain, itching, drainage and odor of the lesions. A decrease in any one of pain, itching, drainage or odor is desirable. A subject may see a decrease orimprovement of, or full resolution in one or more of pain, itching, drainage or odor of a nodule within days to weeks after the first treamtment, within days to weeks after the second treatment, within days to weeks after the third treatment, within days to weeks after the forth treatment, or within days to weeks after the fifth treatment. The decrease or improvement, is any decrease or improvement over baseline as described by the patient. The decrease or improvement can also be a measure on a scale as reported by the patient.

[0107] Dermatological systems and methods for providing a therapeutic laser treatment are disclosed in US 10,864,380 B1 , US 11 ,253,720 B2, US 11 ,400,308 B2, US 11 ,738,206 B2, US 2022 / 0168590 A1 , US 2022 / 0212026 A1 , US 2022 / 0212027 A1 , and US 2023 / 0302294 A1 ; each of which incorporated by reference herein in its entirety.EXAMPLES

[0108] Example 1

[0109] Therapeutic Laser. The method of treating Hidradenitis Suppurativa (HS) disclosed herein employs a therapeutic laser having a wavelength of about 1726 nm to irradiate a sebum or a sebaceous gland with a spot of a laser pulse.

[0110] The laser system used herein is Cutera® 1726 nm laser system, also referred to as “1726 Laser System”. This laser system is indicated for the long-term treatment of mild to severe inflammatory acne vulgaris (K230660) (Scopelliti MG, et al. A novel 1726-nm laser system for safe and effective treatment of acne vulgaris. Lasers Med Sci. 2022 Dec;37(9):3639-3647).

[0111] We hypothesize that by selectively targeting and destroying this nidus for disease, the 1726 nm laser will lead to a significant reduction in disease flares and halt the progression to later stages of HS. An infrared diode laser device uses pulsed laser energy at a wavelength of 1726 nm. The treatment spot size, beam characteristics, tissue absorption and scattering coefficients at the output wavelength define the tissue penetration depth of the delivered energy. When combined with pre, parallel (during energy delivery), and post cooling of epidermal and superficial dermal structures, selective heating of dermal tissue at different depths is enabled. The device has shown great promise in moderate to severe acne vulgaris (Bittar J, et al. 1726 nm Lasers for the Treatment of Acne Vulgaris. Skin Therapy Lett. 2024 Jan;29(1 ):5-7; Goldberg DJ, et al. Treatment of mild to severeacne with 1726 nm laser: A safe alternative to traditional acne therapies. J Cosmet Dermatol. 2023 Nov;22(11 ):3026-3032; Goldberg D, et al. Selective photothermolysis with a novel 1726 nm laser beam: A safe and effective solution for acne vulgaris. J Cosmet Dermatol. 2023 Feb;22(2):486-496; and Alexiades M, et al. Novel 1726 nm laser demonstrates durable therapeutic outcomes and tolerability for moderate-to-severe acne across skin types. J Am Acad Dermatol. 2023 Oct;89(4):703-710).

[0112] The pre-cooling time to be sufficient to effectively cool the superficial structure of the skin, namely the epidermis and superficial dermis, but not so long for the sebaceous glands to be cooled. Thus, there are safety algorithms contained in the 1726 Laser System software to ensure that the appropriate amount of cooling is applied to the skin before, during and after the laser pulse is administered.

[0113] Cooling prior to the pulse (1 second of pre-cooling) acts as an anesthetic and protects the epidermis and superficial dermis from the irradiation of the laser pulse. Cooling during the energy delivery (parallel cooling) further protects the epidermis and the superficial dermis. Cooling after the pulse (1 second to 20 seconds of postcooling) prevents thermal injury to the epidermis and superficial dermis from the thermal blooming (conducted energy) that diffuses from the sebaceous glands. The 1726 nm laser energy when coupled with the appropriate amount of skin cooling selectively heats the sebum in the sebaceous gland in the dermis while simultaneously protecting the epidermis and superficial dermis, resulting in controlled thermal injury of the glands and thus the reduction of sebum production.

[0114] During treatment, the operator may interact with the console via the touchscreen user interface which presents the controls used by the Investigator (or qualified designee) to monitor and set the system status (including “Off”, “Standby” and Ready” modes) and treatment parameters. The operator adjustable treatment parameters include the treatment fluence, spot pattern, and the skin contact cooling window temperature. The touchscreen user interface also presents other displays and indicators to ensure safe and accurate operation. After the device is in “Ready” mode and the footswitch is depressed, treatment is applied using a stamping method, meaning that the temperature-controlled treatment window is pressed against the skin with sufficient firm and even pressure to initiate cooling prior to, during, and post laser energy application. Following a 1 second pre-cooling delay, energy delivery to the treatment spots (in the selected spot pattern), and a 2 secondpost-cooling delay, the system generates an audible signal to the user to lift the hand piece and move to the adjacent area and the process is repeated as shown in the flow chart in FIG. 1.

[0115] The use of 1726 nm laser in HS treatment offers a transformative approach to address the unmet needs of individuals living with this debilitating condition.

[0116] Potential Risks: Possible risks or ADEs associated with 1726nm laser treatment or similar laser devices / procedures are listed as follows: edema, erythema, heat sensation during treatment, pain or discomfort during treatment, skin dryness, textural changes, blistering, scabbing / crusting, hyperpigmentation, hypopigmentation, infection, oozing (serum or plasma), pruritus, scarring, transient acne flareups, harmful eye exposure to light energy, altered hair growth in treatment area, bleeding, small papules, burn, and erosions.

[0117] Possible risks also include unintended injury to subject, user, or others due to user error (e.g., unintentional treatment to non-target location) or equipment problem (e.g., device malfunction). Subjects will be asked to wear eye protection during the laser procedure to prevent eye damage.[01181 Example 2

[0119] Study Design. This is a single-center, prospective, randomized, placebo- controlled study. One study site will enroll and initiate treatment on up to 8 male and female subjects, ages 18 to 60 years, who present with HS on left and right axilla and / or inguinal area at baseline, and pass all eligibility criteria. Enrolled subjects will receive 3 laser treatments at 4 (±1 ) week intervals. Subjects will be followed at approximately 4 (±1 ) week post-treatment completion (via phone) at 12 (± 2) weeks and 24 (± 3) weeks post treatment completion onsite.

[0120] Standardized digital photographs will be taken of each subject’s left and right axilla and / or inguinal area at screening / baseline, prior to all laser treatments and the 12- and 24- weeks post final treatment followup visits.

[0121] A summary of all study required procedures and assesments can be found in Table 3.

[0122] Table 3: Study Schedule.Trior to the laser treatment,2Confirm still meets,3May alos be conducted post treatment, Trior to laser treatment 1 only,5After confirmation of eligibility, and6At 12- or 24-weeks post final treatment follow-up.

[0123] Subjects will use an approved mild cleanser and daily sunscreen on the face of SPF 30 or higher, and will be asked to practice strict, diligent prevention of sun exposure.

[0124] Example 3

[0125] Study Duration. Subjects enrolled in this study will participate for up to approximately 40 weeks and complete up to 7 visits.1 screening / baseline visit;3 treatment visits at 4 (± 1) week intervals;1 follow-up visit via phone at approximately 4 (± 1 ) weeks post final treatment;2 on-site follow-up visits at 12 (± 2) weeks and 24 (± 3) weeks post final treatment.

[0126] Example 4

[0127] Study Outcome Measures

[0128] Primary Endpoint: HiSCR

[0129] Secondary Endpoint:1. Treatment site pain (pretreatment, immediately post, at follow up visits)2. Change in lesion counts (abscesses, nodules, tunnels)3. Change in IHS44. Change in Hurley Stage

[0130] Exploratory Endpoints:1 . Number of disease flares in each treatment site2. Effect on microbiome (whole genome shotgun sequencing)3. Quality of life (QOL, DLQI, HiSQOL)4. Histological tissue changes and change in a pro-inflammatory gene expression signature by Nanostring nCounter panel

[0131] Table 4 provides a summary of the outcomes, measure description and time frame.

[0132] Table 4: Outcome Measures and Time Frames.

[0134] Study Outcome Measures - Safety

[0135] Overall safety of the Cutera® 1726 nm laser system for the treatment of Hidradenitis Suppurativa will be assessed by a review of the totality of all reported adverse events and discomfort during treatment administration as rated by the subject using the 11 -point (0 to 10) Visual Analog Pain Scale will also be assessed.[01361 Example 6

[0137] Effectiveness Assessments

[0138] Improvement in HS severity as measured by HiSCR and IHS4 as well as subject questionnaires at baseline and at all onsite follow-up visits (12- and 24- weeks post-final treatment). Subjects will be asked to complete DLQI, QOL, and HiSQOL to assess their level of satisfaction with the laser treatment outcome and the overall laser treatment procedure, and evaluate overall quality of life measures.

[0139] Example 7

[0140] Safety Assessments i) Incidence and Severity of Adverse Events: Following the first treatment, adverse events (AEs) / adverse device effects (ADEs) will be assessed posttreatment and at each subsequent subject visit. ii) Treatment-related Discomfort: Immediately post each treatment, subjects will be asked to rate the average amount of discomfort experienced during treatment using the 11 -point VAS Pain Rating Scale (0-10) as shown in FIG. 3.

[0141] Example 8:

[0142] a) Screening and Baseline Procedures.

[0143] The following procedures will occur:

[0144] 1. Informed Consent

[0145] 2. Assess and document study eligibility (inclusion / exclusion) criteria.

[0146] 3. Collect and document demographic information.

[0147] 4. Assess and document medical history.

[0148] 5. Assess and document concomitant prescription or over-the-counter medications (including vitamins / herbs / supplements) currently using or used within the past 30 days.

[0149] 6. Assess and document concomitant skincare products used on the left and right axilla and / or inguinal area.

[0150] 7. Record date of last menstrual cycle for women of childbearing potential (WOCBP).

[0151] 8. Cleanse treatment area with an Investigator approved mild cleanser.

[0152] 9. Investigator (or qualified designee) will assess the subject’s left and right axilla and / or left and right inguinal area.

[0153] 10. Trained staff will take standardized digital photographs of the subject’s left and right axilla and / or left and right inguinal area

[0154] 11. The before and after treatment instructions will be explained and provided to the subject.

[0155] b) Treatment Visit Procedures

[0156] Three (3) treatment visits will occur at 4 (± 1) week intervals.

[0157] i) Pre-Treatment Procedures: The following procedures will occur prior to beginning of each treatment:

[0158] 1. Confirm subject continues to meet the study eligibility criteria.

[0159] 2. Prior to treatment 1 , assess and record any changes to subject’s medical history since the previous study visit.

[0160] 3. Assess and record any additions, changes and / or deletions in prescription and over-thecounter concomitant medications (including vitamins / herbs / supplements) since the previous study visit.

[0161] 4. Assess and record any additions, changes and / or deletions in concomitant skincare products used on the left and right axilla and / or inguinal area since the previous study visit.

[0162] 5. Record date of last menstrual cycle for WOCBP.

[0163] 6. At treatment visit 1 , subject will complete and return the Baseline Questionnaires.

[0164] 7. Prior to treatment 1 , one axilla and / or inguinal area will be assigned as treatment (Experimental Arm) and the other will be assigned as a control (Control Arm).

[0165] 8. Prior to treatment 1 , a punch biopsy may or may not be obtained from the treatment assigned area for baseline.

[0166] 9. Cleanse treatment area with an Investigator approved mild cleanser.

[0167] 10. At treatment visit 2 and 3, assess for any new adverse events / adverse device effects (AEs / ADEs) or changes to previously recorded AEs / ADEs.

[0168] 11. Trained staff will take pre-treatment standardized digital photographs of the subject’s left and right axilla and / or inguinal area.

[0169] 12. The Investigator (or qualified designee) will assess the left and right axilla and / or inguinal area.

[0170] ii) Treatment Procedures: Subjects will receive a treatment with the investigational Cutera® 1726 nm laser system as follows:

[0171] 1. The subject and the staff in the laser treatment area must wear appropriate laser protective eyewear with an optical density sufficient to protect from the 1726 nm treatment wavelength.

[0172] 2. The subject may or may not sit for 30 minutes with topical 5% lidocaine in aqueous base for anesthesia. After 30 minutes, the area will be cleansed.

[0173] 3. The subject should be lying down and comfortable while undergoing the laser treatment and the operator (Investigator or qualified designee) should have easy access to both the device and the subject’s assigned treatment area.

[0174] 4. The operator (Investigator or qualified designee) will prepare the patient and conduct treatment using the Cutera® 1726 nm laser system according to the operator manual. All operator adjustable laser treatment settings will be selected at Investigator’s (or qualified designee’s) discretion.

[0175] 5. The laser serial number, treatment settings used, and time of treatment will be recorded. The treatment may be video recorded.

[0176] 6. Immediately post treatment, the subject will be asked to rate the level of discomfort felt during the treatment using the 11 -point VAS Pain Rating Scale shown in FIG. 3.

[0177] 7. The Investigator (or qualified designee) will assess the post-treatment adverse device effects (ADEs).

[0178] 8. Designated staff will remind the subject of after-treatment care instructions.

[0179] 9. Trained staff may take post treatment photographs of the subject’s left and right axilla and / or inguinal area.

[0180] 10. The device shall be cleaned / disinfected between uses according to the instructions specified in the operator manual.

[0181] c) Follow-Up Visit Procedures

[0182] Follow-up visits will occur at approximately 4 (± 1 ) weeks post final treatment (via phone), and at 12 (± 2) and 24 (± 3) weeks post final treatment on-site.

[0183] The following procedures will be performed at all follow-up visits:

[0184] 1. Confirm subject continues to meet the study eligibility criteria.

[0185] 2. Assess and record any additions, changes and / or deletions in prescription and over-the counter concomitant medications (including vitamins / herbs / supplements) since the previous study visit.

[0186] 3. Assess and record any additions, changes and / or deletions in skincare products used on the left and right axilla and / or inguinal area since the previous study visit.

[0187] 4. Assess for any new adverse events / adverse device effects (AEs / ADEs) or changes to previously recorded AEs / ADEs.

[0188] 5. Record date of last menstrual cycle for WOCBP.

[0189] 6. Remind subjects of after-treatment care instructions.

[0190] The following procedures will be performed at the 12- and 24-weeks post final treatment follow-up visits only:

[0191] 7. Cleanse subject’s treatment area with a mild cleanser.

[0192] 8. Trained staff will take standardized digital photographs of the subject’s left and right axilla and / or inguinal area.

[0193] 9. The Investigator (or qualified designee) will assess the left and right axilla and / or inguinal area.

[0194] 10. Subject will complete and return the Follow-Up Subject Questionnaire.

[0195] 11. A 4 mm punch biopsy may be obtained from the treatment area on either week 12 or week 24 post final treatment.

[0196] The 4-week post treatment follow-up visit will occur via phone unless it is determined by the Investigator or designated study staff that it is in the best interest of the subject to conduct the 4-week follow-up visit on-site or it is more convenient for both the subject and study staff to conduct the visit on-site. If the 4-week post treatment follow-up visit occurs on-site, photographs may be taken.

[0197] Example 9:

[0198] Inclusion and Exclusion Criteria

[0199] Inclusion Criteria. The subjects must meet all of the following inclusion criteria as listed in Table 5 to be included in the study.

[0200] Table 5: Inclusion Criteria.0201] Exclusion Criteria. The subjects will be excluded from the study if they meet any of the following exclusion criteria as listed in Table 6.

[0202] Table 6: Exclusion Criteria.

[0203] Example 10:

[0204] FIG. 4 shows photographs of patients affected with HS. FIG. 4A and FIG. 4B are photographs of arm pits showing the inflammation of a patient affected with HS. FIG. 4C is a photograph of area between the breasts showing the inflammation of a patient affected with HS. This is a chronic inflammatory skin condition characterized by recurrent deep-seated nodules and abscesses that rupture, leading to formation of sinus tracts & fibrotic scars. This is most commonly seen in areas rich with apocrine glands (e.g., axilla, groin). This condition causes pain and the skin lesions have drainage, odor, and scarring, which can lead to and cause negative social impact. HS is challenging to treat and often has taken on an un-effective multidisciplinary approach, including:

[0205] Early stages: Topical clindamycin, intralesional corticosteroid injections, topical resorcinol, certain systemic antibiotics, anti-androgen therapy, Acitretin, systemic corticosteroids, partial de-roofing.

[0206] Later stages: Wide excision surgery, immune suppressing biologies.

[0207] Example 11 :

[0208] Procedures for treatment of HS

[0209] Patients receive up to four (4) 1726 nm laser treatments up to 5 weeks apart. Multiple areas that have disease involvement may be treated. An initial energy of 20 J / cm2will be used to treat the entire area(s) (either axilla, inguinal, infra-mammary, thighs, or buttocks area), with the treater having the discretion to adjust the energy level (either increase or decrease) based on treatment outcomes and patienttolerability. For example, during a first treatment, the fluence may be increased to 22 J / cm2to 30 J / cm2. The second - fifth treatments may also be from fluences from 18 J / cm2to 30 J / cm2.

[0210] Example 12:

[0211] Demographics: 6 patients treated (Fitz II, V, VI with Mild HS treated on the Groin, Inframammary region or thigh)

[0212] Treatment:

[0213] Disposition: N=2 completed 3 treatments; N=4 completed 1 treatment

[0214] Settings: 20 J / cm2& 22 J / cm2.

[0215] Methodology: 1stpass to whole region, 2ndpass to specific lesions as applicable.

[0216] Efficacy: FIG. 5A and FIG. 5B shows early visible improvement in lesions on right groin treated when compared to untreated eft groin control side: 4 weeks post Tx 1 : N=1 (chronic draining from one nodule on treated side resolved); N=1 (lesion resolved on treated side; developed new lesion on untreated site).

[0217] Quality of Life (QOL) Questionnaire: Seeing decrease in “bother” by Tx 2. As used herein, bother is of pain, itch, drainage and / or odor of the lesions.

[0218] Safety / Discomfort: Treatments well tolerated with no serious or unexpected ADEs.

[0219] N=1 flare post Tx 2 (could have been triggered by stress).

[0220] FIG. 5A shows the results from one patient. FIG. 5A shows basline of right groin and the same spot two months after baseline and after two treatments. FIG. 5B shows the left goin (untreated control) from the same patient at the same timepoints. In FIG. 5A there is visible improvement in the lesions after the two treatments and in FIG. 5B there is visible worsening of the lesions. FIG. 5C shows the legend for lesion tracking.

Claims

CLAIMSWhat is claimed is:1 . A method of treating Hidradenitis Suppurativa (HS) in a patient comprising: irradiating a HS nodule with a spot or spots of a therapeutic laser pulse having a wavelength of about 1726 nm, and wherein the treatment resulted in improvement in the HS nodule as compared to baseline prior to treatment.

2. The method of claim 1 , wherein the patient is diagnosed with Hurley Scale Stage 1 HS or Hurley Scale Stage 2 HS.

3. The method of claim 1 , wherein the patient is diagnosed with HS on one or more of axilla, inguinal, groin, anogenital region, the areola or nipple of the female breast, the eyelids (Moll's glands), the external auditory canal, skin of the scalp and the face, or in areas where the skin rubs together, such as the armpits, groin, buttocks and breast areas.

4. The method of claim 1 , wherein the patient is diagnosed with HS in an area rich with apocrine glands, in an area with hair follicle blockage, or in areas with apocrine glands in a friction zone of the body.

5. The method of claim 4, wherein the area rich with apocrine glands is the axilla or groin, anogenital region, the areola and nipple of the female breast, the eyelids (Moll's glands), and the external auditory canal, and skin of the scalp and the face, and in areas where the skin rubs together, such as the armpits, groin, buttocks, breasts, and waistband area, back of the neck, behind the ears, and around the nape of the neck.

6. The method of claim 1 , wherein the patient is treated at least one time and up to five times.

7. The method of claim 1 , wherein the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline,wherein there is an improvement over basline after the first and / or second treatment..

8. The method of claim 7, wherein one measure of the HiSCR is a measure of the baseline total abscess and inflammatory nodule count (AN count).

9. The method of claim 7, wherein the patient has a one grade improvement on the HiSCR scale after being treated; or wherein the patient has a two grade improvement on the HiSCR scale after being treated.

10. The method of claim 7, wherein the patient has a 50% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

11. The method of claim 7, wherein the patient has a 25% reduction in total abscess and inflammatory nodule count (AN count) from baseline.

12. The method of claim 7, wherein the patient has no increase in nodule or abscess count after the treatment.

13. The method of claim 1 , wherein the patient is evaluated for pain level during the treatment using the 11 -point (0-10) Visual Analog Pain Scale.

14. The method of claim 1 , wherein the patient is evaluated for change in lesion count compared to baseline.

15. The method of claim 14, wherein the lesion count includes abscesses, nodules and tunnels.

16. The method of claim 1 , wherein the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline.

17. The method of claim 1 , wherein the patient is evaluated for change in Hurley Stage compared to baseline.

18. The method of claim 11 , wherein the Hurley Stage is Stage 1 , Stage 2 or Stage 3.

19. The method of claim 1 , wherein the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 4 weeks after final treatment.

20. The method of claim 1 , wherein the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 12 weeks after final treatment.

21. The method of claim 1 , wherein the patient is evaluated for change in Hidradenitis Suppurativa Clinical Response Scale (HiSCR) compared to baseline at about 24 weeks after final treatment.

22. The method of claim 1 , wherein the patient is evaluated for change in lesion count compared to baseline at about 4 weeks, about 12 weeks or about 24 weeks after final treatment.

23. The method of claim 1 , wherein the wavelength is from about 1710 nm to about 1735 nm.

24. The method of claim 1 , wherein the wavelength is from about 1720 nm to about 1730 nm.

25. The method of claim 1 , wherein the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 4 weeks after final treatment, wherein the final treatment can be the first, second, third, fourth or fifth treatment.

26. The method of claim 1 , wherein the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 12 weeks after final treatment.

27. The method of claim 1 , wherein the patient is evaluated for change in International Hidradenitis Suppurativa Severity Score System (IHS4) score compared to baseline at about 24 weeks after final treatment.

28. The method of claim 1 , wherein the patient is evaluated for change in Hurley Stage compared to baseline at about 4 weeks after final treatment.

29. The method of claim 1 , wherein the patient is evaluated for change in Hurley Stage compared to baseline at about 12 weeks after final treatment.

30. The method of claim 1 , wherein the patient is evaluated for change in Hurley Stage compared to baseline at about 24 weeks after final treatment.

31. The method of claim 1 , wherein the treatment applies to Fitzpatrick skin types l-VI.

32. The method of claim 1 , wherein the patient is at least 12 years of age or older.

33. The method of claim 1 , wherein the patient is aged between 12 and 80 years.

34. The method of claim 1 , wherein the patient has improvement in or full resolution in one or more of pain, itching, drainage or odor.

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