Oral sebetralstat for the treatment of an attack of hereditary angioedema

Abstract

The present invention relates to treatments of hereditary angioedema (HAE). In particular, the present invention provides on-demand treatments of hereditary angioedema (HAE) by orally administering a plasma kallikrein inhibitor sebetralstat to a patient in need thereof on-demand.

Description

[0001]TREATMENTS OF HEREDITARY ANGIOEDEMA The present invention relates to treatments of hereditary angioedema (HAE). In particular, the present invention provides on-demand treatments of hereditary angioedema (HAE) by orally administering a plasma kallikrein inhibitor to a patient in need thereof on-demand. Background to the invention Inhibitors of plasma kallikrein have a number of therapeutic applications, particularly in the treatment of hereditary angioedema.Plasma kallikrein (PKa) is a trypsin-like serine protease that can liberate kinins from kininogens (see K. D.Bhoola et al., "Kallikrein-Kinin Cascade", Encyclopedia of Respiratory Medicine, p483-493; J. W. Bryant et al., "Human plasma kallikrein-kinin system: physiological and biochemical parameters" Cardiovascular and haematological agents in medicinal chemistry, 7, p234-250, 2009; K. D. Bhoola et al., Pharmacological Rev., 1992, 44, 1; and D. J. Campbell, "Towards understanding the kallikrein-kinin system: insights fromthe measurement of kinin peptides", Brazilian Journal of Medical and Biological Research 2000, 33,665-677). Plasma prekallikrein is encoded by a single gene and is mainly synthesized in the liver, as well as other tissues. It is secreted by hepatocytes as a zymogen that circulates in plasma as a heterodimer complex bound to high molecular weight kininogen (HK) which is activated to give the active PKa.Factor XIIa (FXIIa) mediates conversion of plasma prekallikrein to PKa, which is a serine protease thatcleaves high molecular weight kininogen (HK) to generate bradykinin, a potent inflammatory hormone.Kinins are potent mediators of inflammation that act through G protein-coupled receptors and antagonists of kinins (such as bradykinin receptor antagonists) have previously been investigated as potential therapeutic agents for the treatment of a number of disorders (F. Marceau and D. Regoli, Nature Rev., Drug Discovery, 2004, 3, 845-852). Activation of the kallikrein-kinin system (KKS) is initiated by a variety of physiological (e.g. negatively charged surfaces) and pathological factors, which induce a conformational change in FXII leading to itscleavage and activation by certain proteases e.g. plasmin (Hofman et al Clin Rev Allergy Immunol 2016),which may not require negative surfaces, or by misfolded proteins (Maas et al J Clinical Invest 2008). Activation of plasma prekallikrein to PKa by FXIIa is followed by reciprocal activation of FXII to FXIIa by PKa and thereby provides positive feedback amplification of the KKS. The biologically active peptide bradykinin activates bradykinin 2 receptors (B2R) that are expressed on a variety of vascular, neuronal, and immune cell types (Kaplan AP, Joseph K. Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway. Adv Immunol. 2014;121:41-89). The interaction between bradykinin and B2R activates proinflammatory signalling pathways that mediate, for example, angioedema, pain, inflammation, chemotaxis of neutrophils, vascular hyperpermeability, and vasodilatation (see Kaplan et al., Adv Immunol. 2014;121:41-89; and Hopp et al., J Neuroinflammation.2017 Feb 20;14(1):39).PKa is thought to play a role in a number of inflammatory disorders. The major inhibitor of PKa is theserpin C1 esterase inhibitor (C1INH). People with a genetic deficiency in C1INH levels or function due tomutation in SERPING1 can develop hereditary angioedema (HAE-C1INH) which can result in intermittentswelling of face, extremities, larynx, gastro-intestinal tract and genitals. Plasma from HAE patients haveincreased levels of cleaved HK, which indicates the generation of bradykinin (PLoS ONE 8(8): e74043.2013). Treatment with PKa inhibitors, (such as the approved medicinal products ecallantide, lanadelumab,and berotralstat) has been shown to effectively treat HAE- C1INH.Hereditary angioedema (HAE) is a rare inherited disorder characterised by recurrent acute attacks where fluids accumulate outside of the blood vessels, blocking the normal flow of blood or lymphatic fluid and causing rapid swelling of tissues such as in the hands, feet, limbs, face, intestinal tract, or airway. “Hereditary angioedema” can thus be defined as any disorder characterised by recurrent episodes of bradykinin-mediated angioedema (e.g. severe swelling) caused by an inheriteddysfunction / fault / mutation. There are currently three known categories of HAE: (i) HAE type 1, (ii) HAEtype 2, and (iii) HAE with normal C1INH levels and function (HAE-nC1INH). However, the HAE field isdeveloping quickly so it is expected that further types of HAE might be defined in the future. Without wishing to be bound by theory, it is thought that HAE type 1 is caused by mutations in theSERPING1 gene that lead to reduced levels of C1INH in in the blood. Without wishing to be bound bytheory, it is thought that HAE type 2 is caused by mutations in the SERPING1 gene that lead to dysfunctionof the C1INH in the blood.Unlike HAE types 1 and 2 (also called HAE-C1INH), the pathophysiology of HAE-nC1INH is heterogeneousand not fully understood. Without wishing to be bound by theory, the cause of HAE-nC1INH is lesswell-defined and the underlying genetic dysfunction / fault / mutation can sometimes remain unknown.What is known is that the cause of HAE-nC1INH is not related to reduced levels or dysfunction of theC1INH (in contrast to HAE types 1 and 2). Currently, there are difficulties in diagnosing patients with HAE-nC1INH. Indeed, the absence of universally accepted criteria for the diagnosis of HAE-nC1INH limits estimates of its prevalence. At present, HAE-nC1INH can be diagnosed by reviewing the family history and noting that angioedema hasbeen inherited from a previous generation (and thus it is hereditary angioedema). HAE-nC1INH can alsobe diagnosed by determining that there is a dysfunction / fault / mutation in a gene other than those related to C1INH. For example, it has been reported that dysfunction / fault / mutation with plasminogen can causeHAE-nC1INH (see e.g. Veronez et al., Front Med (Lausanne).2019 Feb 21;6:28; or Recke et al., Clin TranslAllergy.2019 Feb 14;9:9.). It has also been reported that dysfunction / fault / mutation with F12 gene andFactor XII can cause HAE-nC1INH (see e.g. Mansi et al., 2014 The Association for the Publication of theJournal of Internal Medicine Journal of Internal Medicine, 2015, 277; 585–593; or Maat et al. J ThrombHaemost. 2019 Jan;17(1):183-194). However, the genetic cause in most patients with HAE-nC1INH isunknown, and this subtype is referred as HAE-UNK or AE-UNK (Bork K et al. Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations. Allergy.2015 Aug;70(8):1004-12, Bork K et al. Gene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor. J Allergy Clin Immunol Pract.2023 Aug;11(8):2441-2449). About 87% of patients diagnosed with HAE-nC1INH have an unknown mutation, limiting the utility of genetic tests to establish the diagnosis.Acute HAE attacks (shortened to “HAE attacks”) normally progress through three key clinically distinctstages: an initial prodromal stage (that can typically last for up to 12 hours), followed by a swelling stage, and then an absorption stage. A majority of HAE attacks announce themselves with prodromal symptoms. Two thirds of prodromes appeared less than 6 hours before a HAE attack and no prodromes occur more than 24 hours before a HAE attack (Magerl et al., Clinical and Experimental Dermatology 2014, 39, 298-303). For example, the following prodromal symptoms may start to be observed: a slight swelling (particularly affecting the face and neck), a typical type of abdominal pain, a typical reddening of the skin called "erythema marginatum". An attack is fully developed when it has reached maximum swelling and maximum expression of pain (e.g. abdominal attack), discomfort (e.g. peripheral attack) or threat to life (e.g. laryngeal attack). Once the attack has reached its peak, the subsequent time period to normalization is determined by the time it takes for the swelling to disappear and the liquid that has penetrated the tissues to be reabsorbed. Synthetic and small molecule plasma kallikrein inhibitors have been described previously, for example byGarrett et al. ("Peptide aldehyde…." J. Peptide Res.52, 62-71 (1998)), T. Griesbacher et al. ("Involvementof tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenouskinins in acute pancreatitis in rats" British Journal of Pharmacology 137, 692-700 (2002)), Evans ("Selectivedipeptide inhibitors of kallikrein" WO03 / 076458), Szelke et al. ("Kininogenase inhibitors" WO92 / 04371),D. M. Evans et al. (Immunolpharmacology, 32, p115-116 (1996)), Szelke et al. ("Kininogen inhibitors"WO95 / 07921), Antonsson et al. ("New peptides derivatives" WO94 / 29335), J. Corte et al. (”Six memberedheterocycles useful as serine protease inhibitors” WO2005 / 123680), J. Stürzbecher et al. (Brazilian J. Med.Biol. Res 27, p1929-34 (1994)), Kettner et al. (US 5,187,157), N. Teno et al. (Chem. Pharm. Bull.41, p1079-1090 (1993)), W. B. Young et al. ("Small molecule inhibitors of plasma kallikrein" Bioorg. Med. Chem. Letts.16, p2034-2036 (2006)), Okada et al. ("Development of potent and selective plasmin and plasma kallikreininhibitors and studies on the structure-activity relationship" Chem. Pharm. Bull. 48, p1964-72 (2000)),Steinmetzer et al. ("Trypsin-like serine protease inhibitors and their preparation and use" WO08 / 049595),Zhang et al. ("Discovery of highly potent small molecule kallikrein inhibitors" Medicinal Chemistry 2, p545-553 (2006)), Sinha et al. ("Inhibitors of plasma kallikrein" WO08 / 016883), Shigenaga et al. (“PlasmaKallikrein Inhibitors” WO2011 / 118672), and Kolte et al. (“Biochemical characterization of a novel high-affinity and specific kallikrein inhibitor”, British Journal of Pharmacology (2011), 162(7), 1639-1649). Also, Steinmetzer et al. (“Serine protease inhibitors” WO2012 / 004678) describes cyclized peptide analogs which are inhibitors of human plasmin and plasma kallikrein. As explained above, HAE can manifest in patients who present with a genetic deficiency or dysfunction in C1 esterase inhibitor. Thus, some of the current treatments of HAE involve administering a C1 esterase inhibitor to normalise the deficiency or dysfunction in C1 esterase inhibitor. Such treatments can beprophylactic (i.e. administered in the absence of acute HAE attack symptoms to prevent / reduce thelikelihood of an acute HAE attack) and / or acute treatments (i.e. administered when acute HAE attacksymptoms are noticed to try to stop or reduce the severity of the acute HAE attack). Cinryze® and Haegarda® contain a C1 esterase inhibitor and are authorised to prevent acute HAE attacks (i.e. prophylactic treatment). Treatment with Cinryze® requires the preparation of a solution from a powder, which is then injected every 3 or 4 days. Similarly, treatment with Haegarda® requires the preparation of a solution from a powder, which is then injected twice a week. It is not always possible for a patient to self-administer these treatments, and if this is the case, the patient is required to visit a clinic for treatment. Thus, both of these prophylactic treatments suffer from high patient burden. Additionally, the FDA packet insert for Haegarda® states that it “should not be used to treat an acute HAE attack”, and therefore a patient may require additional therapy if a HAE attack develops. Berinert® and Ruconest® contain a C1 esterase inhibitor and are authorised to treat acute HAE attacks. Both of these treatments also involve the preparation of an injectable solution followed by injection. This process can be burdensome on the patient, especially when the patient is suffering from an acute HAE attack. Self-administration of the dosage amount is also not always possible, and if it is not, administration of the drug can be substantially delayed thus increasing the severity of the acute HAE attack for the patient. Kalbitor® (active substance ecallantide) and Takhzyro® (active substance lanadelumab) are selective plasma kallikrein inhibitors approved for medical use in the treatment of HAE. Both treatments are formulated as solutions for injection. Ecallantide is a large protein plasma kallikrein inhibitor that presentsa risk of anaphylactic reactions. Indeed, the EU marketing authorisation application for Kalbitor® hasrecently been withdrawn because the benefits of Kalbitor® are said to not outweigh its risks. Lanadelumab is a recombinant fully human IgG1 kappa light chain monoclonal antibody. Reported adverse reactions of treatment with lanadelumab include hypersensitivity, injection site pain, injection site erythema, and injection site bruising. The authorised EMA label for Takhzyro® (active substance lanadelumab) states thatit “is not intended for treatment of acute HAE attacks” and that “in case of a breakthrough HAE attack,individualized treatment should be initiated with an approved rescue medication”. Also, as injections, both of these treatments involve a high patient burden. Berotralstat (BCX7353) has been approved in some countries for preventative treatment of HAE (not as an on-demand treatment), e.g. under the brand name Orladeyo®. Hwang et al. (Immunotherapy (2019) 11(17), 1439–1444) states that higher doses were associated with more gastrointestinal adverse effects indicating increased toxicity at higher levels. Furthermore, many molecules in the known art feature a highly polar and ionisable guanidine or amidine functionality. It is well known that such functionalities may be limiting to gut permeability and therefore to oral availability. For example, it has been reported by Tamie J. Chilcote and Sukanto Sinha (“ASP-634:An Oral Drug Candidate for Diabetic MacularEdema”, ARVO 2012 May 6th – May 9th, 2012, FortLauderdale, Florida, Presentation 2240) that ASP-440, a benzamidine, suffers from poor oral availability. It is further reported that absorption may be improved by creating a prodrug such as ASP-634. However, it is well known that prodrugs can suffer from several drawbacks, for example, poor chemical stability and potential toxicity from the inert carrier or from unexpected metabolites. In another report, indole amides are claimed as compounds that might overcome problems associated with drugs possessing poor or inadequate ADME-tox and physicochemical properties although no inhibition against plasma kallikrein is presented or claimed (Griffioen et al., “Indole amide derivatives and related compounds for use in the treatment of neurodegenerative diseases”, WO2010142801). Other plasma kallikrein inhibitors known in the art are generally small molecules, some of which include highly polar and ionisable functional groups, such as guanidines or amidines. Recently, plasma kallikrein inhibitors that do not feature guanidine or amidine functionalities have been reported. For exampleBrandl et al. (“N-((6-amino-pyridin-3-yl)methyl)-heteroaryl-carboxamides as inhibitors of plasmakallikrein” WO2012 / 017020), Evans et al. (“Benzylamine derivatives as inhibitors of plasma kallikrein”WO2013 / 005045), Allan et al. (“Benzylamine derivatives” WO2014 / 108679), Davie et al. (“Heterocyclicderivates” WO2014 / 188211), Davie et al. (“N-((het)arylmethyl)-heteroaryl-carboxamides compounds asplasma kallikrein inhibitors” WO2016 / 083820). The applicant has developed a novel series of compounds that are inhibitors of plasma kallikrein, which are disclosed in WO2016 / 083820 (PCT / GB2015 / 053615). These compounds demonstrate good selectivity for plasma kallikrein. One such compound is N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3- (methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide. The name N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1- yl)methyl]phenyl}methyl)pyrazole-4-carboxamide denotes the structure depicted below, which is known by its codename “KVD900”. The INN for KVD900 is sebetralstat, which is how this compound will be described throughout this application. Sebetralstat. Certain dosage forms comprising sebetralstat are disclosed in Collett et al. WO2019 / 106361. Orodispersible tablets comprising sebetralstat are disclosed in WO2023 / 209381. Treatments of HAE comprising sebetralstat are discussed in WO2020 / 249977 and WO2022 / 084693.Sebetralstat met all of its phase 2 efficacy and safety endpoints (see clinical trial NCT04208412). Theresults of this phase 2 study are discussed in WO2022 / 172006. To date, there is a lack of approved oral treatments for HAE (see e.g. Craig et al. Int Arch Allergy Immunol. 2014;165(2):119-27. doi: 10.1159 / 000368404; Mager et al., Immunol Allergy Clin North Am. 2017 Aug;37(3):571-584). There are no approved oral on-demand treatments for HAE. Instead, the majority of available treatments are injectables. Injectables suffer from many disadvantages compared to oral treatments, largely relating to patient compliance. For example, injectables are more inconvenient than oral treatments e.g. needing to be in a suitable environment to formulate and then administer the injection, and also causing pain at the injection site. Reduced patient compliance can lead to patients delaying treatment, which generally leads to attack symptoms getting worse, or even avoiding treatment altogether. Indeed, many patients suffering from HAE simply hope that any attack will dissipate on its own to avoid administering an injection. Injectable treatments suffer from late dosing because the patient may need to prepare the dosage form or even travel to hospital for treatment. Therefore, HAE treatment is often undermined by late dosing caused by the high burden on the patient. Indeed, Maurer M et al. (PLoS ONE 2013;8(2): e53773. doi:10.1371 / journal.pone.0053773) explains that more than 60% of patients administer their HAE injectable more than one hour after the onset of an attack. Icatibant (marketed as Firazyr®) is the predominant on-demand treatment for HAE, and is administered by subcutaneous injection. In a real-world study of HAE patients with access to icatibant (Maurer M et al. PLoS ONE 2013;8(2): e53773. doi:10.1371 / journal.pone.0053773), less than 40% of treated attacks were dosed within an hour of onset, with 30% not being treated until over 5 hours after onset. Further, 45% of attacks in this study were not treated at all. Therefore, there is an unmet need to provide patients with improved treatment options to treat HAE attacks on-demand. HAE attacks resolve faster and are shorter after early treatment (Maurer M et al. PLoS ONE 2013;8(2): e53773. doi:10.1371 / journal.pone.0053773) and thus early intervention when an attack is expected, or ongoing, is essential to desirably manage the disease. Nevertheless, there is currently a reliance oninjectable therapies for on-demand treatment of HAE patients, and further patient confidence that oralon-demand therapies can replace injectable therapies would be desirable. Patients must have confidencein any alternative (non-injectable) therapy if they are to move away from their current therapy to such alternative therapies. Definitions The terms “attack of HAE”, “HAE attack”, and “attack”, etc. are used interchangeably herein. The term “hereditary angioedema” (shortened to HAE) means any bradykinin-mediated angioedema caused by an inherited genetic dysfunction, fault, or mutation. As a result, the term “HAE” includes at least HAE type 1, HAE type 2, and HAE with normal C1INH levels and function (HAE-nC1INH). Sebetralstat used in the present invention can also be in the preferred crystalline form (Form 1), which exhibits at least the following characteristic X-ray powder diffraction peaks (Cu Kα radiation, expressed in degrees 2θ) at approximately: (1) 11.2, 12.5, 13.2, 14.5 and 16.3; or (2) 11.2, 12.5, 13.2, 14.5, 16.3, 17.4 and 17.9; or (3) 11.2, 12.5, 13.2, 14.5, 16.3, 17.4, 17.9, 21.2 and 22.0. The term "approximately" means in this context that there is an uncertainty in the measurements of the degrees 2θ of ± 0.3 (expressed in degrees 2θ), preferably ± 0.2 (expressed in degrees 2θ). Form 1 can also have an X ray powder diffraction pattern comprising characteristic peaks (expressed in degrees 2θ) at approximately 4.4, 11.2, 12.5, 13.2, 14.5, 16.3, 17.4, 17.9, 21.2, 22.0 and 22.6. Form 1 can also have an X-ray powder diffraction pattern substantially the same as that shown in Figure 1. In any of the treatments of the invention described herein, the term “sebetralstat” is shorthand for “sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof)”. It will be understood that “pharmaceutically acceptable salts and / or solvates thereof” means “pharmaceutically acceptable salts thereof”, “pharmaceutically acceptable solvates thereof”, and “pharmaceutically acceptable solvates of salts thereof”. The preferred form of sebetralstat is the free base form, specifically the anhydrous free base form (when it is possible to keep the free base anhydrous). The term "pharmaceutically acceptable salt" means a physiologically or toxicologically tolerable salt, which can be, for example, pharmaceutically acceptable acid addition salts. For instance, as sebetralstat contains a basic group, e.g. a basic nitrogen, pharmaceutically acceptable acid addition salts that can be formed include hydrochlorides, hydrobromides, sulfates, phosphates, acetates, citrates, lactates, tartrates, mesylates, succinates, oxalates, phosphates, esylates, tosylates, benzenesulfonates, naphthalenedisulphonates, maleates, adipates, fumarates, hippurates, camphorates, xinafoates, pacetamidobenzoates, dihydroxybenzoates, hydroxynaphthoates, succinates, ascorbates, oleates, bisulfates and the like. The preferred pharmaceutically acceptable salt of the compound is the hydrochloride salt. Hemisalts of acids can also be formed, for example, hemisulfate salts. For a review of suitable salts, see "Handbook of Pharmaceutical Salts: Properties, Selection and Use" by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). The term “solvate” is used herein to describe a molecular complex comprising sebetralstat and a one or more pharmaceutically acceptable solvent molecules, for example, ethanol or water. The term “hydrate”is employed when the solvent is water and for the avoidance of any doubt, the term “hydrate” isencompassed by the term “solvate”. “Sebetralstat” may include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds wherein hydrogen is replaced by deuterium or tritium, or wherein carbon is replaced by13C or14C, are within the scope of the present invention.“On-demand” treatment, in the context of HAE, means that sebetralstat is administered upon need oftherapy in connection with one specific HAE attack. “On-demand” does not require the administration ofsebetralstat continuously at regular intervals (e.g. once a week, twice a week, etc.) irrespective of aninstance of an HAE attack. This is in contrast to some other known treatments of HAE (e.g. treatments with Cinryze® and Haegarda®, as described above) that require continuous and regular dosing for therapy.Instead, in treatments of the invention, sebetralstat is taken when the patient requires fast-actingtherapeutic effects. These are discussed below in more detail. In any of the treatments of the invention described herein, the patient is preferably a human. HAE can affect patients of all ages. Accordingly, the human patient can be a child (ages 0 to less than 18 years) or an adult (18 years old or older). In any of the treatments described herein, the patient can have a predisposition to angioedema. Specifically, the patient can be aged 12 years and above. The patient can also be aged 2 years and above. The human patient can be aged between 2 and less than 18. The human patient can be aged between 2 and less than 12. The human patient can be aged between 12 and less than 18. The patient can be at least 70 years old. As used herein, the “second treatment of the HAE attack” or “second treatment” is the administration of any dose of active pharmaceutical ingredient for treating an HAE attack on-demand that is not sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The second treatment can be an existing HAE treatment. For example, the “second treatment” can be pdC1INH, rhC1INH, icatibant, conestat alfa (Ruconest®), or ecallantide. For the avoidance of any doubt, “second treatment of an HAE attack” does not include prophylactic treatments of HAE. As used herein, the terms “second dose”, “third dose”, “fourth dose” and “further dose” refer to the administration of a dose of sebetralstat subsequent to the initial dose. “To resolve the attack” or “attack resolution”, unless specified otherwise, means that the HAE attackclears without the need for a further dose of sebetralstat or a second treatment.The term “consecutive time points” when used in the context of “symptom relief” can mean anassessment separated by 30 mins (particularly within 0-4 hours after administration of the compound).“Consecutive time points” can also mean an assessment separated by 1 hour (particularly within 4-12 hours after administration of the compound). “Consecutive time points” can also mean an assessmentseparated by 3 hours (particularly within 12-24 hours after administration of the compound).As used herein, the term “orodispersible tablet” (ODT) means a tablet that is intended to be placed directly in the mouth where they rapidly disintegrate in saliva before they are swallowed. An ODT is not a swallowable tablet, for instance a conventional swallowable tablet or capsule. Description of the inventionThe efficacy data from the phase 3 study described in Example 4 confirm that treatment with sebetralstatreduces the time to beginning of symptom relief, reduces the time to a reduction in attack severity andachieves complete attack resolution. These results are statistically significant.More specifically, the efficacy data from the phase 3 study described in Example 4 report that sebetralstattreatment can be used across a wide range of attack locations and severities, including severe and very severe attacks, and including attacks of the neck and above, which can be life-threating types of attack. Further, the data described herein report that sebetralstat (a plasma kallikrein inhibitor) is effective inpatients who are also being treated with a prophylactic HAE treatment (even when the prophylactictreatment is also a plasma kallikrein inhibitor). More specifically, the data described herein show thatsebetralstat (a plasma kallikrein inhibitor) can be used on-demand to treat HAE attacks in patients whoare also being treated with a prophylactic HAE treatment (even when the prophylactic treatment is alsoa plasma kallikrein inhibitor), even if the HAE attack is a severe or very severe attack and / or where theHAE attack is an attack of the neck and above but is not a laryngeal attack. The attack of the neck andabove can be a facial attack (i.e., an attack of the face) and / or an attack of the tongue and / or an attack ofthe throat.The phase 3 results report that sebetralstat provided rapid symptom relief in a broad HAE population thatreflects clinical practice, and was safe and well-tolerated with a safety profile comparable with placebo. These results can provide patients with further confidence that they are able to treat a wide range of HAE attacks, including the most extreme attacks. Treatment of severe or worse HAE attacks As noted above, HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of unpredictable and often debilitating swelling in various parts of the body, including the hands, feet, genitals, stomach, face and / or throat. Severe attacks can be life-threatening and therefore it is ofparamount importance that any on-demand treatment is fast-acting and effective.Further, current on-demand treatments involve high patient burden such that patients do not treat early enough and often delay treatment with injectables in the hope that the HAE attack will dissipate on its own, which leads to delayed (or even no) treatment. This can lead to more severe attacks, longer recovery time and the need for more serious medical intervention. There is therefore a particular need for an effective treatment of severe and very severe attacks, which is a problem addressed by the present invention. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is a severe or worse HAEattack. In particular, the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterisedas “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as“severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. PGI-S is a known scale in the art (see e.g. Allergy Asthma Proc. 2018 Jan 1;39(1):74-80. Doi: 10.2500 / aap.2018.39.4095) that can be used to report the severity of HAE attacks and for example can be used to report attacks as “none”, “mild”, “moderate”, “severe” or “very severe”. Where appropriate, any of the treatments described herein can be for treating an HAE attack that is characterised as “severe” or above according to the PGI-S scale. Specific embodiments are as follows.Specific treatments of severe or worse HAE attacksThe invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. In an embodiment, the first dose is administered on-demand within 1 hour of recognition of a symptom of an acute HAE attack. In another embodiment, the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, or within about 5minutes of the symptom of an acute HAE attack being recognised. In an embodiment, a second dose isnot administered to the patient, e.g., where the first dose provides sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a second dose to the patient. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In an embodiment, the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose. Preferably, the second dose is administered about 3 hours after the first dose. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose. In an embodiment, a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a third dose to the patient. In an alternative embodiment, the patient is administered a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof).The third dose can be administered between about 2 hours and about 6 hours (more specifically, betweenabout 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about3 hours) after the second dose. Preferably, the third dose can be administered about 3 hours after thesecond dose. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof),wherein the second dose is administered between about 2 hours and about 6 hours after the first dose,preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose. In an embodiment, a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a fourth dose to the patient. In an alternative embodiment, the patient is administered a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose. Preferably, the fourth dose can be administered about 3 hours after the third dose. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof)followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof). The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof)followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose. In an embodiment, no further dose is administered to the patient, e.g., the attack is resolved without administering any further dose to the patient, in particular, no fifth dose is administered.In any of the above embodiments, each dose is preferably administered as two unit doses. In particular,each unit dose is preferably administered as two tablets (e.g. a film-coated tablet or an orodispersibletablet) each comprising about 300mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactictreatment of HAE. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-Sscale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent. The prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor. The prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist. The prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor. The prophylactic treatment of HAE can be attenuated androgen. In particular, the attenuated androgen can be danazol or oxandrolone. The prophylactic treatment of HAE can be tranexamic acid. Alternatively, the prophylactic treatment of HAE can be non-androgen therapy. The prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The prophylactic treatment of HAE can be C1 inhibitor. In particular, the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®. The prophylactic treatment can be lanadelumab or berotralstat. The prophylactic treatment can be lanadelumab. The prophylactic treatment can be berotralstat. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactictreatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. In an embodiment,the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, orHaegarda®), donidalorsen, and deucrictibant. In an embodiment, the HAE attack is characterised as“severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale and wherein the patient is also being treated with a prophylactictreatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. Inan embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactictreatment of HAE, wherein the prophylactic treatment is lanadelumab. In an embodiment, the HAE attackis characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactictreatment of HAE, wherein the prophylactic treatment is berotralstat. In an embodiment, the HAE attackis characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatmentof HAE and wherein the attack is resolved without administering a second dose to the patient. In anembodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatmentof HAE, wherein the prophylactic treatment is lanadelumab, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. Alternatively, the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is not also being treated with aprophylactic treatment of HAE. In an embodiment, the HAE attack is characterised as “severe” accordingto the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also beingtreated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected fromlanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also beingtreated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. Alternatively, the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is not also being treated with a prophylactic treatment of HAE. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. In any of the above embodiments, the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals. In an embodiment, the HAE attack is a laryngeal attack. In an embodiment, the HAE attack is an attack of the neck and above. In an embodiment, the HAE attack is an attack of the neck and above but is not a laryngeal attack. In an embodiment, the HAE attackis an abdominal attack. In an embodiment, the HAE attack is a subcutaneous attack. In an embodiment,the HAE attack is an attack of the arms. In an embodiment, the HAE attack is an attack of the hands. In anembodiment, the HAE attack is an attack of the legs. In an embodiment, the HAE attack is an attack of thefeet. In an embodiment, the HAE attack is an attack of the head. In an embodiment, the HAE attack is anattack of the face. In an embodiment, the HAE attack is an attack of the neck. In an embodiment, the HAEattack is an attack of the torso. In an embodiment, the HAE attack is an attack of the genitals.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale and wherein the HAE attack is a laryngeal attack. In an embodiment,the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAEattack is characterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “mild” orabove according to the PGI-S scale and wherein the HAE attack is a laryngeal attack. In an embodiment,the HAE attack is characterised as “mild” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “moderate”or above according to the PGI-S scale and wherein the HAE attack is a laryngeal attack. In an embodiment,the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” orabove according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attackis resolved without administering a second dose to the patient. In an embodiment, the HAE attack ischaracterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack ischaracterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “mild” orabove according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attackis resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “moderate”or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attackis resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an abdominal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a subcutaneous attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a laryngeal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attackis characterised as “severe” or above according to the PGI-S scale, wherein the HAE attack is a laryngealattack, and wherein the attack is resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attackis characterised as “mild” or above according to the PGI-S scale, wherein the HAE attack is a laryngealattack, and wherein the attack is resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attackis characterised as “moderate” or above according to the PGI-S scale, wherein the HAE attack is a laryngealattack, and wherein the attack is resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an abdominal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a subcutaneous attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack. For the avoidance of doubt, any of the embodiments described above in relation to the treatment of severe or worse HAE attacks according to the invention can, where appropriate, be considered incombination with any of the embodiments described below in relation to the treatment of HAE attacks inpatients on prophylactic treatment, dosing, the treatment of HAE attacks of the neck and above, specificcombination therapies and drug-drug interactions. It is intended that any of the embodiments can be combined. Treatment of HAE attacks in patients on prophylactic treatment As noted above, existing treatments of HAE are either administered on-demand or as a prophylactic.On-demand treatment is administered in response to a specific attack to lessen its severity e.g., at thefirst sign of attack symptoms. Prophylactic treatment involves continuously and regularly taking treatment to reduce the likelihood of an attack occurring i.e. not in response to one specific attack. The overarching goal of long-term prophylactic treatment is to achieve an attack-free status. However, existing prophylactic treatments are generally not completely effective, with patients receivingprophylactic treatment still suffering from HAE attacks. This is demonstrated by the attack incidences datataken from patients on prophylactic treatment that are reported in Example 4 and in Figures 2 and 3. Forthis reason, it is generally recommended that HAE patients carry an on-demand treatment at all times even if they are on prophylactic treatment (such treatment can sometimes be called a “rescuetreatment”). In fact, the approved labels for both Takhzyro® and Orladeyo® recommend that a patientcarry a rescue treatment in the case of an HAE attack. Patients on prophylactic treatment therefore still face the risk of having an attack and continue to experience burden in their day-to-day life, largely due to the challenges associated with current parenteral on-demand therapies, as described above.In particular, the location, duration and severity of attacks are similar between patients receivingprophylactic treatment and patients who are taking on-demand treatment only (see Figures 2 and 3,which shows the distribution of attack severity (PGI-S) at baseline in the Phase 3 clinical trial investigatingsebetralstat, the results of which are reported herein). Notably, patients on prophylactic treatment stillexperience severe and very severe attacks, regardless of the use of prophylaxis (see also Maurer M,Magerl M, Betschel S, et al. The international WAO / EAACI guideline for the management of hereditaryangioedema—The 2021 revision and update. Allergy. 2022; 77: 1961–1990. doi:10.1111 / all.15214). Accordingly, all HAE patients, regardless of their current treatment regime (or lack thereof) would benefit from having effective on-demand treatments of HAE, which is a need addressed by the present invention. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE. The invention provides sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) for use in treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE. The invention provides a prophylactic treatment of HAE for use in treating hereditary angioedema (HAE), wherein the patient is orally administered a first dose of 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) on-demand for treating an attack of HAE on-demand. The invention provides sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) and a prophylactic treatment of HAE for use in treating hereditary angioedema (HAE) in a patient in need thereof comprising: administering the prophylactic treatment of HAE to the patient and orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) for treating an attack of HAE on-demand. For the avoidance of doubt, any of the embodiments described above in relation to the treatment of severe or worse HAE attacks according to the invention, or below in relation to dosing, the treatment ofHAE attacks of the neck and above, specific combination therapies and drug-drug interactions can, whereappropriate, be considered in combination with any of embodiments described herein relation totreatment of HAE attacks in patients on prophylactic treatment. It is intended that any of theembodiments can be combined. Therefore, where appropriate, any of the treatments described herein can therefore be for treating an HAE attack wherein the patient is also being treated with a prophylactic treatment of HAE. Specific embodiments are as follows.Specific treatments of HAE attacks in patients on prophylactic treatmentIn any of the embodiments described herein, sebetralstat and the prophylactic treatment of HAE can be administered simultaneously, separately or sequentially. For the avoidance of doubt, sebetralstat and the prophylactic treatment of HAE are not necessarily given at the same time, i.e., sebetralstat and theprophylactic treatment of HAE can be given at different times of the day. Indeed, this would be expectedbecause a patient would typically take their prophylactic treatment at a particular time, whereas the on-demand treatment would be used as necessary upon recognition of a HAE attack.In any of the embodiments described herein, the first dose can be administered on-demand within 1 hourof recognition of a symptom of an acute HAE attack. In another embodiment, the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom ofan acute HAE attack being recognised. In an embodiment, a second dose is not administered to thepatient, e.g., where the first dose provides sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In an embodiment, the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose. Preferably, the second dose is administered about 3 hours after the first dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose. In an embodiment, a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved withoutadministering a third dose to the patient. In an alternative embodiment, the patient is administered athird dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The third dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the second dose. Preferably, the third dose can be administered about 3 hours after the second dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose. In an embodiment, a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack is resolved without administering a fourth dose to the patient. In an alternative embodiment, the patient is administered a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose. Preferably, the fourth dose can be administered about 3 hours after the third dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after thesecond dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours afterthe third dose, preferably about 3 hours after the third dose. In an embodiment, no further dose is administered to the patient, e.g., the attack is resolved without administering any further dose to the patient, in particular, no fifth dose is administered. In any of the above embodiments, each dose is preferably administered as two unit doses. In particular, each unit dose is preferably administered as two tablets (e.g. a film-coated tablet or an orodispersible tablet) each comprising about 300mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In any of the above embodiments, the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent. The prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor. The prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist. The prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor. The prophylactic treatment of HAE can be attenuated androgen. In particular, the attenuated androgen can be danazol or oxandrolone. The prophylactic treatment of HAE can be tranexamic acid. Alternatively, the prophylactic treatment of HAE can be non-androgen therapy. The prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The prophylactic treatment of HAE can be C1 inhibitor. In particular, the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®. The prophylactic treatment can be lanadelumab or berotralstat. The prophylactic treatment can be lanadelumab. The prophylactic treatment can be berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat,STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®),donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected fromgaradacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, orHaegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, anddeucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215,C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, orHaegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selectedfrom garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof)followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours afterthe first dose, preferably about 3 hours after the first dose, wherein the third dose is administeredbetween about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after thesecond dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours afterthe third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours afterthe first dose, preferably about 3 hours after the first dose, wherein the third dose is administeredbetween about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose, and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). In any of the above embodiments, the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals. In an embodiment, the HAE attack is a laryngeal attack. In an embodiment, the HAE attack is an attack of the neck and above. In an embodiment, the HAE attack is an attack of the neck and above but is not a laryngeal attack. In an embodiment, the HAE attackis an abdominal attack. In an embodiment, the HAE attack is a subcutaneous attack. In an embodiment,the HAE attack is an attack of the arms. In an embodiment, the HAE attack is an attack of the hands. In anembodiment, the HAE attack is an attack of the legs. In an embodiment, the HAE attack is an attack of thefeet. In an embodiment, the HAE attack is an attack of the head. In an embodiment, the HAE attack is anattack of the face. In an embodiment, the HAE attack is an attack of the neck. In an embodiment, the HAEattack is an attack of the torso. In an embodiment, the HAE attack is an attack of the genitals.The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a laryngeal attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a laryngeal attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the HAE attack is a laryngeal attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis lanadelumab and wherein the HAE attack is a laryngeal attack.The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein theHAE attack is a laryngeal attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with aprophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and wherein theattack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the attack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (suchas Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein the attack is resolved withoutadministering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, whereinthe patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis lanadelumab and wherein the attack is resolved without administering a second dose to the patient.The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, whereinthe patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis berotralstat and wherein the attack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, whereinthe patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein theattack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is asubcutaneous attack. In an embodiment, the prophylactic treatment is selected from lanadelumab,berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the HAE attack is a subcutaneous attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and wherein the HAE attack is a subcutaneous attack. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein theHAE attack is a subcutaneous attack. In any of the above embodiments, the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterisedas “mild” according to the PGI-S scale. In an embodiment, the prophylactic treatment is selected fromlanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis lanadelumab and the HAE attack is characterised as “mild” according to the PGI-S scale.The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and the HAE attackis characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterisedas “moderate” according to the PGI-S scale. In an embodiment, the prophylactic treatment is selectedfrom lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatmentis C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and the HAE attackis characterised as “moderate” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as“severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as“severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and whereinthe HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, theHAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI- S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. Dosing Given the serious nature of HAE attacks, and that they can increase in severity such that they can belife-threatening, it is important that any on-demand treatment provides reliably safe and effectivetreatment. The data in Example 4 further confirm that particular dosage regimens of sebetralstat providesuch reliable treatment.The invention therefore also provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). For the avoidance of doubt, any of the embodiments described above in relation to the treatment of severe or worse HAE attacks according to the invention or to the treatment of HAE attacks in patients on prophylactic treatment, or below in relation to the treatment of HAE attacks of the neck and above,specific combination therapies and drug-drug interactions can, where appropriate, be considered incombination with any of the embodiments described herein in relation to dosing. It is intended that any of the embodiments can be combined. Specific embodiments are as follows.Specific dosing regimensIn an embodiment, the first dose is administered on-demand within about 1 hour of recognition of a symptom of an acute HAE attack. In another embodiment, the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised. In an embodiment, the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose. Preferably, the second dose is administered about 3 hours after the first dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose. In an embodiment, a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a third dose to the patient. In an alternative embodiment, the patient is administered a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof).The third dose can be administered between about 2 hours and about 6 hours (more specifically, betweenabout 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the second dose. Preferably, the third dose can be administered about 3 hours after the second dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose. In an embodiment, a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolvedwithout administering a fourth dose to the patient. In an alternative embodiment, the patient isadministered a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose. Preferably, the fourth dose can be administered about 3 hours after the third dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose. In an embodiment, no further dose is administered to the patient, e.g., the attack is resolved without administering any further dose to the patient, in particular, no fifth dose is administered.In any of the above embodiments, each dose is preferably administered as two unit doses. In particular,each unit dose is preferably administered as two tablets (e.g. a film-coated tablet or an orodispersibletablet) each comprising about 300mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof). In any of the embodiments described herein, the patient can also be being treated with a prophylactic treatment of HAE. Specific embodiments wherein the patient is also being treated with a prophylactic treatment of HAE are described above. In any of the above embodiments, the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent. The prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor. The prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist. The prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor. The prophylactic treatment of HAE can be attenuated androgen. In particular, the attenuated androgen can be danazol or oxandrolone. The prophylactic treatment of HAE can be tranexamic acid. Alternatively, the prophylactic treatment of HAE can be non-androgen therapy. The prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In another embodiment, the prophylactic treatment of HAE is C1 inhibitor. In particular, the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®. The prophylactic treatment can be lanadelumab or berotralstat.The prophylactic treatment can be lanadelumab.The prophylactic treatment can be berotralstat.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with aprophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg ofsebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose. In any of the above embodiments, the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals. In an embodiment, the HAE attack is a laryngeal attack. In an embodiment, the HAE attack is an attack of the neck and above. In an embodiment, the HAE attack is an attack of the neck and above but is not a laryngeal attack. In an embodiment, the HAE attackis an abdominal attack. In an embodiment, the HAE attack is a subcutaneous attack. In an embodiment,the HAE attack is an attack of the arms. In an embodiment, the HAE attack is an attack of the hands. In anembodiment, the HAE attack is an attack of the legs. In an embodiment, the HAE attack is an attack of thefeet. In an embodiment, the HAE attack is an attack of the head. In an embodiment, the HAE attack is anattack of the face. In an embodiment, the HAE attack is an attack of the neck. In an embodiment, the HAEattack is an attack of the torso. In an embodiment, the HAE attack is an attack of the genitals.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is a laryngeal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is an abdominal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is a subcutaneous attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is a laryngeal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is an abdominal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is a subcutaneous attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof), and wherein the HAE attack is a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof), and wherein the HAE attack is an abdominal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof), and wherein the HAE attack is a subcutaneous attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administeredbetween about 2 hours and about 6 hours after the second dose, preferably about 3 hours after thesecond dose, and wherein the HAE attack is a laryngeal attack. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after thesecond dose, and wherein the HAE attack is an abdominal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after thesecond dose, and wherein the HAE attack is a subcutaneous attack.In any of the above embodiments, the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “mild” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “moderate” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. Treatment of HAE attacks of the neck and above As noted above, patients with HAE experience unpredictable and often debilitating attacks of tissue swelling that can affect any part of the body and be critical if the upper airways are affected. HAE attacks that begin at the neck and above can lead to laryngeal attacks which can be life-threatening if not treated early. Therefore, it is of paramount importance that on-demand treatments of attacks of the neck and above are effective. In particular, treatment must be fast-acting and provide early intervention to shorten the duration and severity of the attack and lead to faster attack resolution. The barriers associated with current on-demand parenteral therapies means that patients often delay treatment and therefore there is a continued need to provide patients with the confidence that alternative (i.e., non-injectable) therapies will provide effective treatment of attacks of the neck and above. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above. For the avoidance of doubt, any of the embodiments described above in relation to the treatment ofsevere or worse HAE attacks, treatment of HAE attacks in patients on prophylactic treatment, or dosing,or below in relation to specific combination therapies and drug-drug interactions can, where appropriate,be considered in combination with any of the embodiments described herein relation to treatment of HAEattacks of the neck and above. It is intended that any of the embodiments can be combined.Therefore, where appropriate, any of the treatments described herein can be for treating an HAE attack of the neck and above. Specific embodiments are as follows.Specific treatments of HAE attacks of the neck and aboveThe attack of the neck and above can be a facial attack (i.e., an attack of the face) and / or an attack of thetongue and / or an attack of the throat. The attack of the neck and above can be a facial attack. The attackof the neck and above can be an attack of the tongue. The attack of the neck and above can be an attackof the throat. The attack of the neck and above can be a laryngeal attack. The attack of the neck and abovecan be an attack of the throat, and / or the tongue, and / or face. The attack of the neck and above can bean attack of the tongue, and / or the throat, and / or face. The attack of the neck and above can be an attackof the face, and / or the throat, and / or the throat. The attack of the neck and above is an attack of thethroat but is not a laryngeal attack. In any of the above embodiments, the first dose can be administered on-demand within 1 hour of recognition of a symptom of an acute HAE attack. In another embodiment, the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom ofan acute HAE attack being recognised. In an embodiment, a second dose is not administered to the patient, e.g., where the first dose provides sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a second dose to the patient. In an embodiment, the attack of the neck and above is a laryngeal attack and the attack is resolved without administering a second dose to the patient. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or apharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, wherein the attack of the neck and above is a laryngeal attack and the attack is resolved without administering a second dose to the patient. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In an embodiment, the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose. Preferably, the second dose is administered about 3 hours after the first dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose. In an embodiment, a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a third dose to the patient. In an alternative embodiment, the patient is administered a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The third dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the second dose. Preferably, the third dose can be administered about 3 hours after the second dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose. In an embodiment, a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolvedwithout administering a fourth dose to the patient. In an alternative embodiment, the patient isadministered a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose. Preferably, the fourth dose can be administered about 3 hours after the third dose. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose, preferably about 3 hours after the third dose. In an embodiment, no further dose is administered to the patient, e.g., the attack is resolved without administering any further dose to the patient.In any of the above embodiments, each dose is preferably administered as two unit doses. In particular,each unit dose is preferably administered as two tablets (e.g. a film-coated tablet or an orodispersibletablet) each comprising about 300mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE. In any of the above embodiments, the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent. The prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor. The prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist. The prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor. The prophylactic treatment of HAE can be attenuated androgen. In particular, the attenuated androgen can be danazol or oxandrolone. The prophylactic treatment of HAE can be tranexamic acid. Alternatively, the prophylactic treatment of HAE can be non-androgen therapy. The prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In another embodiment, the prophylactic treatment of HAE is C1 inhibitor. In particular, the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®. The prophylactic treatment can be lanadelumab or berotralstat. The prophylactic treatment can be lanadelumab. The prophylactic treatment can be berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg ofsebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose isadministered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is not also being treated with a prophylactic treatment of HAE. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is not also being treated with a prophylactic treatment of HAE. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is not also being treated with a prophylactic treatment of HAE. In any of the above embodiments, the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg ofsebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose isadministered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “mild” or above according to the PGI- S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.Specific treatments of HAE attacks of the neck and above that are not laryngeal attacksAn attack of the neck and above that is not a laryngeal attack can readily progress into a laryngeal attack,which can be life threatening. It is advantageous to treat such attacks to slow the progression into a laryngeal attack. It is advantageous to treat such attacks to reduce the severity of any resulting laryngeal attack. It is advantageous to treat such attacks to prevent the attack from progressing or spreading into a laryngeal attack. Where appropriate, any of the treatments described herein can therefore be for treatingan attack of the neck and above that is not a laryngeal attack. Specific embodiments are as follows. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demandcomprising: orally administering a first dose of about 600mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attackis an attack of the neck and above, and wherein the attack of the neck and above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the attack of theneck and above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hoursafter the first dose, and wherein the attack of the neck and above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the attack ofthe neck and above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the attack of the neckand above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof),and wherein the attack of the neck and above is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a third dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a fourth dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose,preferably about 3 hours after the third dose and wherein the attack of the neck and above is not alaryngeal attack.In any of the above embodiments wherein the attack of the neck and above is not a laryngeal attack,sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) slows the progression of theattack into a laryngeal attack. In another embodiment wherein the attack of the neck and above is not alaryngeal attack, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) reduces the severity of any resulting laryngeal attack. In another embodiment wherein the attack of the neck andabove is not a laryngeal attack, prevents the attack from progressing into a laryngeal attack.Specific combination therapiesAs mentioned above, the data described herein show that sebetralstat (a plasma kallikrein inhibitor) canbe used on-demand to treat HAE attacks in patients who are also being treated with a prophylactic HAEtreatment (even when the prophylactic treatment is also a plasma kallikrein inhibitor), in particular wherethe HAE attack is a severe or very severe attack and / or where the HAE attack is an attack of the neck andabove but is not a laryngeal attack. The attack of the neck and above can be a facial attack (i.e., an attackof the face) and / or an attack of the tongue and / or an attack of the throat. It is important that a broadrange of HAE patients and a wide range of HAE attacks can benefit from on-demand treatment. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack.The attack of the neck and above can be a facial attack and / or an attack of the throat and / or an attack ofthe tongue. Any of the embodiments described above in relation to in relation to the treatment of severe or worse HAE attacks, treatment of HAE attacks in patients on prophylactic treatment, or dosing, or below inrelation to drug-drug interactions can, where appropriate, be considered in combination with any of theembodiments described herein relation to specific combination therapies. It is intended that any of the embodiments can be combined. Specific combination therapies are as follows. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “very severe” according to the PGI-S scale. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the HAE attackis selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, and asubcutaneous attack. The HAE attack can be a laryngeal attack. The HAE attack can be an attack of the neck and above. The HAE attack can be an abdominal attack. The HAE attack can be a subcutaneous attack. The HAE attack can bean attack of the neck and above but is not a laryngeal attack.The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, and wherein the HAE attack is characterised as“mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, and wherein the HAE attack is characterised as“severe” or above according to the PGI-S scale. In any of the above embodiments, the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent. The prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor.The data in Example 4 show that sebetralstat (a plasma kallikrein inhibitor) is safe and effective at treatingHAE attacks even when the patient is already taking a different plasma kallikrein inhibitor as a prophylactictreatment (specifically, lanadelumab or berotralstat). This is advantageous and demonstrates theusefulness and a reliability of sebetralstat (a plasma kallikrein inhibitor) in a wide range of relevant clinicalcircumstances e.g. even when a patient is taking a plasma kallikrein inhibitor prophylactic treatment.The prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist. The prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor. The prophylactic treatment of HAE can be attenuated androgen. In particular, the attenuated androgen can be danazol or oxandrolone. The prophylactic treatment of HAE can be tranexamic acid. Alternatively, the prophylactic treatment of HAE can be non-androgen therapy. The prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. In an embodiment, the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The prophylactic treatment of HAE can be C1 inhibitor. In particular, the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®. The prophylactic treatment can be lanadelumab or berotralstat. The prophylactic treatment can be lanadelumab. The prophylactic treatment can be berotralstat. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is a FactorXIIa (FXIIa) inhibitor. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is a plasma kallikrein inhibitor. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is a plasmakallikrein inhibitor. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selectedfrom lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selectedfrom lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selectedfrom lanadelumab and berotralstat. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is lanadelumab. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment islanadelumab. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on- demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is berotralstat. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment isberotralstat. The invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is anattack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is C1INHreplacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®). Drug-drug interactions The data disclosed herein demonstrate that a drug-drug interaction occurs when sebetralstat (or pharmaceutically acceptable salt and / or solvate thereof) is administered with a strong or moderate CYP3A4 inhibitor or a CYP3A4 inducer. In particular, concomitant administration of a strong or moderateCYP3A4 inhibitor or a strong or moderate CYP3A4 inducer affects the blood levels of sebetralstat (orpharmaceutically acceptable salt and / or solvate thereof). Concomitant administration of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) and a CYP3A4 inhibitor has the potential to increase or prolong the effects of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). Concomitant administration of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) and a CYP3A4 inducer has the potential to decrease or shorten the effects of sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof). It may be desirable to account for these interactions with adequate dose adjustments.The invention therefore provides a method for treating an attack of hereditary angioedema (HAE)on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / orsolvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inhibitor and wherein the method comprises reducing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inducer and wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). For the avoidance of doubt, any of the embodiments described above in relation to the treatment ofsevere or worse HAE attacks, treatment of HAE attacks in patients on prophylactic treatment, dosing, thetreatment of HAE attacks of the neck and above, or specific combination therapies can, whereappropriate, be considered in combination with any of the embodiments described herein relation todrug-drug interactions. It is intended that any of the embodiments can be combined. Concomitant administration can mean that the sebetralstat and the CYP3A4 inhibitor / inducer are administered simultaneously, separately or sequentially. For the avoidance of doubt, sebetralstat and the CYP3A4 inhibitor / inducer are not necessarily given at the same time, i.e., sebetralstat and the CYP3A4inhibitor / inducer can be given at different times of the day.As used in the context of this drug-drug interaction section, a “strong CYP3A4 inhibitor” is a drug that increases the AUC of sensitive index substrates of a given metabolic pathway ≥ 5-fold. As used herein, a “moderate CYP3A4 inhibitor” is a drug that increases the AUC of sensitive index substrates of a givenmetabolic pathway by ≥ 2- to < 5-fold. As used herein, a “strong CYP3A4 inducer” is a drug that decreasesthe AUC of sensitive index substrates of a given metabolic pathway by ≥ 80 percent. As used herein, a“moderate CYP3A4 inducer” is a drug that decreases the AUC of sensitive index substrates of a givenmetabolic pathway by ≥ 50 percent to < 80 percent. These definitions are in accordance with the FDAdefinition (https: / / www.fda.gov / media / 134581 / download - see pages 23-24) and the EMA definition(https: / / www.ema.europa.eu / en / documents / scientific-guideline / guideline-investigation-drug-interactions-revision-1_en.pdf - see Appendix VIII).Specific treatments to account for potential drug-drug interactions The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inhibitor and wherein the method comprises reducing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) so as to diminish the additive effect experienced when co-administered with the strong or moderate CYP3A4 inhibitor. In an embodiment, the additive effect is an increased therapeutic effect of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In any of the above embodiments, the dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is reduced by about 10% to about 60% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is reduced by about 20% to about 50% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is reduced by about 30% to about 50% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is reduced by about 40% to about 50% of the normal dose for the patient. In particular, the dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is reduced by about 50% of the normal dose for the patient.In any of the above embodiments, the “normal dose” for the patient is preferably 600mg.In some embodiments, the CYP3A4 inhibitor is a strong CYP3A4 inhibitor. The strong CYP3A4 inhibitor can be selected from itraconazole, ketoconazole, ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, lopinavir and ritonavir, clarithromycin, ceritinib, cobicistat, idelalisib, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and / or dasabuvir), posaconazole, saquinavir and ritonavir, telithromycin, tipranavir and ritonavir, voriconazole, darunavir , telaprevir, stiripentol, curcumin, troleandomycin, atazanavir, naloxone, nilotinib, delavirdine, loperamide, ribociclib, danoprevir, midostaurin, terfenadine, ergotamine, econazole, ditiocarb, methimazole, boceprevir, lonafarnib, amprenavir, amiodarone, and levoketoconazole. In other embodiments, the CYP3A4 inhibitor is a moderate CYP3A4 inhibitor. The moderate CYP3A4 inhibitor can be selected from verapamil, aprepitant, ciprofloxacin, conivaptan, crizotinib, diltiazem, dronedarone, erythromycin, fluconazole, grapefruit juice, imatinib, isavuconazole, isavuconazonium, luliconazole, netupitant, miconazole, nicardipine, isoniazid, danazol, lovastatin, ziprasidone, desvenlafaxine, indalpine, zimelidine, milnacipran, fusidic acid, barnidipine, benidipine, isradipine, haloperidol, linagliptin, fosnetupitant, simeprevir, nilvadipine, primaquine, clozapine, tioconazole, venetoclax, seproxetine, fluvoxamine, fosamprenavir, cyclosporine, abiraterone, clindamycin, berotralstat, tepotinib, and lenacapavir. The invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inducer and wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) so as to compensate for the effect experienced during co-administration. In an embodiment, the effect experienced during co-administration is a decreased therapeutic effect of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). In any of the above embodiments, the dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is increased by about 10% to about 60% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is increased by about 20% to about 50% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is increased by about 30% to about 50% of the normal dose for the patient. The dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is increased by about 40% to about 50% of the normal dose for the patient. In particular, the dose of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is increased by about 50% of the normal dose for the patient. In any of the above embodiments, the “normal dose” for the patient is preferably 600mg. In some embodiments, the CYP3A4 inducer is a strong CYP3A4 inducer. The strong CYP3A4 inducer can be selected from 3-phenytoin, fosphenytoin, apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor and ivacaftor, mitotane, rifampin, St. John’s wort, pentobarbital, phenobarbital, enzalutamide, rimexolone, rifaximin, rifamycin, midostaurin, dexamethasone, and rifapentine. In other embodiments, the CYP3A4 inducer is a moderate CYP3A4 inducer. The moderate CYP3A4 inducer can be selected from efavirenz, bosentan, cenobamate, dabrafenib, etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib, modafinil, nafcillin, bexarotene, avasimibe, echinacea, dexamethasone, and dexamethasone acetate. Further embodiments that apply to any of the treatments described herein In any of the treatments of the invention described herein, sebetralstat is orally administered in a therapeutically effective amount. Unless stated otherwise, the therapeutically effective amount can bebetween about 100 mg and about 1500 mg, about 300 mg and about 1800 mg, about 100 mg and about1400 mg, about 200 mg and about 1200 mg, about 300 mg and about 1200 mg, about 600 mg and about 1200 mg, about 450 mg and about 900 mg, about 500 mg and about 1000 mg, about 450 mg and about 600 mg, about 500 mg and about 700 mg (more specifically, 600 mg), about 800 mg and about 1000 mg per day, about 900 mg and about 1400 mg (more specifically 1200 mg), or about 900 mg and about 1200mg. The therapeutically effective amount can be between about 540 mg and about 660 mg, betweenabout 550 mg and about 650 mg, between about 575 mg and about 625 mg, between about 585 mg and about 615 mg, between about 590 mg and about 610 mg, or between about 595 mg and about 605 mg.Preferably the therapeutically effective amount is about 600 mg. As used herein, “about” means ± 10%.In any of the embodiments described herein, the sebetralstat is preferably in the free base form.In any of the embodiments described herein, the patient can be aged 12 years and above. In particular, the patient can be aged between 12 and less than 18. Alternatively, the patient can be aged 18 years and above. In any of the embodiments described herein, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is administered to reduce the time to beginning of symptom relief. The term “symptom relief” in this context can mean that the attack is rated as “a little better” or higher for two consecutive time points when assessed according to the PGI-C scale. PGI-C is a known index in the art that can be used to score the progression of an HAE attack and to report attacks as “much better”, “better”, “a little better”, “no change”, “a little worse”, “worse”, or “much worse”. When assessed using the PGI-C scale, in any of the treatments of the invention, sebetralstat isadministered to reduce the time to beginning of symptom relief to between about 1 and about 8 hoursafter the first dose of sebetralstat. Symptom relief can start between about 1 and about 5 hours after thefirst dose. Symptom relief can start between about 1 and about 6 hours after the first dose of sebetralstat.Symptom relief can start between about 1 and about 4 hours after the first dose of sebetralstat. Symptomrelief can start between about 1 and about 2 hours after the first dose. Symptom relief can start betweenabout 1.5 and about 1.8 hours after the first dose. Symptom relief can start at about 1.79 hours after thefirst dose of sebetralstat. In any of the embodiments described herein, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is administered to reduce the time to a reduction in attack severity. The term “reduction in attack severity” in this context can mean that the attack severity decreases from baseline by one or more levels on the PGI-S scale for two consecutive time points. When assessed using the PGI-S scale, in any of the treatments of the invention, sebetralstat isadministered to reduce the time to a reduction in attack severity to between about 1 and about 12 hours.Reduction in attack severity can start between about 2 and about 11 hours. Reduction in attack severitycan start between about 3 and about 10 hours. Reduction in attack severity can start between about 5and about 10 hours. Reduction in attack severity can start between about 5 and about 8 hours. Reductionin attack severity can start between about 7 and about 8 hours. Reduction in attack severity can start atabout 7.75 hours.In any of the embodiments described herein, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) is administered to achieve complete attack resolution. The term “complete attack resolution” in this context can mean that the treatment improves the severity of the attack to “none” when assessed using the PGI-S scale. When assessed using the PGI-S scale, in any of the treatments of the invention, sebetralstat isadministered to achieve complete attack resolution within about 7 and about 24 hours. Complete attackresolution can be achieved within 24 hours. Complete attack resolution can be achieved within about 7and about 20 hours. Complete attack resolution can be achieved within about 7 and about 17 hours.Complete attack resolution can be achieved within about 7 and about 12 hours. Complete attackresolution can be achieved within about 7 and about 10 hours.Dosage forms that can be used in the treatments described hereinIn any of the embodiments described herein, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) can preferably be administered as part of a pharmaceutical composition. Sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) can administered as an oral dosage formcomprising: (i) sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and (ii) at leastone pharmaceutically acceptable excipient. The oral dosage form can be a capsule. The oral dosage formcan be a tablet. In particular, the tablet can be a film-coated tablet or an orodispersible tablet. The oral dosage form can be a film-coated tablet comprising microcrystalline cellulose as a diluent, croscarmellose sodium as a disintegrant, polyvinyl pyrrolidone as a binder, and optionally magnesiumstearate as a lubricant. In a preferred tablet, sebetralstat comprises: (i) at least about 40 wt% of the tablet(more specifically about 40 wt% to about 60 wt%), compared to the total mass of the tablet; (ii) about 25wt% to about 60 wt% of the diluent (more specifically about 25 wt% to about 40 wt%, compared to thetotal mass of the tablet; (iii) about 1 wt% to about 15 wt% of the disintegrant (more specifically about 2wt% to about 6 wt%), compared to the total mass of the tablet; (iv) about 1 wt% to about 20 wt% of the binder (more specifically about 2 wt% to about 5 wt%), compared to the total mass of the tablet; andwhen present, (v) about 0.1 to about 5 wt% lubricant (more specifically about 0.1 wt% to about 1.5 wt%),compared to the total mass of the tablet. The dosage form can be a tablet containing about 250mg toabout 350mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The dosageform can be a tablet containing about 270mg to about 330mg of sebetralstat (or a pharmaceuticallyacceptable salt and / or solvate thereof). The dosage form can be a tablet containing about 275mg to about325mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The dosage formcan be a tablet containing about 285mg to about 315mg of sebetralstat (or a pharmaceutically acceptablesalt and / or solvate thereof). The dosage form can be a tablet containing about 290mg to about 310mg ofsebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The dosage form can be atablet containing about 295mg to about 305mg of sebetralstat (or a pharmaceutically acceptable saltand / or solvate thereof). Preferably, the dosage form can be a tablet containing about 300mg ofsebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof). The tablet can further comprise extragranular excipients comprising: microcrystalline cellulose as an extragranular diluent, croscarmellose sodium as an extragranular disintegrant, polyvinyl pyrrolidone as an extragranular binder, and / or magnesium stearate as an extragranular lubricant. The dosage forms described herein (e.g. the tablets) can be film coated, wherein the film coating can comprise one or more of hypromellose, lactose monohydrate, titanium dioxide and triacetin.In any of the embodiments described herein, sebetralstat is administered as an orodispersible tablet. Theorodispersible tablet can comprise one or more of mannitol (e.g. granulated mannitol and / or spray-dried mannitol (e.g. Mannogem EZ®)) as a filler, microcrystalline cellulose (e.g. silicified microcrystalline cellulose) as a binder and polyvinylpyrrolidone (crospovidone) as a disintegrant. In particular, the orodispersible tablet can comprise between about 25 and about 50 wt% of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), one or more fillers (e.g. granulated mannitol and / or spray-dried mannitol) present at between about 30 and 80 wt% of the orodispersible tablet, one or more binders (e.g. silicified microcrystalline cellulose) present at between about 5 and about 30 wt% of the orodispersible tablet and one or more disintegrants (e.g. polyvinylpyrrolidone (crospovidone)) present at between 1 and about 10 wt% of the orodispersible tablet. Symptoms In the treatments of the invention, sebetralstat (or a pharmaceutically acceptable salt and / or solvatethereof) can be orally administered on-demand upon recognition of a symptom of an HAE attack. In thetreatments of the invention, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof)can be orally administered on-demand at the earliest recognition of an HAE attack. In the treatments ofthe invention, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) can be orallyadministered on-demand for the treatment of patient-recognized attacks of HAE.Although each HAE attack can be different in severity and in terms of the area affected, patients who suffer from HAE, medical professionals with knowledge of HAE, and carers of HAE patients are (and indeed the skilled person would be) astute in identifying symptoms of an HAE attack. These symptoms include, but are not limited to: swelling of tissues such as in the hands, feet, limbs, face, intestinal tract, and / or airway; fatigue; headache; muscle aches; skin tingling; abdominal pain; nausea; vomiting; diarrhoea; difficulty swallowing; hoarseness; shortness of breath; and / or mood changes. Thus, in some embodiments, administration of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) can occur upon recognition of at least one of the above symptoms. The skilled person would also understand that “administered upon recognition of a symptom of a HAE attack” means that administration occurs as quickly as feasibly possible after the symptom of an HAE attack is recognised. For example, patients are expected to have sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) easily and readily available at all times (most likely in the form of a pharmaceutically acceptable composition) to ensure that treatment can occur upon recognition of a symptom of a HAE attack. In other words, the treatment occurs on-demand. For example, sebetralstat can be administered within 1 hour of the symptom of an HAE attack being recognised, preferably within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised. If the symptom of an HAE attack is recognised in the prodromal phase, sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) can be administered in the prodromal phase of an HAE attack. In these circumstances, the symptom recognised can be a slight swelling, in particular, a slight swelling affecting the face and neck. In addition, or in the alternative, the symptom can be abdominal pain, in particular, abdominal pain is considered to be characteristic of a HAE attack. In addition, or in the alternative, the symptom can be a reddening of the skin such as erythema marginatum. In any of the above treatments, the symptom can be recognised by the patient. In any of the above treatments, the symptom can be recognised by a medical professional such as a medical professional with knowledge of HAE. In any of the above treatments, the symptom can be recognised by a carer of the patient. Figures In the Figures, the term “Compound” means sebetralstat.Figure 1: X-ray powder diffraction pattern of the sebetralstat as generated in Example 1.Figure 2: Chart showing the distribution of attack severity (PGI-S) at baseline in patients using on-demandtreatment ± LTP.Figure 3: Chart showing the distribution of attack severity (PGI-S) at baseline in patients using sebetralstat600mg or placebo.Figure 4: Graph showing the time from onset of attack to the first IMP administration.Graph showing the cumulative % of patients with symptom relief (PGI-C) within 12 hours of IMPFigure 6: Graph showing the cumulative % of patients with a reduction in attack severity (PGI-S) within12 IMP administration.7: showing the cumulative % of patients with complete attack resolution (PGI-S) within24 IMP administration.showing the cumulative % of patients with a 50% reduction in composite VAS score within24 hours of IMP administration.Figure 9: Graph showing the plasma concentration of sebetralstat when administered alone and with thestrong CYP3A4 inhibitor itraconazole.Figure 10: Graph showing the plasma concentration of sebetralstat when administered alone and withthe strong CYP3A4 inhibitor itraconazole.Figure 11: Graph showing the plasma concentration of sebetralstat when administered alone and withthe strong CYP3A4 inducer phenytoin. Graph showing the plasma concentration of sebetralstat when administered alone and withthe strong CYP3A4 inducer phenytoin.Figure 13: Graph showing the plasma concentration of sebetralstat when administered alone and withthe moderate CYP3A4 inhibitor verapamil. Graph showing the plasma concentration of sebetralstat when administered alone and withthe moderate CYP3A4 inhibitor verapamil.Figure 15: Graph showing the plasma concentration of sebetralstat when administered alone and withthe moderate CYP3A4 inducer efavirenz.Figure 16: Graph showing the plasma concentration of sebetralstat when administered alone and withthe moderate CYP3A4 inducer efavirenz. Figure 17: Graph showing proportion of attacks reaching primary or key secondary endpoints with 1 or 2 administrations of sebetralstat. Figure 18: Graph showing hazard ratios of sebetralstat 600 mg compared with 300 mg for primary or keysecondary endpoints by baseline attack severity.Figure 19: Graph showing hazard ratios of sebetralstat 600 mg compared with 300 mg for primary or keysecondary endpoints by treatment paradigm.Figure 20: Graph showing number of sebetralstat-treated attacks in the open-label extension Phase 3study of sebetralstat (Example 5).Figure 21: Graph showing time from attack recognition to sebetralstat administration in the open-labelextension Phase 3 study of sebetralstat (Example 5). Figure 22: Graph showing time from onset of attack to treatment administration (Example 4).Figure 23: Graph showing the probability for faster complete attack resolution (Example 4).Figure 24: Graph showing time to complete attack resolution within 24 hours versus time to treatment for “mild”, or “moderate” or greater, attacks treated “earlier” and “later” (Example 4).Figure 25: LOESS regression curve fitting time to complete attack resolution within 24 hours versus timeto treatment (Example 4). Figure 26: Graph showing baseline attack severity in attacks involving the larynx (Examples 4 and 5). Figure 27: Graph showing time to treatment administration in all attacks treated in Example 4, all attacks treated in Example 5 and attacks involving the larynx treated in Examples 4 and 5. Figure 28: Graph showing the proportion of attacks involving the larynx that reached primary and key secondary endpoints without an additional dose (Examples 4 and 5).Figure 29: Graph showing sebetralstat effectiveness among participants receiving LTP in the open-labelextension Phase 3 study of sebetralstat (Example 5).Figure 30: Graph showing sebetralstat effectiveness among participants receiving berotralstat in theopen-label extension Phase 3 study of sebetralstat (Example 5). Figure 31: Graph showing effectiveness endpoints in attacks involving the larynx treated with sebetralstat in the open-label extension Phase 3 study of sebetralstat (Example 5). Embodiments provided herein may be more fully understood by reference to the following examples.These examples are meant to be illustrative of treatments provided herein but are not in any way limiting.Indeed, the scope of the invention is defined by the claims. While examples of certain particular embodiments are provided herein, it will be apparent to those skilled in the art that various changes and modifications may be made. Such modifications are also intended to fall within the scope of the appended claims. General Experimental Details In the following examples, the following abbreviations and definitions are used: Aq Aqueous solutionDCM DichloromethaneDDI Drug-drug interactionDMF N,N-DimethylformamideEtOAc Ethyl AcetateFXII Factor XIIFXIIa Factor XIIaHAE Hereditary angioedemaHK High molecular weight kininogenHrs HoursHOBt HydroxybenzotriazoleIMP Investigational Medicinal ProductIPA 2-Propanol / Propan-2-ol / Iso-propanolLCMS Liquid chromatography mass spectrometryLTP Long-term prophylaxisMe MethylMeCN AcetonitrileMeOH MethanolMin MinutesMS Mass spectrum Nuclear magnetic resonance spectrum – NMR spectra were recorded at aNMR frequency of 400MHz unless otherwise indicated ODT Orodispersible tabletPh PhenylPKa Plasma kallikreinPPK Plasma prekallikreinN-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2- Sebetralstat oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide Rt room temperatureTHF TetrahydrofuranXRPD X-ray powder diffractionAll reactions were carried out under an atmosphere of nitrogen unless specified otherwise.1H NMR spectra were recorded on a Bruker (400MHz) or on a JEOL (400MHz) spectrometer with referenceto deuterium solvent and at rt. Molecular ions were obtained using LCMS which was carried out using a Chromolith Speedrod RP-18e column, 50 x 4.6 mm, with a linear gradient 10% to 90% 0.1% HCO2H / MeCN into 0.1% HCO2H / H2O over 13 min, flow rate 1.5 mL / min, or using Agilent, X-Select, acidic, 5-95% MeCN / water over 4 min. Data was collected using a Thermofinnigan Surveyor MSQ mass spectrometer with electospray ionisation in conjunction with a Thermofinnigan Surveyor LC system. Alternatively, molecular ions were obtained using LCMS which was carried out using an Agilent Poroshell 120 EC-C18 (2.7μm, 3.0 x 50mm) column with 0.1% v / v Formic acid in water [eluent A]; MeCN [eluent B]; Flow rate 0.8mL / min and 1.5 minutes equilibration time between samples, gradient shown below. Mass detection was afforded with API 2000 mass spectrometer (electrospray). Gradient: Time (min) Eluent A (%) Eluent B (%)0.00 95 50.20 95 52.00 5 953.00 5 953.25 95 53.50 95 5Where products were purified by flash chromatography, ‘silica’ refers to silica gel for chromatography, 0.035 to 0.070 mm (220 to 440 mesh) (e.g. Merck silica gel 60), and an applied pressure of nitrogen up to 10 p.s.i accelerated column elution. Reverse phase preparative HPLC purifications were carried out using a Waters 2525 binary gradient pumping system at flow rates of typically 20 mL / min using a Waters 2996 photodiode array detector. All solvents and commercial reagents were used as received. Chemical names were generated using automated software such as the Autonom software provided as part of the ISIS Draw package from MDL Information Systems or the Chemaxon software provided as a component of MarvinSketch or as a component of the IDBS E-WorkBook. X-Ray Powder Diffraction patterns were collected on a Philips X-Pert MPD diffractometer and analysed using the following experimental conditions (Method A), unless otherwise specified: Tube anode: Cu Generator tension: 40 kV Tube current: 40 mA Wavelength alpha1: 1.5406 Å Wavelength alpha2: 1.5444 Å Start angle [2θ]: 4 End angle [2θ]: 40 Continuous scan Approximately 2 mg of sample under analysis was gently compressed on the XRPD zero back ground single obliquely cut silica sample holder. The sample was then loaded into the diffractometer for analysis.Example 1 – Preparation of sebetralstatA.1-(4-Hydroxymethyl-benzyl)-1H-pyridin-2-one4-(Chloromethyl)benzylalcohol (5.0 g, 31.93 mmol) was dissolved in acetone (150 mL).2-hydroxypyridine(3.64 g, 38.3 mmol) and potassium carbonate (13.24 g, 95.78 mmol) were added and the reaction mixturewas stirred at 50 °C for 3 hrs after which time the solvent was removed in vacuo and the residue taken upin chloroform (100 mL). This solution was washed with water (30 mL), brine (30 mL), dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica), eluent 3% MeOH / 97% CHCl3, to give a white solid identified as 1-(4-hydroxymethyl-benzyl)-1H-pyridin-2-one (5.30g, 24.62mmol, 77% yield). [M+Na]+= 238 B.1-(4-Chloromethyl-benzyl)-1H-pyridin-2-one 1-(4-Hydroxymethyl-benzyl)-1H-pyridin-2-one (8.45 g, 39.3 mmol), dry DCM (80 mL) and triethylamine (7.66 ml, 55.0 mmol) were cooled in an ice bath. Methanesulfonyl chloride (3.95 ml, 51.0 mmol) was added and stirred in ice bath for 15 min. The ice bath was removed and stirring continued at rt temperature overnight. The reaction mixture was partitioned between DCM (100 mL) and saturated aqueous NH4Cl solution (100 mL). The aqueous layer was extracted with further DCM (2 x 50 mL) and the combined organics washed with brine (50 mL), dried over Na2SO4, filtered and concentrated to give 1-(4- chloromethyl-benzyl)-1H-pyridin-2-one (8.65 g, 36.6 mmol, 93 % yield) as a pale yellow solid. [MH]+= 234.1 C. Methyl 3-(methoxymethyl)-1-(4-((2-oxopyridin-1(2H)-yl)methyl)benzyl)-1H-pyrazole-4-carboxylate Potassium carbonate (519 mg, 3.76 mmol) was added to a solution of methyl 3-(methoxymethyl)-1H- pyrazole-4-carboxylate (320 mg, 1.88 mmol; CAS no.318496-66-1 (synthesised according to the method described in WO 2012 / 009009)) and 1-(4-(chloromethyl)benzyl)pyridin-2(1H)-one (527 mg, 2.26 mmol) in DMF (5 mL) and heated at 60 °C overnight. The reaction mixture was diluted with EtOAc (50 mL) and washed with brine (2 x 100 mL), dried over magnesium sulfate, filtered and reduced in vacuo. The crude product was purified by flash chromatography (40 g column, 0-100% EtOAc in isohexanes) to afford two regioisomers. The second isomer off the column was collected to afford methyl 3-(methoxymethyl)-1-(4- ((2-oxopyridin-1(2H)-yl)methyl)benzyl)-1H-pyrazole-4-carboxylate (378 mg, 1.01 mmol, 53.7 % yield) as a colourless gum. [MH]+= 368.2 D.3-(Methoxymethyl)-1-(4-((2-oxopyridin-1(2H)-yl)methyl)benzyl)-1H-pyrazole-4-carboxylic acid To methyl 3-(methoxymethyl)-1-(4-((2-oxopyridin-1(2H)-yl)methyl)benzyl)-1H-pyrazole-4-carboxylate (3.77 g, 10.26 mmol) in THF (5 mL) and MeOH (5 mL) was added 2M NaOH solution (15.39 ml, 30.8 mmol) and stirred at rt overnight.1M HCl (50 mL) was added and extracted with EtOAc (50 mL). The organic layerwas washed with brine (50 mL), dried over magnesium sulfate, filtered and reduced in vacuo to give 3-(methoxymethyl)-1-(4-((2-oxopyridin-1(2H)-yl)methyl)benzyl)-1H-pyrazole-4-carboxylic acid (1.22 g, 3.45 mmol, 33.6 % yield) as a white powder. [MH]+= 354.2 E.3-Fluoro-4-methoxy-pyridine-2-carbonitrile To a large microwave vial, copper (I) cyanide (1.304 g, 14.56 mmol) was added to a solution of 2-bromo- 3-fluoro-4-methoxypyridine (1 g, 4.85 mmol) in DMF (5 mL). The reaction vial was sealed and heated to 100 °C for 16 hrs. The reaction mixture was diluted with water (20 mL) and EtOAc (20 mL). The thicksuspension was sonicated and required additional water (40 mL) and EtOAc (2 x 50 mL) with sonication tobreak-up the solid precipitated. The combined layers were filtered through a plug of celite and the organic layer isolated, washed with brine (50 mL), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure to give a pale green solid identified as the desired compound 3-fluoro-4-methoxy-pyridine-2-carbonitrile (100 mg, 0.578 mmol, 12 % yield)F. (3-Fluoro-4-methoxy-pyridin-2-ylmethyl)-carbamic acid tert-butyl ester3-Fluoro-4-methoxy-pyridine-2-carbonitrile (100 mg, 0.578 mmol) was dissolved in anhydrous methanol(10 mL, 247 mmol) and nickel chloride hexahydrate (14 mg, 0.058 mmol) was added followed by di-tert- butyl dicarbonate (255 mg, 1.157 mmol). The resulting pale green solution was cooled in an ice-salt bath to -5 °C and then sodium borohydride (153 mg, 4.05 mmol) was added portion wise maintaining the reaction temperature ~0 °C. The deep brown solution was left to stir at 0 °C and slowly allowed to warm to rt and then left to stir at rt for 3 hrs. The reaction mixture was evaporated to dryness at 40 °C to afford a black residue which was diluted with DCM (10 mL) and washed with sodium hydrogen carbonate (10mL). An emulsion formed so the organics were separated via a phase separating cartridge andcon...

Claims

CLAIMS 1. A method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orallyadministering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.

2. The method according to claim 1, wherein the patient is administered a first dose of about600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof).

3. The method according to claim 2, wherein the patient is administered a second dose of about600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof).

4. The method according to claim 3, wherein the second dose is administered between about 2hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.

5. The method according to any of claims 1 to 4, wherein the patient is also being treated with aprophylactic treatment of HAE.

6. A method for treating an attack of hereditary angioedema (HAE) on demand comprising: orallyadministering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE.

7. The method according to claim 6, wherein the prophylactic treatment is selected from a PKabinding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent.

8. The method according to claim 6, wherein the prophylactic treatment is a Factor XIIa (FXIIa)inhibitor.

9. The method according to claim 6, wherein the prophylactic treatment is a plasma kallikreininhibitor.

10. The method according to claim 6, wherein the prophylactic treatment is selected fromlanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.

11. The method according to any of claims 6 to 10, wherein the second dose is administeredbetween about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.

12. A method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orallyadministering sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof) followed by a second dose of about 600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof), wherein the second dose is administered about 3 hours after the first dose.

13. The method according to claim 12, wherein the patient is administered a third dose of about600mg of sebetralstat (or a pharmaceutically acceptable salt and / or solvate thereof).

14. The method according to claim 13, wherein the third dose is administered between about 2hours and about 6 hours after the second dose, preferably about 3 hours after the second dose.

15. The method according to any of claims 6 to 14, wherein the HAE attack is characterised as“mild” or above according to the PGI-S scale.

16. The method according to any of claims to 6 to 14, wherein the HAE attack is characterised as“moderate” or above according to the PGI-S scale.

17. The method according to claims to 6 to 14, wherein the HAE attack is characterised as “severe”or above according to the PGI-S scale.

18. The method according to any of claims 6 to 17, wherein the first dose is administeredon-demand upon recognition of a symptom of an HAE attack.

19. The method according to any of claims 6 to 18, wherein the first dose is administeredon-demand within about 1 hour of recognition of a symptom of an acute HAE attack.

20. The method according to claim 19, wherein the first dose is administered on-demand withinabout 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised.

21. The method according to any of claims 1 to 20, wherein sebetralstat is in free base form.

22. The method according to any of claims 1 to 21, wherein the HAE attack is selected from alaryngeal attack, an attack of the neck and above, an attack of the neck and above that is not a laryngeal attack, an abdominal attack, and a subcutaneous attack.

23. The method according to claim 22, wherein the HAE attack is an attack of the neck and abovethat is not a laryngeal attack.

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