METHOD OF TREATING HIDRADENTITIS SUPPURATIVA WITH IL-17 ANTAGONISTS
The present disclosure relates to methods for treating Hidradenitis Suppurativa (HS) using IL-17 antagonists, e. g., secukinumab. Also disclosed herein are IL-17 antagonists, e.g., IL-17 antibodies, such as secukinumab, for treating HS patients, as well as medicaments, dosing regimens, pharmaceutical formulations, dosage forms, and kits for use in the disclosed uses and methods.
1 - 46 . (canceled)
47 . A method of treating hidradenitis suppurativa (HS), comprising subcutaneously (SC) administering to a patient in need thereof a dose of about 300 mg of an IL-17 antibody, or an antigen-binding fragment thereof, weekly during weeks 0, 1, 2, and 3, and thereafter SC at a dose of about 300 mg every other week (every 2 weeks), beginning during week 4;
wherein the IL-17 antibody or antigen-binding fragment thereof comprises:
i) an immunoglobulin V H domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin V L domain comprising the amino acid sequence set forth as SEQ ID NO:10;
ii) an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or
iii) an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;
and wherein the IL-17 antibody or antigen-binding fragment thereof binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Va1124, Thr125, Pro126, Ile127, Va1128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL-17 antibody has a K D of about 100-200 pM as measured by a biosensor system, and wherein the IL-17 antibody has an in vivo half-life of about 23 to about 30 days.
48 . The method according to claim 47 , wherein said patient achieves a sustained response after one year of treatment, as measured by inflammatory lesion count, Hidradenitis Suppurativa Clinical Response (HiSCR), Numerical Rating Scale (NRS), modified Sartorius HS score, Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA), or Dermatology Life Quality Index (DLQI).
49 . The method according to claim 47 , wherein said patient achieves a sustained response after one year of treatment, as measured by the simplified HiSCR (sHiSCR).
50 . The method according to claim 47 , wherein, prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient has been previously treated with a systemic agent for HS.
51 . The method according to claim 50 , wherein the systemic agent is selected from the group consisting of a topical treatment, an antibiotic, an immune system suppressant, a TNF-alpha inhibitor, an IL-1 antagonist, and combinations thereof.
52 . The method according to claim 47 , wherein the IL-17 antibody or antigen-binding fragment is administered in combination with at least one of a TNF-alpha inhibitor, an antibiotic, an IL-1 inhibitor, or an immunosuppressant.
53 . The method according to claim 47 , wherein the patient has moderate to severe HS.
54 . The method according to claim 47 , wherein, prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient has an HS-PGA score of ≥3.
55 . The method according to claim 47 , wherein, prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient is classified under Hurley stage II or III.
56 . The method according to claim 47 , wherein said patient achieves a simplified HiSCR by week 16 of treatment.
57 . The method according to claim 47 , wherein, by week 16 of treatment, said patient achieves an NRS30 and/or a reduction of <6 as measured by the DLQI.
58 . The method according to claim 47 , wherein, prior to treatment with the IL-17 antibody or antigen-binding fragment thereof, the patient does not have extensive scarring (<20 fistulas) as a result of HS.
59 . The method according to claim 47 , wherein the patient is additionally treated with at least one topical medication and at least one antiseptic in combination with the IL-17 antibody or antigen-binding fragment thereof.
60 . The method according to claim 47 , wherein, as early as one week after the first dose of the IL-17 antibody or antigen-binding fragment thereof, the patient has a rapid reduction in:
a) pain, as measured by VAS or NRS, and/or
b) CRP, as measured using a standard CRP assay.
61 . The method according to claim 47 , wherein the patient has a reduction in modified Sartorius score and/or an improvement in DLQI by 16 weeks of treatment.
62 . The method according to claim 47 , wherein the IL-17 antibody or antigen-binding fragment is secukinumab.