Treatment of suppurative hidradenitis using IL-17 antagonists

Claims

1. A method for treating hidradenitis suppurativa (HS), comprising subcutaneous (SC) administration to a patient in need thereof, of a dose of about 300 mg to about 450 mg of an antibody to IL-17 or an antigen-binding fragment thereof weekly for weeks 0, 1, 2 and 3, followed by SC at a dose of about 300 mg to about 450 mg: a) monthly (every 4 weeks), starting during week 4; or b) once every two weeks (every 2 weeks), starting during week 4; wherein the antibody to IL-17 or its antigen-binding fragment comprises i) an immunoglobulin VH domain comprising the amino acid sequence set forth in SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth in SEQ ID NO:10; ii) an immunoglobulin VH domain comprising the hypervariable regions set forth in SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or iii) an immunoglobulin VH domain comprising the hypervariable regions set forth in SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13, and an immunoglobulin VL domain comprising the hypervariable regions set forth in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and wherein the antibody to IL-17 or its antigen-binding fragment binds to an epitope of an IL-17 homodimer having two chains of the mature IL-17 protein, wherein said epitope comprises Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 in one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 in the other chain, wherein the antibody to IL-17 is characterized by a KD of approximately 100-200 pM, as measured by a biosensor system, and wherein the antibody to IL-17 is characterized by an in vivo half-life of from approximately 23 to approximately 30 days.

2. The method of claim 1, wherein the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg or about 450 mg.

3. The method according to claim 1, comprising administering an antibody to IL-17 or an antigen-binding fragment thereof to SC at a dose of approximately 300 mg weekly during weeks 0, 1, 2 and 3, and then SC at a dose of approximately 300 mg once every two weeks (every two weeks), starting during week 4.

4. The method of claim 1, comprising administering an antibody to IL-17 or an antigen-binding fragment thereof to SC at a dose of approximately 300 mg weekly during weeks 0, 1, 2 and 3, and then SC at a dose of approximately 300 mg every month (every four weeks), starting during week 4.

5. The method of any one of the preceding claims, wherein said patient achieves a sustained response after one year of treatment as measured by the inflammatory lesion count, hidradenitis suppurativa clinical response (HiSCR), numeric rating scale (NRS), modified Sartorius score for HS, hidradenitis suppurativa physician global assessment (HS-PGA), or skin disease quality of life index (DLQI).

6. The method of any one of the preceding claims, wherein said patient achieves a sustained response after one year of treatment, as measured by a simplified HiSCR (sHiSCR).

7. The method according to any one of the preceding claims, wherein prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient has previously received treatment with a systemic agent for the treatment of HS.

8. The method of claim 7, wherein the systemic agent is selected from the group consisting of a local treatment agent, an antibiotic, an immune system suppressant, a TNF-alpha inhibitor, an IL-1 antagonist, and combinations thereof.

9. The method according to any one of the preceding claims, wherein prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient has not previously received treatment with a systemic agent or a topical agent for the treatment of HS.

10. The method according to any of the preceding claims, 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.

11. The method according to any one of the preceding paragraphs, wherein the dose of the IL-17 antibody or antigen-binding fragment is approximately 300 mg.

12. The method according to any one of claims 1-2 or claims 5-10, wherein the dose of the IL-17 antibody or antigen-binding fragment is approximately 450 mg.

13. The method according to any of the preceding paragraphs, wherein the patient has moderate to severe HS.

14. The method according to any of the preceding paragraphs, wherein the patient is an adult.

15. The method according to any of the preceding paragraphs, wherein the patient is a teenager.

16. The method according to any of the preceding paragraphs, wherein the antibody to IL-17 or antigen-binding fragment is placed in a pharmaceutical composition, wherein said pharmaceutical composition further comprises a buffer and a stabilizer.

17. The method according to any of the preceding claims, wherein the pharmaceutical composition is presented in liquid form.

18. The method according to any of the preceding claims, wherein the pharmaceutical composition is presented in lyophilized form.

19. The method according to any of the preceding claims, wherein the pharmaceutical composition is placed in pre-filled syringes, vials, pens or auto-injectors.

20. The method according to any of the preceding paragraphs, wherein the dose of the antibody to IL-17 or antigen-binding fragment is approximately 300 mg, wherein the pharmaceutical composition is placed in an administration device selected from the group consisting of a pre-filled syringe, a pen syringe and an autoinjector, wherein said device is placed in a kit, and wherein said kit further contains instructions for use.

21. The method according to any of the preceding claims, wherein the dose of the IL-17 antibody or antigen-binding fragment is approximately 300 mg, wherein the pharmaceutical formulation is placed in an autoinjector or pre-filled syringe, wherein said autoinjector or pre-filled syringe is placed in a kit, and wherein said kit further comprises instructions for use.

22. The method according to any of the preceding paragraphs, wherein the dose of the antibody to IL-17 or antigen-binding fragment is approximately 300 mg, wherein the pharmaceutical composition is placed in autoinjectors or pre-filled syringes, wherein said autoinjectors or pre-filled syringes are placed in a kit, and wherein said kit further comprises instructions for use.

23. The method according to any of the preceding paragraphs, wherein the dose of the antibody to IL-17 or antigen-binding fragment is approximately 450 mg, wherein the pharmaceutical composition is placed in autoinjectors or pre-filled syringes, wherein said autoinjectors or pre-filled syringes are placed in a kit, and wherein said kit further comprises instructions for use.

24. The method according to any of the preceding claims, wherein the dose is 300 mg, and is administered by a single subcutaneous administration in a total volume of 2 ml using a formulation containing 150 mg / ml of the antibody to IL-17 or antigen-binding fragment, wherein the pharmacological effect on the patient of the antibody to IL-17 or antigen-binding fragment is equivalent to the pharmacological effect on the patient of the antibody to IL-17 or antigen-binding fragment by two separate subcutaneous administrations, each of which has a total volume of 1 ml, using the same formulation.

25. The method according to any one of claims 1 to 23, wherein the dose is 300 mg, and it is administered by two separate subcutaneous injections, each of which is 1 ml, using a formulation containing 150 mg / ml of an antibody to IL-17 or antigen-binding fragment.

26. The method according to any one of the preceding claims, wherein the IL-17 antibody or antigen-binding fragment has a Tmax of approximately 7-8 days.

27. The method of any one of the preceding claims, wherein the IL-17 antibody or antigen-binding fragment has an absolute bioavailability of from about 60% to about 80%.

28. The method according to any of the preceding claims, wherein the IL-17 antibody or antigen-binding fragment is a human monoclonal antibody.

29. The method according to any one of the preceding claims, wherein the IL-17 antibody or antigen-binding fragment is of the IgG1 / kappa isotype.

30. The method according to any of the preceding paragraphs, wherein prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient has an HS-PGA score ≥ 3.

31. The method of any one of the preceding claims, wherein prior to treatment with the IL-17 antibody or antigen-binding fragment, the patient is classified as Hurley stage II or III.

32. The method of any one of the preceding paragraphs, wherein said patient achieves a simplified HiSCR by week 16 of treatment.

33. The method of any one of the preceding paragraphs, wherein said patient achieves NRS30 by week 16 of treatment.

34. The method of any one of the preceding paragraphs, wherein said patient exhibits a reduction in HS exacerbations by week 16 of treatment.

35. The method of any one of the preceding claims, wherein said patient achieves a score reduction of ≤ 6, as measured by the DLQI, by week 16 of treatment.

36. The method of any one of the preceding claims, wherein when said method is administered to a population of patients with moderate to severe HS, at least 51% of said patients achieve a simplified HiSCR by week 16 of treatment in response to said administration step.

37. The method of any one of the preceding claims, wherein when said method is used to treat a population of patients with moderate to severe HS, at least 40% of said patients achieve a response representing an NRS30 by week 16 of treatment in response to said administration step.

38. The method of any one of the preceding claims, wherein when said method is used to treat a population of patients with moderate to severe HS, less than 15% of said patients experience an exacerbation of HS within 16 weeks of treatment in response to said administration step.

39. The method of any one of the preceding claims, wherein prior to treatment with the IL-17 antibody or antigen-binding fragment thereof, the patient did not have extensive scarring (< 20 fistulas) as a result of HS.

40. The method according to any of the preceding claims, wherein the patient is additionally treated with at least one topical preparation and at least one antiseptic in combination with an antibody to IL-17 or an antigen-binding fragment thereof.

41. The method according to any one of the preceding claims, wherein the patient is treated with an antibody to IL-17 or an antigen-binding fragment thereof for at least one year.

42. The method of any of the preceding claims, wherein the patient experiences a rapid reduction in pain, as measured by a VAS or NRS, as early as one week after the first dose of the IL-17 antibody or antigen-binding fragment thereof.

43. The method of any one of the preceding claims, wherein the patient exhibits a rapid decrease in CRP levels, as measured using a standard CRP assay, as early as one week after the first dose of the IL-17 antibody or antigen-binding fragment thereof.

44. The method of any one of the preceding claims, wherein the patient exhibits a decrease in the modified Sartorius score after 16 weeks of treatment.

45. The method of any of the preceding claims, wherein the patient demonstrates improvement according to the DLQI after 16 weeks of treatment.

46. ​​The method according to any of the preceding claims, wherein the IL-17 antibody or antigen-binding fragment is secukinumab.