JPWO2021094378A5 - - Google Patents

Description

Embodiments of the invention Embodiments of the invention are further described in the following sections:
[Section 1]
A method of treating systemic lupus erythematosus (SLE) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a type I interferon (IFN) receptor (IFNR) inhibitor. administering, wherein the IFNR inhibitor reduces SLE disease activity in the subject.
[Section 2]
2. The method of paragraph 1, wherein the ability of said IFNR inhibitor to reduce SLE disease activity in a subject has been demonstrated in a Phase III trial.
[Section 3]
Reducing SLE disease activity in the subject comprises:
a. BILAG-Based Comprehensive Lupus Assessment (BICLA) response in said subject;
b. reducing the cutaneous lupus erythematosus disease area and severity index (CLASI) score of the subject as compared to the CLASI score of the subject before treatment;
c. Reducing the number of tender joints and the number of joint swellings of the subject compared to the number of tender joints and the number of joint swellings of the subject before treatment;
d. said subject has a maximum value of 1 BILAG-2004 B score after treatment;
e. the subject has a BILAG-2004 score of C or better after treatment;
f. said subject has an improvement in at least one patient-reported outcome (PRO) compared to pre-treatment; and/or g. 2. The method of clause 1, comprising reducing the subject's SLE flare rate as compared to the subject's flare rate before treatment.
[Section 4]
4. The method according to any one of items 1 to 3 above, comprising measuring the BILAG score of the subject before and after administration of the IFNAR inhibitor.
[Section 5]
5. The method of any one of paragraphs 1-4 above, wherein the BICLA response is sustained in the subject for at least 52 weeks.
[Section 6]
6. The method of any one of paragraphs 1 to 5 above, comprising measuring PRO in the subject before and after administration of the IFNAR inhibitor.
[Section 7]
The PRO includes the subject's Functional Assessment of Chronic Illness Treatment - Fatigue (FACIT-F), Short Form 36 Health Survey Version 2 (SF-36-v2), Mental Component Summary (MCS), and/or SF-36, 7. The method of item 6 above, comprising a Physical Component Summary (PCS) score.
[Section 8]
8. The method of any one of paragraphs 1-7 above, wherein the BICLA response comprises lowering the subject's BILAG-2004 A and B domain scores to B/C/D and C/D, respectively.
[Section 9]
Clause 1 above, wherein lowering the subject's CLASI score compared to the subject's CLASI score before treatment comprises lowering the subject's CLASI-A score compared to the subject's CLASI-A score before treatment. 8. The method according to any one of items 8 to 8.
[Section 10]
10. The method of any one of paragraphs 1-9 above, wherein reducing the SLE disease activity in the subject comprises reducing anti-dsDNA levels in the subject.
[Section 11]
Reducing SLE disease activity in said subject comprises a BILAG-based comprehensive lupus assessment (BICLA) response, lowering the OCS dose administered to said subject as compared to the OCS dose administered to said subject prior to treatment. The method according to any one of the above items 1 to 10, comprising:
[Section 12]
12. The method according to item 11, wherein the OCS includes prednisone, prednisolone, and/or methylprednisolone.
[Section 13]
13. The method of any one of paragraphs 1-12 above, wherein reducing SLE disease activity in the subject comprises a BILAG-based comprehensive lupus assessment (BICLA) response by at least 4 weeks of treatment.
[Section 14]
14. The method of any one of paragraphs 1-13 above, wherein reducing SLE disease activity comprises BILAG-based comprehensive lupus assessment (BICLA) response by at least 8 weeks of treatment.
[Section 15]
Reducing SLE disease activity in said subject comprises an improvement of at least 50% in the number of tender joints and joint swelling in said subject as compared to the value of tender joint number and joint swelling number in said subject before treatment. The method according to any one of Items 1 to 14.
[Section 16]
16. The method of any one of paragraphs 1-15 above, wherein reducing SLE disease activity in the subject does not include improving Systemic Lupus Erythematosus Responder Index (SRI) 4 score.
[Section 17]
15. The method of clause 14, wherein reducing SLR disease activity in the subject does not include an improvement in Systemic Lupus Erythematosus Responder Index (SRI) 4 score after 52 weeks of treatment.
[Section 18]
18. The method of any one of paragraphs 1-17 above, wherein the reduction in the subject's CLASI score is achieved by at least 8 weeks of treatment.
[Section 19]
19. The method of any one of paragraphs 1-18 above, wherein said reduction in the subject's CLASI score is achieved after 12 weeks of treatment.
[Section 20]
20. According to any one of paragraphs 1 to 19 above, reducing SLE disease activity in the subject comprises reducing the subject's CLASI score by at least 50% compared to the subject's CLASI score before treatment. Method.
[Section 21]
21. The method of clause 20, wherein reducing SLE disease activity in the subject comprises reducing the subject's CLASI-A score after 12 weeks of treatment.
[Section 22]
22. The method according to item 20 or 21, wherein the subject has a CLASI-A score of ≧10 before treatment.
[Section 23]
23. The method of any one of paragraphs 1-22 above, wherein reducing SLE disease activity in the subject comprises having the subject have a BILAG-2004 score of C or better after 24 weeks of treatment.
[Section 24]
24. The method of any one of paragraphs 1-23 above, wherein reducing SLE disease activity in the subject comprises having a maximum value of 1 BILAG-2004 B score after 24 weeks of treatment.
[Section 25]
Paragraphs 1-24 above, wherein reducing SLE disease activity in the subject comprises reducing the BILAG-based annualized flare rate of the subject as compared to the subject's BILAG-based annualized flare rate before treatment. The method described in any one of the above.
[Section 26]
26. The method of any one of paragraphs 1-25 above, wherein reducing SLE disease activity in the subject comprises preventing flare in the subject.
[Section 27]
A flare is defined as a new BILAG-2004 A domain score of ≧1 or a new (worsening) BILAG-2004 B domain score of ≧2 compared to the subject's score one month earlier, as described in paragraphs 1-26 above. The method described in any one of the above.
[Section 28]
Reducing SLE disease activity in said subject includes reducing a flare rate in said subject as compared to a pre-treatment flare rate, and reducing SLE disease activity to said subject as compared to an OCS dose administered to said subject before treatment. 28. The method of any one of paragraphs 1-27 above, comprising lowering the OCS dose administration.
[Section 29]
29. The method of any one of paragraphs 1-28 above, comprising selecting the subject for treatment, wherein the subject is selected for suffering from active SLE.
[Section 30]
30. The method of any one of clauses 1-29 above, comprising selecting the subject for treatment, wherein the subject is selected for suffering from moderate to severe SLE.
[Section 31]
31. The method of any one of paragraphs 1-30 above, wherein the subject is selected for suffering from SLE that is unresponsive to OCS treatment.
[Section 32]
32. The method according to any one of items 1 to 31 above, wherein the subject is an adult.
[Section 33]
A method of lowering the OCS dose in a subject suffering from an autoimmune disease, the method comprising: administering to said subject a therapeutically effective amount of a type I IFN receptor inhibitor; and the OCS dose administered to said subject. and wherein the IFNR inhibitor reduces disease activity in the subject.
[Section 34]
A method of preventing OCS-related organ damage in a subject with autoimmunity, wherein the subject has received OCS prior to treatment, the subject receiving a therapeutically effective amount of a type I IFN receptor inhibitor. and lowering the OCS dose administered to the subject compared to the OCS dose administered to the subject prior to treatment, wherein the IFNR inhibitor reduces disease activity in the subject. Method.
[Section 35]
35. The method of paragraph 33 or 34, above, wherein the subject is receiving an OCS dose of ≧10 mg/day at the beginning of treatment.
[Section 36]
36. The method of any one of paragraphs 33-35 above, wherein the OCS is reduced to ≦7.5 mg/day.
[Section 37]
37. The method of paragraph 36 above, wherein the OCS dose is reduced to 0 mg/day.
[Section 38]
38. The method of any one of paragraphs 33-37 above, comprising sustaining said reduction in OCS dose for at least 12 weeks.
[Section 39]
39. The method of any one of paragraphs 33-38 above, wherein the subject has OCS-related organ damage.
[Section 40]
40. The method according to any one of items 33 to 39, wherein the OCS comprises prednisone, prednisolone, and/or methylprednisolone.
[Section 41]
41. The method according to any one of the above items 33 to 40, wherein the autoimmune disease is SLE.
[Section 42]
42. The method according to item 41, wherein the autoimmune disease is moderate to severe SLE.
[Section 43]
43. The method of paragraph 41 or 42 above, wherein the subject is selected for suffering from SLE that is unresponsive to OCS treatment.
[Section 44]
44. The method according to any one of items 1 to 43 above, wherein the type I IFN receptor inhibitor is administered intravenously.
[Section 45]
45. The method according to any one of items 1 to 44, wherein the type I IFN receptor inhibitor is an anti-type I interferon receptor antibody or an antigen-binding fragment thereof that specifically binds to IFNAR1.
[Section 46]
46. The method according to item 45, wherein the antibody is a monoclonal antibody.
[Section 47]
47. The method according to paragraph 46, wherein the antibody is anifrolumab.
[Section 48]
48. The method of paragraph 47 above, comprising administering 300 mg anifrolumab.
[Section 49]
49. The method of paragraph 47 or 48 above, wherein the anifrolumab is infused intravenously (IV) over 30 minutes.
[Section 50]
49. The method of paragraph 47 or 48 above, wherein the anifrolumab is infused IV over 30 minutes every four weeks.
[Section 51]
51. The method of any one of paragraphs 46-50 above, wherein the anifrolumab is administered from a single dose vial.
[Section 52]
52. The method of any one of paragraphs 46-51 above, wherein anifrolumab is provided in solution at a concentration of 150 mg/mL.
[Section 53]
53. The method of any one of paragraphs 46-52 above, wherein the anifrolumab is administered every 4 weeks.
[Section 54]
52. The method of any one of paragraphs 45-51 above, wherein the anifrolumab is administered for at least 52 weeks.
[Section 55]
55. A pharmaceutical composition for use in the method of treatment according to any one of items 1 to 54 above, comprising the type I IFN receptor inhibitor.
[Section 56]
56. A pharmaceutical composition for use according to item 55 above, comprising anifrolumab at a concentration of 150 mg/mL.
[Section 57]
A pharmaceutical composition for the use according to item 56 above, comprising:
a. 150mg/mL anifrolumab;
b. 50mM lysine HCl;
c. 130mM trehalose dihydrate;
d. 0.05% polysorbate 80;
e. 25mM histidine/histidine HCl
including;
A pharmaceutical composition having a pH of 5.9.
[Section 58]
55. A unit dose for use in the method according to any one of paragraphs 1 to 54 above, comprising 300 mg of anifrolumab.
[Section 59]
A kit for use in the method according to any one of items 1 to 54 above, comprising:
a. A unit dose according to item 54 above,
b. and a glass vial containing said unit dose.
[Section 60]
60. A kit for use in the method of paragraph 59 above, comprising instructions for administering said unit dose.
[Section 61]
61. The kit of clause 60, wherein the instructions state that the unit dose is administered every four weeks.
[Section 62]
62. The kit according to item 60 or 61, wherein the instructions state that the subject is suffering from moderate to severe SLE.
[Section 63]
An improved method of evaluating the effect of a treatment for SLE on patient-reported outcomes (PRO) of treatment in a subject, the method comprising: measuring a BICLA response in said subject, said BICLA response being determined by said treatment in said subject. Improved methods for improving patient-reported outcomes (PRO).
[Section 64]
The PRO includes the subject's Functional Assessment of Chronic Illness Treatment - Fatigue (FACIT-F), Short Form 36 Health Survey Version 2 (SF-36-v2), Mental Component Summary (MCS), and/or SF-36, 64. The method of paragraph 63 above, comprising a Physical Component Summary (PCS) score.
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Claims (10)

A pharmaceutical composition comprising a type I interferon (IFN) receptor (IFNR) inhibitor for the treatment of systemic lupus erythematosus (SLE) in a subject in need of treatment, the subject comprising: the pharmaceutical composition reduces SLE disease activity in the subject, and the IFNR inhibitor is
a. Human heavy chain variable region complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 3;
b. Human heavy chain variable region complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 4;
c. Human heavy chain variable region complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO: 5;
d. Human light chain variable region complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 6;
e. human light chain variable region complementarity determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO: 7; and f. Human light chain variable region complementarity determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO: 8
, wherein said subject's baseline IFNGS is measurable by a 4-gene quantitative polymerase chain reaction-based test, wherein said test comprises IFI27, IFI44, A pharmaceutical composition for measuring the expression of IFI44L and RSAD2. 2. The pharmaceutical composition of claim 1, wherein reducing SLE disease activity in the subject comprises a BILAG-based integrated lupus assessment (BICLA) response in the subject. 3. The pharmaceutical composition according to claim 1 or 2, wherein the subject is suffering from moderate to severe SLE. The antibody is
a. a human heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1; and b. A pharmaceutical composition according to any one of claims 1 to 3, comprising a human light chain variable region comprising the amino acid sequence of SEQ ID NO:2. The pharmaceutical composition according to any one of claims 1 to 4, wherein the antibody is anifrolumab or a functional variant thereof. 6. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is administered to the subject at a dose of 300 mg of the IFNR inhibitor. 7. The pharmaceutical composition of claim 5 or 6, wherein the pharmaceutical composition is administered to the subject every four weeks. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutical composition is administered intravenously to the subject. The pharmaceutical composition according to any one of claims 1 to 5, wherein the pharmaceutical composition is administered subcutaneously to the subject. A pharmaceutical composition according to any one of claims 1 to 9, wherein the subject is positive for anti-dsDNA, anti-nuclear or anti-Smith antibodies at baseline.