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US-20260125482-A1 - TREATMENT OF LUPUS

US20260125482A1US 20260125482 A1US20260125482 A1US 20260125482A1US-20260125482-A1

Abstract

The disclosure relates to methods and compositions for the treatment of systemic lupous erythematosus (SLE). Specifically, the disclosure relates to methods comprising administering to a subject a type I IFN receptor inhibitor.

Inventors

  • Catharina LINDHOLM
  • Gabriel ABREU
  • Hussein AL-MOSSAWI

Assignees

  • ASTRAZENECA AB

Dates

Publication Date
20260507
Application Date
20231012

Claims (20)

  1. 1 . A method for treating systemic lupus erythematosus (SLE) and for preventing or reducing the risk of SARS-CoV-2 infection in a subject in need thereof, the method comprising a) administering a type I IFN receptor (IFNAR1) inhibitor to the subject, and b) administering a therapeutically effective amount of a SARS-CoV-2 vaccine to the subject, wherein the method prevents or reduces the risk of SARS-CoV-2 infection in the subject following exposure of the subject to SARS-CoV-2, and wherein the method treats SLE in the subject.
  2. 2 . The method of claim 1 , wherein the IFNAR1 inhibitor is administered to the subject less than 1 month before the SARS-CoV-2 vaccine.
  3. 3 . The method of claim 1 or 2 , wherein the IFNAR1 inhibitor is administered on the same day as the SARS-CoV-2 vaccine.
  4. 4 . The method of any of preceding claim , wherein the IFNAR1 inhibitor is administered intravenously or subcutaneously.
  5. 5 . The method of any preceding claim , wherein the IFNAR1 inhibitor is administered to the subject at a dose of 120 mg to 1000 mg.
  6. 6 . The method of claim 1 , wherein the IFNAR1 inhibitor is administered to the subject intravenously at a dose of about 300 mg every 4 weeks (Q4W).
  7. 7 . The method of claim 1 , wherein the IFNAR1 inhibitor is administered to the subject intravenously at a dose of about 900 mg every 4 weeks (Q4W).
  8. 8 . The method of claim 1 , wherein the IFNAR1 inhibitor is administered to the subject subcutaneously at a dose of about 120 mg every week.
  9. 9 . A method for preventing or reducing the risk of SARS-CoV-2 infection in a subject in need thereof, wherein the subject has an autoimmune disease and has been treated with a IFNAR1 inhibitor, the method comprising administering a therapeutically effective amount of a SARS-CoV-2 vaccine to the subject, and wherein the method prevents or reduces the risk of SARS-CoV-2 infection in the subject following exposure of the subject to SARS-CoV-2.
  10. 10 . The method of claim 9 , wherein administration of the SARS-CoV-2 vaccine prevents or reduces the risk of COVID-19 pneumonia in the subject.
  11. 11 . The method of claim 9 or 10 , wherein administration of the SARS-CoV-2 vaccine prevents or reduces the risk of COVID-19 associated death in the subject.
  12. 12 . The method of any of claims 9 to 11 , wherein the SARS-CoV-2 vaccine is administered to the subject 1 month or less following administration of the IFNAR1 inhibitor to the subject.
  13. 13 . The method of any of claims 9 to 12 , wherein the IFNAR1 inhibitor was administered intravenously or subcutaneously.
  14. 14 . The method of any of claims 9 to 13 , wherein the IFNAR1 inhibitor was administered to the subject at a dose of 120 mg to 1000 mg.
  15. 15 . The method of any of claims 9 to 14 , wherein the IFNAR1 inhibitor was administered to the subject intravenously at a dose of about 300 mg every 4 weeks (Q4W).
  16. 16 . The method of any of claims 9 to 14 , wherein the IFNAR1 inhibitor was administered to the subject intravenously at a dose of about 900 mg every 4 weeks (Q4W).
  17. 17 . The method of any of claims 9 to 14 , wherein the IFNAR1 inhibitor was administered to the subject subcutaneously at a dose of about 120 mg every week.
  18. 18 . The method of any of claims 9 to 17 , comprising administering at least 2 doses of the SARS-CoV-2 vaccine to the subject.
  19. 19 . The method of claim 18 , wherein the 2 doses of the SARS-CoV-2 vaccine are administered to the subject within a period of 21 to 28 days.
  20. 20 . The method of claim 18 , wherein the 2 doses of the SARS-CoV-2 vaccine are administered to the subject within a period of 14 to 56 days.

Description

BACKGROUND Anifrolumab (MEDI-546) is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody (mAb) directed against subunit 1 of the type I interferon receptor (IFNAR1). It is composed of 2 identical light chains and 2 identical heavy chains, with an overall molecular weight of approximately 148 kDa. Anifrolumab inhibits binding of type I IFN to type I interferon receptor (IFNAR) and inhibits the biologic activity of all type I IFNs. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement that can range from mild to life-threatening disease. Given the need for long-term treatment, it is important to assess the safety and efficacy of new therapies for SLE over an extended period. However, long-term open-label studies of biologic agents have left some questions remaining because of the lack of an appropriate control comparison group [1,2]. SLE disproportionately impacts populations most severely affected by COVID-19. Individuals with SLE are often heavily immunosuppressed and have a high comorbidity burden with multiple risk factors for more severe COVID-19. The causative agent of COVID-19 is SARS-Cov-2. Although previous analyses have evaluated outcomes of infection with SARS-Cov-2 in rheumatic diseases as a group, data on individuals with SLE are limited, and it remains unclear which risk factors are associated with worse COVID-19 outcomes in this population. The effect of anifrolumab on SARS-CoV-2 infection or SARS-CoV-2 vaccination efficacy has not been assessed. Vaccination efficacy relies on stimulation of an immune response against the vaccine in the vaccinated individual. Inhibitors of type I IFN might therefore be expected to reduce SARS-CoV2 vaccination efficacy. SARS-CoV2 vaccination has been shown to be less effective in immunocompromised populations [3]. It has further been suggested that treatment with anifrolumab may increase the risk of COVID-19 related adverse events, and that SLE patients should be vaccinated against viral infection before receiving treatment with anifrolumab[4]. Treatment of patients with the biologic drug rituximab impairs the antibody response to immunization in patients with rheumatic disease for at least 6-9 months after an infusion the biologic [5]. The present invention solves one or more of the above-mentioned problems. SUMMARY The present invention relates to a method for simultaneously treating systemic lupus erythematosus (SLE) and preventing or reducing the risk of SARS-CoV-2 infection in a subject in need thereof, the method comprising administering a type I IFN receptor (IFNAR1) inhibitor to the subject, and administering a therapeutically effective amount of a SARS-CoV-2 vaccine to the subject, wherein the method prevents or reduces the risk of SARS-CoV-2 infection in the subject following exposure of the subject to SARS-CoV-2, and wherein the method treats SLE in the subject. The invention also relates to a method for preventing or reducing the risk of SARS-CoV-2 infection in a subject in need thereof, wherein the subject has an autoimmune disease and has been treated with a IFNAR1 inhibitor. The method comprises administering a therapeutically effective amount of a SARS-CoV-2 vaccine to the subject, wherein the method prevents or reduces the risk of SARS-CoV-2 infection in the subject following exposure of the subject to SARS-CoV-2. The invention also relates to a method of treating SLE in a subject in need thereof, wherein the subject has been vaccinated against COVID-19 with a SARS-CoV-2 vaccine. The method comprises administering a therapeutically effective amount of a IFNAR1 inhibitor to the subject and treats SLE in the subject. The invention also relates to pharmaceutical composition and injection devices for use in such methods. The invention is supported inter alia by data, presented herein for the first time, from a randomized, placebo-controlled phase 3 extension trial of the long-term safety and tolerability of anifrolumab in SLE (NCT02794285). The data describe the first long-term placebo-controlled study in SLE or a biologic during the global COVID-19 pandemic. The data surprisingly show that patients treated with an IFNAR1 respond to vaccination with a SARS-CoV-2 vaccine. Vaccination of patients that are on long-term treatment with an IFNAR1 is shown to effective at preventing COVID-19 infection, COVID-19 pneumonia and COVID-19 associated death in the patients. The data further surprisingly show that COVID-19 vaccination does not effect the efficacy of treatment with a IFNAR1 inhibitor in patients with SLE. BRIEF DESCRIPTION OF FIGURES FIG. 1: Patients included in the TULIP-1 or TULIP-2 trials and LTE study: treatment randomization and treatment group definitions LTE, long-term extension. aThere was an 8-week safety follow-up period. bPatients randomized to anifrolumab 150 mg were all in TULIP-1. cPatients were re-randomized to anifrolumab 300 mg or placebo for the LTE study. FIG. 2: COVID