20 December 2021 07:00 GMT

Saphnelo recommended for approval in the EU by CHMP for the treatment of patients with systemic lupus erythematosus

Saphnelo is a first-in-class type I interferon receptor antibody shown to reduce overall disease activity in patients with systemic lupus erythematosus

AstraZeneca's Saphnelo (anifrolumab) has been recommended for marketing authorisation in the European Union (EU) as an add-on therapy for the treatment of adult patients with moderate to severe, active autoantibody-positive systemic lupus erythematosus (SLE), despite receiving standard therapy. SLE is a complex autoimmune condition that can affect any organ, and people often experience inadequate disease control, long-term organ damage and poor health-related quality of life. If approved, Saphnelo would be the first new treatment for SLE in Europe in more than a decade.¹

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the Saphnelo clinical development programme, including the TULIP Phase III trials and the MUSE Phase II trial. In these trials, more patients treated with Saphnelo experienced a reduction in overall disease activity across organ systems and achieved sustained reduction in oral corticosteroid (OCS) use compared to placebo, with both groups receiving standard therapy.^2,3,4

Ian Bruce, Professor of Rheumatology at the University of Manchester, UK, and steering committee chair for the Saphnelo SLE clinical development programme, said, "Systemic lupus erythematosus is a complex and heterogeneous disease that can have a debilitating impact on a person's quality of life. We need new treatments that are effective in reducing underlying disease activity for patients, particularly those who require higher doses of oral corticosteroids, which themselves can be damaging in the long-term. The anifrolumab clinical programme has provided compelling evidence that this medicine has the potential to be an important new option for patients."

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Saphnelo is a ground-breaking first-in-class medicine and offers physicians and patients a new way of treating systemic lupus erythematosus by targeting the type I interferon receptor, which is known to play a central role in lupus disease pathophysiology. This positive recommendation from the CHMP brings us one step closer to providing a much-needed new treatment option to improve outcomes for patients in Europe."

The adverse reactions that occurred more frequently in patients who received Saphnelo in the three clinical trials included upper respiratory tract infection, bronchitis, infusion-related reactions and herpes zoster.^2,3,4

Saphnelo was recently approved in the US, Japan and Canada for the treatment of SLE, and regulatory reviews are ongoing in additional countries. The Phase III trial in SLE using subcutaneous delivery has been initiated and additional Phase III trials are planned for lupus nephritis, cutaneous lupus erythematosus and myositis. 

Notes

Financial considerations

AstraZeneca acquired global rights to Saphnelo through an exclusive license and collaboration agreement with Medarex, Inc. in 2004. The option for Medarex to co-promote the product expired on its acquisition by Bristol-Myers Squibb (BMS) in 2009. Under the agreement, AstraZeneca will pay BMS a low to mid-teens royalty for sales dependent on geography.

Systemic lupus erythematosus

SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body.⁵ It is a chronic and complex disease with a variety of clinical manifestations that can impact many organs and can cause a range of symptoms, including pain, rashes, fatigue, swelling in joints and fevers.⁶ There are approximately 250,000 people with SLE in Europe, and most are women diagnosed between the ages of 15 and 45.^7,8 More than 50% of patients with SLE develop permanent organ damage, caused by the disease or existing treatments, which exacerbates symptoms and increases the risk of mortality.^9,10 At least five million people worldwide have a form of lupus.¹¹

TULIP-1, TULIP-2 and MUSE

All three trials for Saphnelo (TULIP-1, TULIP-2 and MUSE) were randomised, double-blinded, placebo-controlled trials in patients with moderate to severe SLE who were receiving standard therapy. Standard therapy included at least one of the following: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).^2,3,4

The pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) Phase III programme included two trials, TULIP-1 and TULIP-2, that evaluated the efficacy and safety of Saphnelo versus placebo.^2,3 TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy. In the trial, 362 eligible patients were randomised (1:1) and received a fixed-dose intravenous infusion of 300mg Saphnelo or placebo every four weeks. TULIP-2 assessed the effect of Saphnelo in reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment (BICLA) scale.² In TULIP-1, 457 eligible patients were randomised (1:2:2) and received a fixed-dose intravenous infusion of 150mg Saphnelo, 300mg Saphnelo or placebo every four weeks, in addition to standard therapy. The trial did not meet its primary endpoint based on the SLE Responder Index 4 (SRI4) composite measure.³

The MUSE Phase II trial evaluated the efficacy and safety of two doses of Saphnelo versus placebo. In MUSE, 305 adults were randomised and received a fixed-dose intravenous infusion of 300mg Saphnelo, 1,000mg Saphnelo or placebo every four weeks, in addition to standard therapy, for 48 weeks. The trial showed improvement versus placebo across multiple efficacy endpoints with both arms receiving standard therapy.⁴

Results from the TULIP-2 Phase III trial were published in The New England Journal of Medicine in January 2020, results from the TULIP-1 Phase III trial were published in The Lancet Rheumatology in December 2019 and results from the MUSE Phase II trial were published in Arthritis & Rheumatology in November 2016.

In SLE, along with the pivotal TULIP Phase III programme, Saphnelo continues to be evaluated in a long-term extension Phase III trial and a Phase III trial assessing subcutaneous delivery.^12,13 In addition, AstraZeneca is exploring the potential of Saphnelo in a variety of diseases in which type I interferon (type I IFN) plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.

Saphnelo

Saphnelo (anifrolumab) is a fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFN.⁴ Type I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines involved in regulating the inflammatory pathways implicated in SLE.^{14,15,16,17,18,19} The majority of adults with SLE have increased type I IFN signalling, which is associated with increased disease activity and severity.^14,20

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca's main disease areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by focusing on earlier biology-led treatment, eliminating preventable asthma attacks and removing COPD as a top-three leading cause of death. The Company's early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company's growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including SLE), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca's ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

Contacts

For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

References

1. European Medicines Agency. Benlysta. Available online. Accessed December 2021.

2. Morand E, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221. Accessed December 2021.

3. Furie R, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208-e219. Accessed December 2021.

4. Furie R, et al. Anifrolumab, an Anti-Interferon‐α Receptor Monoclonal Antibody, in Moderate‐to‐Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017;69(2):376-386. Accessed December 2021.

5. The Lupus Foundation of America. What is Lupus? Available online. Accessed December 2021.

6. American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheumatol. 1999;42:1785-1796. Accessed December 2021.

7. Cornet A, et al. Living with systemic lupus erythematosus in 2020: a European patient survey. Lupus Sci Med. 2021;8:e000469. Accessed December 2021.

8. Lupus Europe. FAQs. Accessed December 2021.

9. Bruce IN, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. 2015;74:1706-1713. Accessed December 2021.

10. Segura BT, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatol. 2020;59(3):524-533. Accessed December 2021.

11. The Lupus Foundation of America. Lupus facts and statistics. Available online. Accessed December 2021.

12. ClinicalTrials.gov. Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE). NCT Identifier: NCT02794285. Accessed December 2021.

13. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). NCT Identifier: NCT04877691. Accessed December 2021.

14. Lauwerys BR, et al. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376. Accessed December 2021.

15. Sarkar MK, et al. Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Ann Rheum Dis. 2018;77:1653-1664. Accessed December 2021.

16. Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol. 2019;10:325. Accessed December 2021.

17. Mai L, et al. The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther. 2021;23:29. Accessed December 2021.

18. López de Padilla CM, et al. The Type I Interferons: Basic Concepts and Clinical Relevance in Immune-mediated Inflammatory Diseases. Gene. 2016;576(101):14-21. Accessed December 2021.

19. Rönnblom L, et al. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med. 2019;6(1):e000270. Accessed December 2021.

20. Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol. 2014;192(12):5459-5468. Accessed December 2021.

Adrian Kemp

Company Secretary

AstraZeneca PLC