Form 6-K ASTRAZENECA PLC For: Sep 28

September 28, 2021 6:21 AM EDT

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Washington, D.C. 20549
Report of Foreign Issuer
Pursuant to Rule 13a-16 or 15d-16 of
the Securities Exchange Act of 1934
For the month of September 2021
Commission File Number: 001-11960
AstraZeneca PLC
1 Francis Crick Avenue
Cambridge Biomedical Campus
Cambridge CB2 0AA
United Kingdom
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F X Form 40-F __
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate by check mark whether the registrant by furnishing the information contained in this Form is also thereby furnishing the information to the Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934.
Yes __ No X
If “Yes” is marked, indicate below the file number assigned to the Registrant in connection with Rule 12g3-2(b): 82-_____________
AstraZeneca PLC
Saphnelo approved in Japan for SLE
28 September 2021 07:00 BST
Saphnelo approved in Japan for 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 approved in Japan for the treatment of adult patients with systemic lupus erythematosus (SLE), a serious autoimmune disease, who show insufficient response to currently available treatment.
The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on efficacy and safety data 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, including skin and joints, and achieved sustained reduction in oral corticosteroid (OCS) use compared to placebo, with both groups receiving standard therapy.1,2,3
This decision marks the first regulatory approval by the MHLW for a type I interferon (type I IFN) receptor antagonist in Japan. Type I IFN plays a central role in the pathophysiology in lupus and increased type I IFN signalling has been shown to be associated with increased disease activity and severity.4,5,6,7,8
Dr. Yoshiya Tanaka, Professor in the First Department of Internal Medicine at the University of Occupational and Environmental Health, Kitakyushu, Japan and an investigator in the TULIP-2 trial, said: "Compared with other rheumatic diseases, there are limited treatments available for systemic lupus erythematosus and outcomes remain poor for patients in Japan and around the world. Through our own local experience with anifrolumab in clinical trials, we have observed impressive efficacy and improved patient outcomes."
Dr. Tsutomu Takeuchi, Emeritus Professor of Keio University, Tokyo, Japan and an investigator in the TULIP-2 trial, said: "Our treatment goals in systemic lupus erythematosus are to reduce disease activity, improve quality of life and prevent organ damage from either the disease or the medications used to treat it, especially corticosteroids. Innovative treatments are needed to address these goals. The anifrolumab clinical programme provided compelling evidence that blocking type I interferon is a promising new strategy in the treatment of systemic lupus erythematosus reducing both disease activity across organ systems and corticosteroid use."
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "Saphnelo is the first and only type I interferon receptor antagonist to receive approval in Japan and represents a major advance in treating systemic lupus erythematosus, a complex heterogenous disease that is challenging to treat and often debilitating for patients. We will now work to bring this medicine to patients in Japan living with this disease as quickly as possible."
The adverse reactions that occurred more frequently in patients who received Saphnelo in clinical trials included upper respiratory tract infection, bronchitis, infusion-related reactions, hypersensitivity reactions and herpes zoster.1,2,3
SLE  can affect any organ, and people often experience inadequate disease control, long-term organ damage and poor health-related quality of life.9,10,11,12 SLE is designated as an Intractable Disease in Japan through a programme that incentivises research and development of drugs to treat rare diseases that lack effective treatments, and also helps reduce cost burden on patients.13 There are approximately 60,000 registered patients with SLE in Japan, and the majority are women diagnosed before age 45.14,15
Results from the TULIP-2 Phase III trial were published in The New England Journal of Medicine, results from the TULIP-1 Phase III trial were published in The Lancet Rheumatology and results from the MUSE Phase II trial were published in Arthritis & Rheumatology. The sub-analysis of patients in Japan enrolled in TULIP-2 was presented at the Japan College of Rheumatology annual meeting in April 2021. Efficacy and safety results from the sub-analysis were consistent with the overall trial populations.16
Saphnelo is approved in the US for the treatment of moderate to severe SLE and is under regulatory review for SLE in the EU. A 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.
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.17 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.10 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.18,19 At least five million people worldwide have a form of lupus.20
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).1,2,3
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.1,2 TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy. In the trial, 362 eligible patients, including 43 patients in Japan, 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.1 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.2
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.3
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.21,22 In addition, AstraZeneca is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.
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.3 Type I IFNs such as IFN-alpha, IFN-beta and IFN-kappa are cytokines involved in regulating the inflammatory pathways implicated in SLE.4,6,7,8,23,24 The majority of adults with SLE have increased type I IFN signalling, which is associated with increased disease activity and severity.4,5
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 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 systemic lupus erythematosus), 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 (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 and follow the Company on Twitter @AstraZeneca.
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.
Morand E, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221. Accessed September 2021.
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 September 2021.
Furie R, et al. Anifrolumab, an Anti-Interferona Receptor Monoclonal Antibody, in ModeratetoSevere Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017;69(2):376-386. Accessed September 2021.
Lauwerys BR, et al. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376. Accessed September 2021.
Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol. 2014;192(12):5459-5468. Accessed September 2021.
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 September 2021.
Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol. 2019;10:325. Accessed September 2021.
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 September 2021.
Centers for Disease Control and Prevention. Systemic Lupus Erythematosus (SLE). Available online. Accessed September 2021.
American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis & Rheumatology. 1999;42:1785-1796. Accessed September 2021.
Touma Z, et al. Current and future therapies for SLE: obstacles and recommendations for the development of novel treatments. Lupus Sci Med. 2017;4:e000239. Accessed September 2021.
Izmirly PM, et al. Prevalence of Systemic Lupus Erythematosus in the United States: Estimates From a Meta-Analysis of the Centers for Disease Control and Prevention National Lupus Registries. Arthritis Rheumatol. 2021;73(6):991-996. Accessed September 2021.
Kanatani Y, et al. National Registry of Designated Intractable Diseases in Japan: Present Status and Future Prospects. Neurol Med Chir (Tokyo). 2017;57(1):1-7. Accessed September 2021.
Japan Intractable Diseases Information Center. The number of specific stipendiary certificate holders of medical expenses (designation incurable disease). Available online. Accessed September 2021.
Tanaka Y, et al. Disease severity and economic burden in Japanese patients with systemic lupus erythematosus: A retrospective, observational study. Int J Rheum Dis. 2018;21:1609-1618. Accessed September 2021.
Tanaka Y, et al. The efficacy and safety of anifrolumab in Japanese patients with systemic lupus erythematosus (SLE) (TULIP-2 subanalysis). Oral presentation at the 65th Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology; April 26-28, 2021; Kobe, Japan.
The Lupus Foundation of America. What is Lupus? Available online. Accessed September 2021.
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 September 2021.
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 September 2021.
The Lupus Foundation of America. Lupus facts and statistics. Available online. Accessed September 2021.
21. Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE). NCT Identifier: NCT02794285. Accessed September 2021.
22. Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). NCT Identifier: NCT04877691. Accessed September 2021.
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 September 2021.
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 September 2021.
Adrian Kemp
Company Secretary
AstraZeneca PLC
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
AstraZeneca PLC
Date: 28 September 2021
By: /s/ Adrian Kemp
Name: Adrian Kemp
Title: Company Secretary

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