[6-K] ASTRAZENECA PLC Current Report (Foreign Issuer)

Rhea-AI Filing Summary

AstraZeneca reported positive interim Phase III results from the TULIP-SC trial showing subcutaneous Saphnelo (anifrolumab) met the pre-specified primary endpoint of reduced disease activity versus placebo in patients with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE). The reduction in disease activity was measured by the BICLA at week 52, which requires improvement across organs without new flares. The interim analysis included the first 220 participants reaching week 52 from a randomised 1:1 trial of 367 participants receiving 120mg subcutaneous anifrolumab once weekly versus placebo on top of standard therapy. Safety was consistent with the known IV profile. Results are under regulatory review and slated for presentation at ACR Convergence 2025.

Positive

• Interim Phase III primary endpoint met for subcutaneous Saphnelo demonstrating statistically significant reduction in disease activity versus placebo
• Safety profile consistent with known intravenous anifrolumab experience
• Randomised placebo-controlled design with 367 participants and a pre-specified interim analysis enhances credibility
• Regulatory review ongoing and presentation planned at ACR Convergence 2025 which increases transparency

Negative

• Only interim results reported; full dataset, effect sizes, and detailed safety events not provided in this filing
• Regulatory outcome uncertain
• Financial terms noted include a low to mid-teens royalty to BMS which will affect net economics of future sales

Insights

Clinical Development Strategist

TL;DR: Interim Phase III success for SC anifrolumab supports broader patient access and may simplify administration versus IV dosing.

The TULIP-SC interim readout demonstrating a statistically significant BICLA improvement at week 52 in the first 220 evaluable patients is a materially positive development for the programme. The trial design enrolled 367 patients randomised 1:1 to 120mg weekly SC anifrolumab or placebo on background standard therapy, and the safety profile aligned with prior IV experience. These facts strengthen the clinical package for a new administration route and support ongoing regulatory interactions. Presentation at ACR Convergence 2025 will provide additional detail on effect size and subgroup analyses which are important for market positioning and label considerations.

Regulatory Affairs Analyst

TL;DR: Positive interim efficacy and consistent safety profile should aid regulatory submissions for a subcutaneous formulation.

The interim analysis meeting the primary endpoint using BICLA at week 52 provides a clear efficacy signal for SC anifrolumab. The company notes the results are under regulatory review, implying AstraZeneca may pursue label expansion or supplemental approval for the subcutaneous route. The trial's pre-specified interim nature and planned presentation at ACR suggest transparency, but full data including magnitude of benefit, safety events, and statistical boundaries will determine regulatory outcomes and potential label language.

FORM 6-K

SECURITIES AND EXCHANGE COMMISSION

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 2025 

Commission File Number: 001-11960

AstraZeneca PLC

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United Kingdom

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AstraZeneca PLC

INDEX TO EXHIBITS

1.

Saphnelo met primary endpoint in TULIP-SC

17 September 2025

Saphnelo self-administration TULIP-SC Phase III trial meets primary endpoint in patients with systemic lupus erythematosus based on an interim analysis

Subcutaneous administration of first-in-class biologic Saphnelo demonstrates statistically significant and clinically meaningful reduction in disease activity

Positive high-level results from a pre-specified interim analysis of the Phase III TULIP-SC trial in patients with systemic lupus erythematosus (SLE) showed that the subcutaneous (SC) administration of AstraZeneca's Saphnelo (anifrolumab) demonstrated a statistically significant and clinically meaningful reduction in disease activity compared to placebo.1 The  safety profile observed in the interim analysis was consistent with the known clinical profile of Saphnelo administered as an intravenous (IV) infusion.2-4

The TULIP-SC trial evaluated the efficacy and safety of the subcutaneous administration of Saphnelo compared to placebo in participants with moderately to severely active, autoantibody-positive SLE, with both treatment groups receiving standard therapy (oral corticosteroids, antimalarials, and/or immunosuppressants).5

Affecting over 3.4 million people globally, SLE can impact any organ, leading many patients to experience debilitating symptoms, irreversible organ damage and poor health-related quality of life.6-11 While oral corticosteroids are often used to provide relief from symptoms of SLE patients, they are associated with adverse events and short-term benefits without targeting the underlying drivers of the disease, preventing patients from experiencing adequate disease control and achieving remission.12-14 Recent updates to clinical guidelines elevate the importance of treating to target remission or low disease activity and minimising the use of oral corticosteroids.15,16

Susan Manzi, MD, MPH, Professor of Medicine and Chair of the Medicine Institute at Allegheny Health Network, Professor of Medicine at Drexel University College, Philadelphia and principal investigator of the TULIP-SC trial, said: "Today's results for subcutaneous anifrolumab reinforce the efficacy and safety of this therapy and provide the opportunity for this important biologic to reach a wider group of patients in a more flexible and convenient way. Despite guidelines recommending earlier intervention and biologic treatments, too many people with systemic lupus erythematosus rely on oral corticosteroids, which contribute to irreversible organ damage."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Today's news takes us one step closer in making the clinically meaningful benefits of Saphnelo accessible for more patients with systemic lupus erythematosus. The TULIP-SC results are especially important because approximately half of systemic lupus erythematosus patients today taking a biologic are already treated with a self-administered subcutaneous option. With Saphnelo, we hope to establish remission as an achievable treatment goal for more patients and we are actively working with regulatory authorities to bring this new administration option to patients as soon as possible."

The reduction in disease activity in TULIP-SC was measured using the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) at week 52.5 The BICLA requires improvement in all organs with disease activity at baseline with no new flares.5

The TULIP-SC interim results are under regulatory review and will be presented during the American College of Rheumatology (ACR) Convergence 2025 annual meeting, 24-29 October 2025. 

Saphnelo IV infusion is approved for the treatment of moderate to severe SLE in more than 70 countries worldwide including the US, EU and Japan with regulatory reviews ongoing in other countries. To date, more than 38,000 patients globally have been treated with Saphnelo.17

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.18 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.9

Over 3.4 million people globally are affected by SLE, and it is among the leading causes of death in young women in the US.7,19 Living with SLE can be painful, debilitating, have a profound impact on patients' mental and financial well-being, and disproportionately affects women in their prime, and those of Asian, Black or Hispanic racial/ ethnic backgrounds.6,7,11,20,21

An estimated 50% of people with SLE have irreversible organ damage within five years of diagnosis due to long-term corticosteroid use and disease activity.13,21,22 Even a small reduction in daily steroid use (for example 1 mg/day) can lower the risk of organ damage.23

TULIP-SC

TULIP-SC is a Phase III, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous administration of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive SLE while receiving standard therapy.5

Patients recruited were aged 18 to 70 years and must have been taking either one or any combination of the following: oral corticosteroids, antimalarial, and/or immunosuppressants. In the trial, 367 participants on standard therapy were randomised 1:1 to receive 120mg subcutaneous dose of anifrolumab or placebo administered once weekly via an accessorised prefilled syringe. A planned interim analysis was conducted when the first 220 participants reached week 52. The trial also includes an open-label extension period of 52 weeks for participants who completed the 52-week treatment period.5

Saphnelo

Saphnelo (anifrolumab) is a first-in-class, fully human monoclonal antibody that binds to subunit 1 of the type I interferon (IFN) receptor, blocking the activity of type I IFN.2,22 Type I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines involved in regulating the inflammatory pathways implicated in SLE.24-29

Saphnelo continues to be evaluated in diseases where type I IFN plays a key role, including Phase III trials in cutaneous lupus erythematosus, myositis, systemic sclerosis and lupus nephritis.30-33

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

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's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca

Contacts

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References

1.   Furie R, et al. What does it mean to be a British Isles Lupus Assessment Group-based composite lupus assessment responder? Post hoc analysis of two Phase III trials. Arthritis Rheumatol. 2021;73(11):2059-2059.

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

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

4.   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.

5.   Clinicaltrials.gov Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). Available at: https://clinicaltrials.gov/study/NCT04877691. [Last accessed: September 2025]. 

6.   Kaul A, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039.

7.   Tian J, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023;82:351-6. 

8.   Centers for Disease Control and Prevention. Systemic Lupus Erythematosus (SLE). Symptoms of lupus. Available at: https://www.cdc.gov/lupus/signs-symptoms/index.html. [Last accessed: September 2025]. 

9.   American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis & Rheumatology. 1999;42:1785-1796.

10.  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.  

11.  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. 

12.  Apostolopoulos D & Morand EF. It hasn't gone away: the problem of glucocorticoid use in lupus remains. Rheumatology (Oxford). 2017;56(Suppl 1):i114-22. 

13.  Ji L et al. Low-dose glucocorticoids should be withdrawn or continued in systemic lupus erythematosus? A systematic review and meta-analysis on risk of flare and damage accrual. Rheumatology. 2021;60:5517-26. 

14.  Lateef A & Petri M. Unmet medical needs in systemic lupus erythematosus. Arthritis Res Ther. 2012;14(Suppl 4):S4. 

15.  American College of Rheumatology. 2025 American College of Rheumatology (ACR) guideline for the treatment of systemic lupus erythematosus (SLE). Available at: https://assets.contentstack.io/v3/assets/bltee37abb6b278ab2c/bltec93920aad624e33/sle-guideline-summary-2025.pdf. [Last accessed: September 2025]. 

16.  Fanouriakis A, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024; 83: 15-29.  

17.  AstraZeneca data on file. 2025. REF-288361.

18.  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 

19.  The Rheumatologist. SLE Is a leading cause of death among women. Available at: https://www.the-rheumatologist.org/article/sle-is-a-leading-cause-of-death-among-women. [Last accessed: September 2025.]

20.  Morand EF, et al. Advances in the management of systemic lupus erythematosus. BMJ 2023;383:073980.

21.  Murimi-Worstell IB, et al. Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis. BMJ Open. 2020;10:e031850.

22.  Riggs JM, et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Sci Med. 2018;5(1):e000261

23.  Katsumata Y et al. Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study. Ann Rheum Dis. 2024;83:998-1005.

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

25.  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. 

26.  Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol. 2019;10:325.

27.  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.

28.  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.

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

30.  Clinicaltrials.gov. A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/ or Subacute Cutaneous Lupus Erythematosus (LAVENDER). Available at: https://clinicaltrials.gov/study/NCT06015737. [Last accessed: September 2025].

31.  Clinicaltrials.gov. A Study to Investigate the Efficacy and Safety of Anifrolumab Administered as Subcutaneous Injection and Added to Standard of Care Compared With Placebo Added to Standard of Care in Adult Participants With Idiopathic Inflammatory Myopathies (Polymyositis and Dermatomyositis) (JASMINE). Available at: https://clinicaltrials.gov/study/NCT06455449. [Last accessed: September 2025].

32.  Clinicaltrials.gov. Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY). Available at: https://clinicaltrials.gov/study/NCT05925803. [Last accessed: September 2025].

33.  ClinicalTrials.gov. Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis (IRIS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT05138133. [Last accessed: September 2025].

Matthew Bowden

Company Secretary

AstraZeneca PLC

SIGNATURES

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: 17 September 2025

By: /s/ Matthew Bowden

Name: Matthew Bowden

Title: Company Secretary

FAQ

What did AstraZeneca (AZNCF) announce about Saphnelo in the TULIP-SC trial?

AstraZeneca announced that a pre-specified interim analysis of the Phase III TULIP-SC trial showed subcutaneous Saphnelo met the primary endpoint of reduced disease activity versus placebo measured by BICLA at week 52.

How many patients were randomised in TULIP-SC and what was the dosing?

The trial randomised 367 participants 1:1 to receive 120mg subcutaneous anifrolumab once weekly or placebo on top of standard therapy.

What safety information did the filing provide for subcutaneous Saphnelo?

The filing states the safety profile observed in the interim analysis was consistent with the known clinical profile of Saphnelo administered as an intravenous infusion.

Are these results final and what are the next steps?

These are interim results; they are under regulatory review and AstraZeneca plans to present the data at ACR Convergence 2025.

Does AstraZeneca have commercial obligations related to Saphnelo?

Under the licensing agreement, AstraZeneca will pay a low to mid-teens royalty to Bristol-Myers Squibb (BMS) on sales, per the filing.