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 February 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Update on Saphnelo subcutaneous administration
3 February 2026
Update on US regulatory review
of Saphnelo subcutaneous administration in systemic
lupus erythematosus
The US Food and Drug Administration (FDA) issued a complete
response letter (CRL) regarding the Biologics License Application
(BLA) for Saphnelo (anifrolumab) for subcutaneous
administration in adult patients with systemic lupus erythematosus
(SLE). AstraZeneca subsequently provided the information
requested in the CRL and is committed to working with the FDA to
progress the application as quickly as
possible.
A decision from the FDA on the updated application
for Saphnelo SC is expected in the first half of 2026.
Intravenous (IV) Saphnelo remains commercially
available.
The original BLA submitted to the FDA by AstraZeneca was based on a
planned interim analysis of the Phase III TULIP-SC trial evaluating
the subcutaneous administration of Saphnelo, which met the primary endpoint. The safety
profile observed in the TULIP-SC trial was consistent with the
known clinical profile of Saphnelo administered as an intravenous (IV)
infusion.1-4
In December 2025, AstraZeneca
announced the approval
of Saphnelo in the European Union (EU) for subcutaneous
administration in adult patients with moderate to severe
SLE. Since then, the full analysis of the TULIP-SC trial also
demonstrated the subcutaneous administration
of Saphnelo met the primary endpoint of reduction in
disease activity. These results were published
in Arthritis
& Rheumatology in
January 2026.
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. To date, more than
40,000 patients globally have been treated
with Saphnelo.5
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, updated in 2025, AstraZeneca will pay BMS
a mid-teens royalty for sales in the
US.
Systemic lupus erythematosus
SLE is an autoimmune disease in which the immune system attacks
healthy tissue in the body.6 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.6-9
Over 3.4 million people globally are affected by
SLE.10 Living
with SLE can be painful, debilitating, and have a profound impact
on patients' mental and financial wellbeing.9,11-15 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.11,16 Even
a small reduction in daily steroid use (for example 1mg/day) can
lower the risk of organ damage.17
TULIP-SC
TULIP-SC was 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 aged 18 to 70 years with moderate to severe
SLE while receiving standard therapy (oral corticosteroids,
antimalarial, and/or immunosuppressants).18
The reduction of disease activity was measured using the British
Isles Lupus Assessment Group based Composite Lupus Assessment
(BICLA) at week 52.18 The
BICLA requires improvement in all organs with disease activity at
baseline with no new flares.18
Participants (367) were randomised 1:1 to receive 120mg
subcutaneous dose of anifrolumab or placebo administered via a
pre-filled, single-use syringe.18 A
planned interim analysis was conducted when the first 220
participants reached week 52.18 The
trial also includes an open-label extension period of 52 weeks for
participants who completed the 52-week treatment
period.18
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.2,19 Type
I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines
involved in regulating the inflammatory pathways implicated in
SLE.20-25
Saphnelo IV is the first
biologic with remission data in SLE from a four-year
placebo-controlled Phase III trial (TULIP-LTE) and was measured
with the DORIS criteria for remission.26,27 DORIS
is measured as clinical SLEDAI-2K, or "Systemic Lupus Erythematosus
Disease Activity Index 2000" score of 0, physician global
assessment <0.5, prednisolone/ equivalent dose of OCS dose of
≤5 mg per day and stable maintenance doses of
immunosuppressants, including biologics.28
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.29-32
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/NYSE: 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
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. AstraZeneca.
Saphnelo self-administration TULIP-SC Phase III trial meets primary
endpoint in patients with systemic lupus erythematosus based on an
interim analysis. Available at: Saphnelo
self-administration TULIP-SC Phase III trial meets primary endpoint
in patients with systemic lupus erythematosus based on an interim
analysis.
[Last accessed: February 2026].
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.
AstraZeneca data on file. 2025. REF-290598.
6. 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(9):1706-1713.
7. American College
of Rheumatology. 2025 American College of Rheumatology (ACR)
guideline for the treatment of systemic lupus erythematosus (SLE).
Available at: lupus-guideline-sle-2025.pdf.
[Last accessed: February
2026].
8. Fanouriakis A, et al. EULAR
recommendations for the management of systemic lupus erythematosus:
2023 update. Ann Rheum
Dis.
2024;83(1):15-29.
9. Kaul A, et al. Systemic lupus
erythematosus. Nat Rev Dis
Primers.
2016;2:16039.
10. Tian J, et al. Global epidemiology of
systemic lupus erythematosus: a comprehensive systematic analysis
and modelling study. Ann Rheum
Dis.
2023;82(3):351-356.
11. 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(5):e031850.
12. Primavera D, et al. Quality of Life in
Systemic Lupus Erythematosus and Other Chronic Diseases:
Highlighting the Amplified Impact of Depressive
Episodes. Healthcare. 2024;12:233. 25.
13. Liu X, et al. Mental health conditions
in patients with systemic lupus erythematosus: a systematic review
and meta-analysis. Rheumatology
(Oxford). 2024;63:3234-3242.
14. Leung J, et al. "…Not Having the
Real Support That We Need": Patients' Experiences With Ambiguity of
Systemic Lupus Erythematosus and Erosion of Social
Support. ACR Open
Rheumatol.
2019;1:135-144.
15. Elefante E, et al. Impact of disease
activity patterns on health-related quality of life (HRQoL) in
patients with systemic lupus erythematosus
(SLE). Lupus Sci
Med.
2024;11:e001202.
16. 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(12):5517-5526.
17. 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(8):998-1005.
18. Clinicaltrials.gov.
Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus
Erythematosus (Tulip SC). Available at: https://clinicaltrials.gov/study/NCT04877691.
[Last accessed: February 2026].
19. 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.
20. Lauwerys BR, et al. Type I
interferon blockade in systemic lupus erythematosus: where do we
stand? Rheumatology.
2014;53(8):1369-1376.
21. 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(11):1653-1664.
22. Jefferies CA. Regulating IRFs in IFN
driven disease. Front
Immunol.
2019;10:325.
23. Mai L, et al. The baseline
interferon signature predicts disease severity over the subsequent
years in systemic lupus erythematosus. Arthritis Res
Ther.
2021;23(1):29.
24. 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.
25. Rönnblom L, et al. Interferon
pathway in SLE: one key to unlocking the mystery of the
disease. Lupus Sci
Med.
2019;6(1):e000270.
26. Morand EF, et al. LLDAS
and remission attainment with anifrolumab treatment in patients
with systemic lupus erythematosus: results from the TULIP and
long-term extension randomised controlled
trials. Ann Rheum
Dis. 2025;
84(5): 777-778.
27. Mosca M, et al.
Attainment of LLDAS and DORIS remission during anifrolumab treatment: interim
results from a multinational, observational, post-launch study of
treatment effectiveness in the real world. Ann Rheum
Dis. 2025.
84(1):168-169.
28. Vollenhoven R, et al. 2021 DORIS
definition of remission in SLE: final recommendations from an
international task force. Lupus Science &
Medicine. 2021; 8: e000538.
doi:10.1136/ lupus-2021-000538.
29. 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: February 2026].
30. 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: February 2026].
31. Clinicaltrials.gov.
Determine Effectiveness of Anifrolumab in Systemic Sclerosis
(DAISY). Available at: https://clinicaltrials.gov/study/NCT05925803.
[Last accessed: February 2026].
32. 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: February 2026].
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.
Date: 03 February 2026
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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