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