a2087h
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 August 2021
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Saphnelo approved in the US for SLE
2 August 2021 07:00 BST
Saphnelo (anifrolumab) approved in the US
for
moderate to severe systemic lupus erythematosus
Saphnelo is a first-in-class type I interferon receptor antibody
and the only
new medicine in over a decade for patients with systemic lupus
erythematosus
AstraZeneca's Saphnelo (anifrolumab-fnia) has been approved in the
US for the treatment of adult patients with moderate to severe
systemic lupus erythematosus (SLE) who are receiving standard
therapy.1
The approval by the Food and Drug Administration (FDA) was based on
efficacy and safety data from the Saphnelo clinical development programme, including
two 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.1,2,3,4
This marks the first regulatory approval for a type I interferon
(type I IFN) receptor antagonist and the only new treatment
approved for SLE in more than 10 years.5,6 Type
I IFN plays a central role in the pathophysiology of lupus and
increased type I IFN signalling is associated with increased
disease activity and severity.7,8,9,10,11
Dr. Richard Furie, Chief of the Division of Rheumatology at
Northwell Health, New York, US and a principal investigator in
the Saphnelo clinical development programme, said: "Our
treatment goals in systemic lupus erythematosus are to reduce
disease activity, prevent organ damage from either the illness
itself or the medications, especially steroids, and improve one's
quality of life. Today's approval of anifrolumab represents a big
step forward for the entire lupus community. Physicians will now be
able to offer an effective new treatment that has produced
significant improvements in overall disease activity, while
reducing corticosteroid use."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "Today's landmark approval
of Saphnelo is the culmination of years of AstraZeneca's
pioneering research in the type I interferon pathway, a central
driver in systemic lupus erythematosus pathophysiology. This
ground-breaking medicine has the potential to meaningfully improve
the lives of patients living with this often debilitating
disease."
The adverse reactions that occurred more frequently in patients who
received Saphnelo in the three clinical trials included
nasopharyngitis, upper respiratory tract infection, bronchitis,
infusion-related reactions, herpes zoster and
cough.1
SLE, the most common form of lupus affecting up to 300,000 people
in the US, disproportionately affects the African-American,
Hispanic and Asian populations.12 It
is a complex autoimmune condition that can affect any organ, and
people often experience debilitating symptoms, long-term organ
damage and poor health-related quality of
life. 12,13,14,15
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.
Saphnelo is under
regulatory review for SLE in the EU and Japan. 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.
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.16 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.13 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.17,18 At
least five million people worldwide have a form of
lupus.19
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.1 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
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.20,21 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
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
IFNs.4 Type
I IFNs such as IFN-alpha, IFN-beta and IFN-kappa are cytokines
involved in regulating the inflammatory pathways implicated in
SLE.7,9,10,11,22,23 The
majority of adults with SLE have increased type I IFN signalling,
which is associated with increased disease activity and
severity.7,8
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
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. Saphnelo [anifrolumab-fnia] US prescribing
information; 2021.
2. Morand E, et al. Trial of Anifrolumab in Active Systemic Lupus
Erythematosus. N Engl J
Med. 2020;382(3):211-221.
Accessed July 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 July 2021.
4. 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.
Accessed July 2021.
5. Mahieu MA, et al. A critical review of clinical trials in
systemic lupus erythematosus. Lupus. 2016;25(10):1122-1140. Accessed July
2021.
6. Merrill JT, et al. Lupus community panel proposals for
optimising clinical trials: 2018. Lupus Sci
Med. 2018;5:e000258. Accessed
July 2021.
7. Lauwerys BR, et al. Type I interferon blockade in systemic lupus
erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376. Accessed July
2021.
8. Crow MK. Type I Interferon in the Pathogenesis of
Lupus. J Immunol. 2014;192(12):5459-5468. Accessed July
2021.
9. 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 July 2021.
10. Jefferies CA. Regulating IRFs in IFN Driven
Disease. Front
Immunol. 2019;10:325. Accessed
July 2021.
11. 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 July
2021.
12. Centers for Disease Control and Prevention. Systemic Lupus
Erythematosus (SLE). Available online. Accessed July
2021.
13. American College of Rheumatology. Guidelines for referral and
management of systemic lupus erythematosus in
adults. Arthritis &
Rheumatology.
1999;42:1785-1796. Accessed July 2021.
14. 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
July 2021.
15. 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 July 2021.
16. The Lupus Foundation of America. What is Lupus? Available
online. Accessed July 2021.
17. 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 July 2021.
18. 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 July
2021.
19. The Lupus Foundation of America. Lupus facts and statistics.
Available online. Accessed July 2021.
20. ClinicalTrials.gov. Long Term Safety of Anifrolumab in Adult
Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE).
NCT Identifier: NCT02794285. Accessed July 2021.
21. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients
With Systemic Lupus Erythematosus (Tulip SC). NCT Identifier:
NCT04877691. Accessed July 2021.
22. 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 July
2021.
23. 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 July 2021.
Adrian Kemp
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:
2 August
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|