Form 6-K ASTRAZENECA PLC For: Sep 28
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 2021
Commission
File Number: 001-11960
AstraZeneca PLC
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Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
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
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. 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
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
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.
Morand E, et al. Trial of Anifrolumab in Active
Systemic Lupus Erythematosus. N Engl J
Med. 2020;382(3):211-221.
Accessed September 2021.
2.
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.
3.
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 September 2021.
4.
Lauwerys BR, et al. Type I interferon blockade in
systemic lupus erythematosus: where do we
stand? Rheumatol. 2014;53:1369-1376. Accessed September
2021.
5.
Crow MK. Type I Interferon in the Pathogenesis of
Lupus. J Immunol. 2014;192(12):5459-5468. Accessed September
2021.
6.
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.
7.
Jefferies CA. Regulating IRFs in IFN Driven
Disease. Front
Immunol. 2019;10:325. Accessed
September 2021.
8.
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.
9.
Centers
for Disease Control and Prevention. Systemic Lupus Erythematosus
(SLE). Available online. Accessed September 2021.
10.
American College of Rheumatology. Guidelines for
referral and management of systemic lupus erythematosus in
adults. Arthritis &
Rheumatology.
1999;42:1785-1796. Accessed September 2021.
11.
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.
12.
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.
13.
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.
14.
Japan
Intractable Diseases Information Center. The number of specific
stipendiary certificate holders of medical expenses (designation
incurable disease). Available online. Accessed September
2021.
15.
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.
16.
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.
17.
The
Lupus Foundation of America. What is Lupus? Available online.
Accessed September 2021.
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.
Accessed September 2021.
19.
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.
20.
The
Lupus Foundation of America. Lupus facts and statistics. Available
online. Accessed September 2021.
21.
ClinicalTrials.gov.
Long Term Safety of Anifrolumab in Adult Subjects With Active
Systemic Lupus Erythematosus (TULIP SLE LTE). NCT Identifier:
NCT02794285. Accessed September 2021.
22.
ClinicalTrials.gov.
Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus
Erythematosus (Tulip SC). NCT Identifier: NCT04877691. Accessed
September 2021.
23.
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.
24.
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
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:
28 September 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
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