a1226w
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 December 2021
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.
Saphnelo
recommended for EU approval for SLE
20 December 2021 07:00 GMT
Saphnelo recommended for approval in the EU by CHMP
for the treatment of patients with 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 recommended for
marketing authorisation in the European Union (EU) as an add-on
therapy for the treatment of adult patients with moderate to
severe, active autoantibody-positive systemic lupus erythematosus
(SLE), despite receiving standard therapy. SLE is a complex
autoimmune condition that can affect any organ, and people often
experience inadequate disease control, long-term organ damage and
poor health-related quality of life. If
approved, Saphnelo would be the first new treatment for SLE in
Europe in more than a decade.1
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on results
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 and achieved sustained reduction in
oral corticosteroid (OCS) use compared to placebo, with both groups
receiving standard therapy.2,3,4
Ian Bruce, Professor of Rheumatology at the University of
Manchester, UK, and steering committee chair for
the Saphnelo SLE clinical development programme, said,
"Systemic lupus erythematosus is a complex and heterogeneous
disease that can have a debilitating impact on a person's quality
of life. We need new treatments that are effective in reducing
underlying disease activity for patients, particularly those who
require higher doses of oral corticosteroids, which themselves can
be damaging in the long-term. The anifrolumab clinical programme
has provided compelling evidence that this medicine has the
potential to be an important new option for
patients."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Saphnelo is a ground-breaking first-in-class medicine
and offers physicians and patients a new way of treating systemic
lupus erythematosus by targeting the type I interferon receptor,
which is known to play a central role in lupus disease
pathophysiology. This positive recommendation from the CHMP brings
us one step closer to providing a much-needed new treatment option
to improve outcomes for patients in Europe."
The adverse reactions that occurred more frequently in patients who
received Saphnelo in the three clinical trials included upper
respiratory tract infection, bronchitis, infusion-related reactions
and herpes zoster.2,3,4
Saphnelo was
recently approved in the US, Japan and
Canada for the treatment of SLE, and regulatory reviews are ongoing
in additional countries. 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.
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.5 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 There
are approximately 250,000 people with SLE in Europe, and most are
women diagnosed between the ages of 15 and 45.7,8 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.9,10 At
least five million people worldwide have a form of
lupus.11
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).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
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.
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.12,13 In
addition, AstraZeneca is exploring the potential
of Saphnelo in a variety of diseases in which type I
interferon (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.4 Type
I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines
involved in regulating the inflammatory pathways implicated in
SLE.14,15,16,17,18,19 The
majority of adults with SLE have increased type I IFN signalling,
which is associated with increased disease activity and
severity.14,20
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 chronic obstructive pulmonary disease (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 SLE), 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. European Medicines Agency. Benlysta. Available online. Accessed
December 2021.
2. Morand E, et al. Trial of Anifrolumab in Active Systemic Lupus
Erythematosus. N Engl J
Med. 2020;382(3):211-221.
Accessed December 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 December 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 December 2021.
5. The Lupus Foundation of America. What is Lupus? Available
online. Accessed December 2021.
6. American College of Rheumatology. Guidelines for referral and
management of systemic lupus erythematosus in
adults. Arthritis
Rheumatol. 1999;42:1785-1796.
Accessed December 2021.
7. Cornet A, et al. Living with systemic lupus erythematosus
in 2020: a European patient survey. Lupus Sci
Med. 2021;8:e000469. Accessed
December 2021.
8. Lupus Europe. FAQs. Accessed December 2021.
9. 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 December 2021.
10. 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 December
2021.
11. The Lupus Foundation of America. Lupus facts and statistics.
Available online. Accessed December 2021.
12. ClinicalTrials.gov. Long Term Safety of Anifrolumab in Adult
Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE).
NCT Identifier: NCT02794285. Accessed December 2021.
13. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients
With Systemic Lupus Erythematosus (Tulip SC). NCT Identifier:
NCT04877691. Accessed December 2021.
14. Lauwerys BR, et al. Type I interferon blockade in systemic
lupus erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376. Accessed December
2021.
15. 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 December 2021.
16. Jefferies CA. Regulating IRFs in IFN Driven
Disease. Front
Immunol. 2019;10:325. Accessed
December 2021.
17. 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
December 2021.
18. 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 December
2021.
19. 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 December 2021.
20. Crow MK. Type I Interferon in the Pathogenesis of
Lupus. J Immunol. 2014;192(12):5459-5468. Accessed December
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:
20 December 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|