a8051b
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 February
2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Saphnelo approved in EU for SLE
16 February 2022 07:00 GMT
Saphnelo approved in the EU for the treatment of
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) has been approved in the
European Union 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.
Saphnelo is the first
biologic for SLE approved in Europe with an indication that is not
restricted to patients with a high degree of disease activity. SLE
is a serious and complex autoimmune condition that can affect any
organ, and patients often experience inadequate disease control,
long-term organ damage and poor health-related quality of
life.1-3 There
are approximately 250,000 people with SLE in Europe, and most are
women who are diagnosed between the ages of 15 and
45.4
The approval by the European Commission was based on results from
the Saphnelo clinical development programme, including
the TULIP Phase III trials and the MUSE Phase II
trial.5-7 Across
clinical 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.5-7 Minimising
OCS use while reducing disease activity is an important treatment
goal in SLE to reduce the risk of organ damage.8,9 The
approval follows the recommendation by
the Committee for Medicinal Products for Human Use of the European
Medicines Agency in December 2021.
Ronald van Vollenhoven, Chair of Rheumatology and Director of the
Amsterdam Rheumatology Center in Amsterdam, the Netherlands said,
"In Europe, there have been limited treatment options for patients
living with systemic lupus erythematosus and many patients face
poor outcomes. Anifrolumab targets the type I interferon pathway,
which is known to play a central role in lupus pathophysiology.
Today's approval is an important step forward in treating this
disease."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Saphnelo is the first new medicine for systemic lupus
erythematosus to gain approval in Europe in over a decade and is
the only biologic not restricted to patients with a high degree of
disease activity. Saphnelo has demonstrated clinically meaningful
benefits and we look forward to bringing it to patients as quickly
as possible."
The most frequent adverse reactions that occurred in patients who
received Saphnelo in the controlled clinical trials included
upper respiratory tract infection, bronchitis, infusion-related
reactions and herpes zoster.5-7
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. 10,11
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.13 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.2 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.13,14
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.5-7 Standard
therapy included at least one of the following: OCS, antimalarials
and immunosuppressants (methotrexate, azathioprine or mycophenolate
mofetil).5-7
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.5,6 TULIP-2
demonstrated superiority across multiple efficacy endpoints versus
placebo with both arms receiving standard
therapy.5 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.5 TULIP-2
assessed the effect of Saphnelo in reducing disease activity as measured by
the BILAG-Based Composite Lupus Assessment (BICLA)
scale.5 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.6 The
trial did not meet its primary endpoint based on the SLE Responder
Index 4 (SRI4) composite measure.6
The MUSE Phase
II trial evaluated the efficacy and safety of two doses
of Saphnelo versus placebo.7 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.7 The
trial showed improvement versus placebo across multiple efficacy
endpoints with both arms receiving standard
therapy.7
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 trial15 and
a Phase III trial assessing subcutaneous
delivery.10 In
addition, AstraZeneca is exploring the potential
of Saphnelo in
a variety of diseases in which type I interferon (IFN) plays a key
role, including lupus nephritis, cutaneous lupus erythematosus and
myositis.11
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.7 Type
I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines
involved in regulating the inflammatory pathways implicated in
SLE.16-21 The
majority of adults with SLE have increased type I IFN signalling,
which is associated with increased disease activity and
severity.16,22
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. Centers for
Disease Control and Prevention. Systemic Lupus Erythematosus (SLE).
Available at: https://www.cdc.gov/lupus/facts/detailed.html [Last
accessed: February 2022]
2. American College of Rheumatology. Guidelines for
referral and management of systemic lupus erythematosus in
adults. Arthritis &
Rheumatology. 1999; 42:
1785-1796.
3. 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.
4. Cornet A, et al. Living with systemic lupus erythematosus in
2020: a European patient survey. Lupus Sci
Med. 2021; 8:
e000469.
5. Morand EF, et al. Trial of Anifrolumab in Active
Systemic Lupus Erythematosus. N Engl J
Med.
2020;382(3):211-221.
6. 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.
7. 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.
8. Al Sawah S, et al. Effect of corticosteroid use by dose on the risk
of developing organ damage over time in systemic lupus
erythematosus-the Hopkins Lupus Cohort. Lupus Sci
Med. 2015; 2 (1):
e000066.
9. Kabadi S, et al. Healthcare resource utilization and costs
associated with long-term corticosteroid exposure in patients with
systemic lupus erythematosus. Lupus. 2018; 27 (11): 1799-1809.
10. ClinicalTrials.gov.
Subcutaneous Anifrolumab in Adult
Patients With Systemic Lupus Erythematosus (Tulip SC).
Available at: https://clinicaltrials.gov/ct2/show/NCT04877691
[Last accessed: February 2022]
11. AstraZeneca
plc. Saphnelo (anifrolumab) approved in the US for
moderate to severe systemic lupus erythematosus. Available
at: https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html [Last
accessed: February 2022]
12. The
Lupus Foundation of America. What is lupus? Available
at: https://www.lupus.org/resources/what-is-lupus [Last
accessed: February 2022]
13. 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
14. 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.
15. ClinicalTrials.gov.
Long Term Safety of Anifrolumab in Adult
Subjects With Active Systemic Lupus Erythematosus (TULIP
SLE LTE). https://www.clinicaltrials.gov/ct2/show/NCT02794285 [Last
accessed: February 2022].
16. Lauwerys BR, et al. Type I interferon
blockade in systemic lupus erythematosus: where do we
stand? Rheumatol. 2014; 53:
1369-1376.
17. 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.
18. Jefferies CA. Regulating IRFs in IFN Driven
Disease. Front
Immunol. 2019; 10:
325.
19. 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.
20. 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.
21. Rönnblom L, et al. Interferon pathway in SLE: one key to unlocking
the mystery of the disease. Lupus Sci
Med. 2019; 6 (1):
e000270.
22. Crow MK. Type I Interferon in the Pathogenesis of
Lupus. J Immunol. 2014; 192 (12):
5459-5468.
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:
16 February
2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|