TIDMAZN
RNS Number : 2084H
AstraZeneca PLC
02 August 2021
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
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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 --
<ALPHA> 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
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