REG - AstraZeneca PLC - Saphnelo recommended for EU approval for SLE

AstraZenecaAnnouncement

20/12/2021 07:00

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RNS Number : 1194W  AstraZeneca PLC  20 December 2021

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
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html)
, Japan
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/saphnelo-approved-in-japan-for-sle.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2018/update-on-tulip-1-phase-iii-trial-for-anifrolumab-in-systemic-lupus-erythematosus-31082018.html)
and TULIP-2
(https://www.astrazeneca.com/media-centre/press-releases/2019/anifrolumab-demonstrated-superiority-across-multiple-efficacy-endpoints-in-patients-with-systemic-lupus-erythematosus-in-phase-iii-tulip-2-trial.html)
, 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
(https://www.astrazeneca.com/media-centre/medical-releases/Arthritis-and-Rheumatology-publishes-positive-Phase-II-data-on-anifrolumab-in-lupus-14112016.html#modal-historic-confirmation)
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 (https://www.nejm.org/doi/full/10.1056/nejmoa1912196)  in
January 2020, results from the TULIP-1 Phase III trial were published in The
Lancet Rheumatology
(https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(19)30076-1/fulltext)
in December 2019 and results from the MUSE Phase II trial were published in
Arthritis & Rheumatology
(https://onlinelibrary.wiley.com/doi/full/10.1002/art.39962) 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 (http://www.astrazeneca.com) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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‐α 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

 

 

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