REG - AstraZeneca PLC - Saphnelo approved in EU for SLE

AstraZenecaAnnouncement

16/02/2022 07:00

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RNS Number : 7964B  AstraZeneca PLC  16 February 2022

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
(https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-recommended-for-eu-approval-for-sle.html)
 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
(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.( 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
(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.(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
(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.(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 (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(15) 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 (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.   Centers for Disease Control and Prevention. Systemic Lupus
Erythematosus (SLE). Available
at: https://www.cdc.gov/lupus/facts/detailed.html
(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‐α 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
(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
(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
(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
(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

 

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