REG - AstraZeneca PLC - Fasenra recommended for EU approval in EGPA

AstraZenecaAnnouncement

23/09/2024 07:15

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20240923:nRSW1373Fa&default-theme=true

RNS Number : 1373F  AstraZeneca PLC  23 September 2024

23 September 2024

Fasenra recommended for approval in the EU by CHMP for the treatment of
eosinophilic granulomatosis with polyangiitis

New indication supported by the MANDARA trial which showed nearly 60% of
patients achieved remission and 41% of patients fully stopped taking oral
corticosteroids

AstraZeneca's Fasenra (benralizumab) has been recommended for approval in the
European Union (EU) as an add-on treatment for adult patients with relapsing
or refractory eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a
rare, immune-mediated vasculitis that can result in damage to multiple organs,
and without treatment, can be fatal.(1,2)( )

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency based its positive opinion on results from the MANDARA Phase
III trial published in The New England Journal of Medicine
(https://www.nejm.org/stoken/default+domain/REPRINTS_36237/full?redirectUri=/doi/full/10.1056/NEJMoa2311155)
,(3) which compared the efficacy and safety of Fasenra to the only approved
EGPA treatment, mepolizumab, in patients with relapsing or refractory
EGPA.(3-5) MANDARA was the first head-to-head non-inferiority trial of
biologics in patients with EGPA.(4,6) Patients were randomised to receive
either a single 30 mg subcutaneous injection of Fasenra, or three separate 100
mg subcutaneous injections of mepolizumab every four weeks.(3,4  )( )

 

In the trial, nearly 60% of Fasenra-treated patients achieved remission which
was comparable to mepolizumab-treated patients.(3) Data also showed 41% of
Fasenra-treated patients fully tapered off oral corticosteroids (OCS) (vs. 26%
in the comparator arm (difference: 16%; 95% CI: 1,31)).(3)( )

 

Bernhard Hellmich, Chair of the Department of Internal Medicine, Rheumatology,
and Immunology at the Medius Klinik Kirchheim, Teaching Hospital of the
University of Tübingen, Co-Director of the Vasculitis Center
Tübingen-Kirchhei, and MANDARA Principal Investigator said: "People living
with EGPA in Europe often face debilitating symptoms and suffer serious and
long-lasting side effects from treatment with long-term oral corticosteroids.
With its unique mechanism of action that leads to near complete depletion of
eosinophils, Fasenra represents a much-needed potential treatment option for
EGPA patients to help them achieve remission and taper off steroid therapy."
 

 

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit,
AstraZeneca said: "With today's recommendation, the EGPA community in Europe
is one step closer to accessing a new and convenient treatment option to
alleviate some of the impact of this debilitating disease. With over 15 years
of clinical data, Fasenra is a well-established, leading treatment for severe
eosinophilic asthma, and now has the potential to transform care for patients
with EGPA. Today's news demonstrates the potential of Fasenra to help patients
suffering from eosinophilic diseases beyond severe asthma."

 

The safety and tolerability profile for Fasenra in the MANDARA trial was
consistent with the known profile of the medicine.(3)( )

 

Approximately half of patients with EGPA have adult-onset severe eosinophilic
asthma (SEA) and often have sinus and nasal symptoms.(2,7,8) If approved,
Fasenra would be only the second biologic approved to treat this
disease.(3,4)( )

Fasenra was recently approved in the US for the treatment of EGPA(9) and is also approved as an add-on maintenance treatment for severe eosinophilic asthma (SEA) in more than 80 countries including the US, Japan, EU and China.(10-13) It is also approved in children and adolescents ages six and above in the US and Japan.(12)( )
Notes

 

Eosinophilic granulomatosis with polyangiitis
EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated
inflammatory disease that is caused by inflammation of small to medium-sized
blood vessels.(1,2 )It is estimated that 118,000 people throughout the world
live with EGPA.(14) EGPA can result in damage to multiple organs, including
lungs, upper airway, skin, heart, gastrointestinal tract and nerves.(2) The
most common symptoms and signs include extreme fatigue, weight loss, muscle
and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of
breath.(2,16) Without treatment, the disease may be fatal.(2,15) Almost half
(47%) of patients do not achieve remission with current treatments.(16)

 

There are limited treatment options for EGPA. Patients are often treated with
chronic high-dose OCS and experience recurrent relapses when attempting to
taper off OCS.(15,17 )( )

 

MANDARA
MANDARA was a Phase III, randomised, double-blinded, active-controlled trial,
which compared the efficacy and safety of Fasenra to mepolizumab in adult
patients with relapsing or refractory EGPA.(4 )In the trial, 140 patients
were randomised 1:1 to receive either a single 30 mg subcutaneous injection of
Fasenra or three separate 100 mg subcutaneous injections of the active
comparator every four weeks.(3)( )

 

The primary endpoint was the proportion of patients who were in remission at
both weeks 36 and 48.(4) Remission is defined as Birmingham Vasculitis
Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.(4) A
secondary endpoint was the proportion of patients who were able to fully taper
off OCS at weeks 48 through 52.(3) The primary statistical analysis was to
demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary
endpoint.(3)

 

Fasenra
Fasenra (benralizumab) is currently approved in more than 80 countries,
including the US, EU, Japan, and China.(10-13) Fasenra has been prescribed to
over 130,000 patients globally.(18)

 

Fasenra is in development for other diseases including chronic obstructive
pulmonary disease, chronic rhinosinusitis with nasal polyps and
hypereosinophilic syndrome.(19-21)

 

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a
wholly owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

 

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key
disease area and growth driver to the Company.

 

AstraZeneca is an established leader in respiratory care with a 50-year
heritage and a growing portfolio of medicines in immune-mediated diseases. The
Company is committed to addressing the vast unmet needs of these chronic,
often debilitating, diseases with a pipeline and portfolio of inhaled
medicines, biologics and new modalities aimed at previously unreachable
biologic targets. Our ambition is to deliver life-changing medicines that help
eliminate COPD as a leading cause of death, eliminate asthma attacks and
achieve clinical remission in immune-mediated diseases.

 

AstraZeneca (https://www.astrazeneca.com/)

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's innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://gateway.zscalertwo.net/auD?origurl=https:%2f%2fwww.linkedin.com%2fcompany%2fastrazeneca&_ordtok=Mkk3WV5DBDPmQrD4F5MGdGDMZR)

 

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.   Furuta S, et al. Update on eosinophilic granulomatosis with
polyangiitis. Allergol Int. 2019;68:430-436.

2.   American Partnership for Eosinophilic Disorders. Eosinophilic
Granulomatosis with Polyangiitis (EGPA). Available at:
https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/
(https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/) .
[Last accessed: September 2024].

3.   Wechsler ME, et al. Benralizumab versus Mepolizumab for Eosinophilic
Granulomatosis with Polyangiitis. N Engl J Med. 2024;390(10):911-921.

4.   Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA
Compared to Mepolizumab. (MANDARA). Available at:
https://classic.clinicaltrials.gov/ct2/show/NCT04157348
(https://classic.clinicaltrials.gov/ct2/show/NCT04157348) . [Last accessed:
September 2024].

5.   Mepolizumab US prescribing information. Available from:
https://www.fda.gov/files/drugs/published/125526-Mepolizumab-Clinical-PREA.pdf
(https://www.fda.gov/files/drugs/published/125526-Mepolizumab-Clinical-PREA.pdf)
[Last accessed: September 2024].

6.   AstraZeneca plc. MANDARA Phase III data published in New England
Journal of Medicine show remission is an achievable goal in eosinophilic
granulomatosis with polyangiitis (EGPA) with Fasenra. Available at:
https://www.astrazeneca.com/media-centre/medical-releases/mandara-phase-iii-data-published-new-england-journal-medicine-show-remission-achievable-goal-eosinophilic-granulomatosis-polyangiitis-egpa-fasenra.html
(https://www.astrazeneca.com/media-centre/medical-releases/mandara-phase-iii-data-published-new-england-journal-medicine-show-remission-achievable-goal-eosinophilic-granulomatosis-polyangiitis-egpa-fasenra.html)
. [Last accessed: September 2024]

7.   Cottin V, et al. Respiratory manifestations of eosinophilic
granulomatosis with polyangiitis (Churg-Strauss). Eur Respir J.
2016;48:1429-1441.

8.   Heaney L et al. Eosinophilic and Noneosinophilic Asthma: An Expert
Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe
Asthma Cohort. Chest. 2021 Sep;160(3):814-830.

9.   Fasenra (benralizumab) US prescribing information; September 2024.
Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761070s021lbl.pdf
(https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761070s021lbl.pdf)
[Last accessed: September 2024]

10.  AstraZeneca news release. Available
at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html#
(https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html)
. [Last accessed: September 2024].

11.  AstraZeneca news release. Available
at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html#
(https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html)
. [Last accessed: September 2024].

12.  AstraZeneca Annual Report 2023. Available
at: https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2023/pdf/AstraZeneca_AR_2023.pdf
(https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2023/pdf/AstraZeneca_AR_2023.pdf)
. [Last accessed: September 2024].

13.  AstraZeneca news release. Fasenra met the primary endpoint in the
MANDARA Phase III trial in eosinophilic granulomatosis with polyangiitis
(EGPA). Available
at: https://www.astrazeneca.com/media-centre/press-releases/2023/fasenra-phase-iii-egpa-trial-met-primary-endpoint.html#:~:text=Positive%20high%2Dlevel%20results%20from,EGPA)%20who%20were%20receiving%20oral
(https://www.astrazeneca.com/media-centre/press-releases/2023/fasenra-phase-iii-egpa-trial-met-primary-endpoint.html#:~:text=Positive%20high-level%20results%20from,EGPA)%20who%20were%20receiving%20oral)
. [Last accessed: September 2024].

14.  AstraZeneca Data on file. 2024. REF- 244520.

15.  Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss
Syndrome. Rheum Dis Clin N Am. 2010;36:527-543.

16.  Wechsler ME, et al. Mepolizumab or Placebo for Eosinophilic
Granulomatosis with Polyangiitis. N Engl J Med. 2017:376;1921-1932.

17.  Bell CF, et al. Burden of illness and costs associated with eosinophilic
granulomatosis with polyangiitis: evidence from a managed care database in the
United States. J Manag Care Spec Pharm. 2021;27(9):1249-1259.

18.  AstraZeneca data on file. 2024. REF-235794.

19.  Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to
Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of
Frequent Exacerbations (RESOLUTE). Available
from: https://clinicaltrials.gov/ct2/show/NCT04053634
(https://clinicaltrials.gov/ct2/show/NCT04053634) [Last accessed: September
2024].

20.  Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient
With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available
at: https://clinicaltrials.gov/ct2/show/NCT04157335
(https://clinicaltrials.gov/ct2/show/NCT04157335) [Last accessed: September
2024].

21.  Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety
of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON).
Available from: https://clinicaltrials.gov/ct2/show/NCT04191304
(https://clinicaltrials.gov/ct2/show/NCT04191304) [Last accessed: September
2024].

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCEAKNAAFLLEFA