REG - AstraZeneca PLC - Fasenra EGPA US FDA approval

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18/09/2024 07:00

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RNS Number : 6617E  AstraZeneca PLC  18 September 2024

 

18 September 2024

Fasenra approved in the US for 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 approved in the US for the
treatment of adult patients with eosinophilic granulomatosis with
polyangiitis (EGPA).(1) EGPA is a rare, immune-mediated vasculitis that can
result in damage to multiple organs, and without treatment, can be fatal.(2,3)

 

The approval by the US Food and Drug Administration (FDA) was based on
positive 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)
,(4) which compared the efficacy and safety of Fasenra to the only approved
EGPA treatment, mepolizumab, in patients with relapsing or refractory
EGPA.(4-6) MANDARA was the first head-to-head non-inferiority trial of
biologics in patients with EGPA.(5,7) 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.(4,5)

 

In the trial, nearly 60% of Fasenra-treated patients achieved remission which
was comparable to mepolizumab-treated patients.(4) Data also showed 41% of
Fasenra-treated patients fully tapered off oral corticosteroids (OCS) (vs. 26%
in the mepolizumab arm (difference: 16%; 95% CI: 1,31)).(4)

 

Dr. Michael Wechsler, Professor of Medicine and Director of The Asthma
Institute at National Jewish Health, and International Coordinating
Investigator of the MANDARA trial said: "This approval is great news for
patients with EGPA in the US who continue to suffer from debilitating
symptoms. Patients often rely on long-term oral corticosteroids, which can
cause serious and lasting side effects. Benralizumab is a much-needed
treatment option, with data showing that not only is remission an achievable
goal for EGPA patients, but benralizumab can also help patients taper off
steroid therapy."

 

Joyce Kullman, Executive Director, Vasculitis Foundation said: "This disease
has a devastating impact on patients and the quality of their life, and they
need more treatment options. The approval of another treatment in EGPA is
welcome news to the approximately 15,000 patients living in the US with this
difficult-to-treat rare disease."

 

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit,
AstraZeneca said: "Fasenra is already well established for the treatment of
severe eosinophilic asthma, and with this approval, physicians in the US will
now be able to offer an important new, convenient single monthly subcutaneous
injection to their 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.(4)

 

Approximately half of patients with EGPA have adult-onset severe eosinophilic
asthma (SEA) and often have sinus and nasal symptoms.(3,8,9) Fasenra is only
the second biologic approved to treat this disease.(4,5)

 

Fasenra is currently approved as an add-on maintenance treatment for 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. The FDA granted Orphan Drug Designation for Fasenra for EGPA in
2018.(14)

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.(2,3 )It is estimated that 118,000 people throughout the world
live with EGPA and approximately 15,000 patients living in the US have
EGPA.(15,16) EGPA can result in damage to multiple organs, including lungs,
upper airway, skin, heart, gastrointestinal tract and nerves.(3 )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.(3,17) Without treatment, the disease may be fatal.(3,17) Almost half
(47%) of patients do not achieve remission with current treatments.(18)

 

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.(17,19 )

 

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.(5 )In the trial, 140 patients
were randomised 1:1 to receive either a single 30mg subcutaneous injection of
Fasenra or three separate 100mg subcutaneous injections of the active
comparator every four weeks.(4)

The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.(5 )Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.(5) A secondary endpoint was the proportion of patients who were able to fully taper off OCS at weeks 48 through 52.(5 )The primary statistical analysis was to demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary endpoint.(4)

 

Fasenra
Fasenra (benralizumab) is currently approved in more than 80 countries,
including the US, EU, Japan and China.(1)(0-13) Fasenra has been prescribed
to over 130,000 patients globally.(20)

 

Fasenra is in development for other diseases including chronic obstructive
pulmonary disease, chronic rhinosinusitis with nasal polyps and
hypereosinophilic syndrome.(21-23)

 

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
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.

 

References

1.   Fasenra (benralizumab) US prescribing information; September 2024.

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

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

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

5.   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].

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

7.   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].

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

9.   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.

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 news release. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html
(https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html)
. [Last accessed: September 2024].

15.  IQVIA data on file. 2024.

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

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

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

19.  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.

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

21.  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].

22.  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].

23.  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

 

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