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,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 EGPA9 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
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
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References
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[Last accessed: September 2024].
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[Last accessed: September 2024].
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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.
[Last accessed: September 2024].
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Adrian Kemp
Company Secretary
AstraZeneca PLC