FASENRA enabled patients to taper off oral
corticosteroids while preventing relapses
Positive results from the MANDARA Phase III trial for FASENRA®
(benralizumab) in patients with EGPA were published in the New
England Journal of Medicine today,1 as the first head-to-head trial
of biologics in patients with EGPA,2 and the first to demonstrate
that more than half of patients achieved remission with
eosinophil-targeting biologic therapies.1 These findings were also
presented today as a late-breaking poster at the American Academy
of Allergy Asthma & Immunology (AAAAI) Annual Meeting in
Washington, DC, February 23-26.3
MANDARA compared benralizumab to mepolizumab in patients with
EGPA receiving oral corticosteroids (OCS) with or without stable
immunosuppressive therapy.2 Patients were randomized to receive
either a single 30 mg subcutaneous injection of benralizumab, or
three separate 100 mg subcutaneous injections of mepolizumab, once
every four weeks.2 Full results showed that benralizumab met the
primary endpoint of the trial and demonstrated non-inferior rates
of remission compared to mepolizumab.1 The primary endpoint of
adjusted rate of remission was 59% for benralizumab-treated
patients at weeks 36 and 48, compared with 56% for mepolizumab
(difference in rates: 3%; 95% CI:, –13,18).1 Remission in EGPA is
defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS
dose less than or equal to 4 mg/day.2
A higher proportion of FASENRA-treated patients were able to
fully taper off OCS during weeks 48 through 52 (41% in the
benralizumab arm vs. 26% in the comparator arm (difference: 16%;
95% CI: 1,31).1 Additionally, 86% of benralizumab patients vs. 74%
in the comparator arm (difference: 12%; 95% CI: −1, 25) had at
least a 50% reduction in OCS dose during weeks 48 through 52.1
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: “Patients with
EGPA typically rely on long-term, high-dose OCS, which can cause
serious and lasting side effects, and often suffer recurrent
relapses when attempting to taper off their treatment. These
findings are an exciting step forward as they affirm that
eosinophil-targeting biologic treatments helped more patients
achieve remission and taper off of steroid therapy.”
Sharon Barr, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca said, “The results from this trial are an
important step forward for the EGPA community, as this is the first
trial to demonstrate that remission from EGPA with an
eosinophil-targeting biologic is achievable for the majority of
patients. This is a significant advancement and shows that
benralizumab helped patients achieve remission and reduce chronic
OCS usage, in a convenient, single, monthly subcutaneous injection,
and could alleviate some of the impact of this debilitating
disease.”
Elevated levels of eosinophils play a central role in EGPA
disease pathophysiology.4 All patients with EGPA have very high
levels of eosinophils at some point in their disease, both in
peripheral blood and in affected tissues or organs.5,6
Approximately half of patients with EGPA have concomitant,
adult-onset severe eosinophilic asthma, and often have sinus and
nasal symptoms.5,7
FASENRA has a unique mode of action that leads to near complete
depletion of eosinophils.8,9 Treatment with benralizumab was
associated with a greater reduction of blood eosinophil counts from
week 1 compared to mepolizumab and maintained at all timepoints.1
At week 1 mean blood eosinophil count ratio to baseline was 0.15
vs. 0.39 respectively (adjusted geometric mean ratio: 0.38; 95% CI:
0.29, 0.49) and 0.10 vs. 0.26 at week 52 (adjusted geometric mean
ratio: 0.36; 95% CI: 0.27, 0.49).1 Benralizumab was well tolerated
with no new safety signals, which is consistent with the known
profile of the medicine.1
FASENRA is currently approved as an add-on maintenance treatment
for SEA in 80 countries including the US, Japan and in the EU, and
is approved for self-administration in the US, EU and other
countries.10-13
AstraZeneca has been working with regulatory authorities around
the world in order to bring benralizumab to EGPA patients as
quickly as possible.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Known hypersensitivity to benralizumab or excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Hypersensitivity
reactions (eg, anaphylaxis, angioedema, urticaria, rash) have
occurred after administration of FASENRA. These reactions generally
occur within hours of administration, but in some instances have a
delayed onset (ie, days). Discontinue in the event of a
hypersensitivity reaction.
Acute Asthma Symptoms or Deteriorating Disease
FASENRA should not be used to treat acute asthma symptoms, acute
exacerbations, or acute bronchospasm.
Reduction of Corticosteroid Dosage Do not
discontinue systemic or inhaled corticosteroids abruptly upon
initiation of therapy with FASENRA. Reductions in corticosteroid
dose, if appropriate, should be gradual and performed under the
direct supervision of a physician. Reduction in corticosteroid dose
may be associated with systemic withdrawal symptoms and/or unmask
conditions previously suppressed by systemic corticosteroid
therapy.
Parasitic (Helminth) Infection It is unknown if
FASENRA will influence a patient’s response against helminth
infections. Treat patients with pre-existing helminth infections
before initiating therapy with FASENRA. If patients become infected
while receiving FASENRA and do not respond to anti-helminth
treatment, discontinue FASENRA until infection resolves.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5%) include
headache and pharyngitis. Injection site reactions (eg, pain,
erythema, pruritus, papule) occurred at a rate of 2.2% in patients
treated with FASENRA compared with 1.9% in patients treated with
placebo.
USE IN SPECIFIC POPULATIONS
A pregnancy exposure registry monitors pregnancy outcomes in
women exposed to FASENRA during pregnancy. To enroll call
1-877-311-8972 or visit www.mothertobaby.org/fasenra.
The data on pregnancy exposure from the clinical trials are
insufficient to inform on drug-associated risk. Monoclonal
antibodies such as benralizumab are transported across the placenta
during the third trimester of pregnancy; therefore, potential
effects on a fetus are likely to be greater during the third
trimester of pregnancy.
INDICATION
FASENRA is indicated for the add-on maintenance treatment of
patients with severe asthma aged 12 years and older, and with an
eosinophilic phenotype.
- FASENRA is not indicated for treatment of other eosinophilic
conditions
- FASENRA is not indicated for the relief of acute bronchospasm
or status asthmaticus
Please read full Prescribing Information, including
Patient Information and Instructions for Use.
You may report side effects related to AstraZeneca products.
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.4,5 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.5 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.5,6 Without treatment, the
disease may be fatal.5,6 Almost half (47%) of patients do not
achieve remission with current treatments.15
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.6,16 Mepolizumab is
currently the only approved treatment for EGPA.17
MANDARA MANDARA was a randomized, double blind,
double-dummy, active-controlled, parallel group, multicentre
52-week Phase III trial which compared the efficacy and safety of
FASENRA to mepolizumab in adult patients with relapsing or
refractory EGPA.2 In the blinded trial, 140 patients were
randomized 1:1 (70 per treatment group) to receive either a single
30mg subcutaneous injection of FASENRA or three separate 100mg
subcutaneous injections of mepolizumab once every four weeks.1
The primary endpoint was the proportion of patients who were in
remission at both weeks 36 and 48.2 Remission is defined as
Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less
than or equal to 4 mg/day.2 FASENRA remission was compared to the
historical placebo rate from mepolizumab’s Phase III trial,
MIRRA.18 The primary statistical analysis was to demonstrate
non-inferiority of FASENRA versus mepolizumab based on the primary
endpoint.1
All patients who complete the 52-week double-blind treatment
period were eligible to continue into an ongoing open label
extension (OLE) period, intended to allow each patient at least one
year of treatment with open-label FASENRA.2
Mepolizumab is a humanized IL-5 antagonist monoclonal
antibody.3
FASENRA FASENRA is a monoclonal antibody that binds
directly to IL-5 receptor alpha on eosinophils and attracts natural
killer cells to induce rapid and near-complete depletion of blood
and tissue eosinophils in most patients via apoptosis (programmed
cell death).8,9
FASENRA (benralizumab) is currently approved in more than 80
countries, including the US, EU, Japan, and is approved for
self-administration in the US, EU and other countries.10-13 FASENRA
has been prescribed to over 120,000 patients globally.19
FASENRA is in development for other diseases including chronic
obstructive pulmonary disease, chronic rhinosinusitis with nasal
polyps and hypereosinophilic syndrome.20-22
FASENRA was developed by AstraZeneca and is in-licensed from
BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd.,
Japan.
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 commercialization 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 www.astrazeneca-us.com
and follow the Company on social media @AstraZeneca.
References
1. Wechsler ME, et al. Benralizumab versus Mepolizumab for
Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med.
2024. 2. Clinicaltrials.gov. Efficacy and Safety of
Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Available
at: https://classic.clinicaltrials.gov/ct2/show/NCT04157348. [Last
accessed: January 2024]. 3. Late Breaking Abstracts Presented
at Scientific Sessions 2024 AAAAI Annual Meeting February 23-26,
2024. Available at: https://www.jacionline.org/pb-assets/Health
Advance/journals/ymai/AAAAI_2024_LateBreaking_Abstracts-1707140446317.pdf.
[Last accessed: February 2024]. 4. Furuta S, et al. Update on
eosinophilic granulomatosis with polyangiitis. Allergol Int.
2019;68:430-436. 5. American Partnership for Eosinophilic
Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA).
Available at:
https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/.
[Last accessed: January 2024]. 6. Baldini C, et al. Clinical
Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis
Clin N Am. 2010;36:527–543. 7. Cottin V, et al. Respiratory
manifestations of eosinophilic granulomatosis with polyangiitis
(Churg–Strauss). Eur Respir J. 2016;48:1429-1441. 8. Kolbeck
R, et al. MEDI-563, a humanized anti-IL-5 receptor a mAb with
enhanced antibody-dependent cell-mediated cytotoxicity function. J
Allergy Clin Immunol. 2010;125:1344-1353.e2. 9. Pham TH, et
al. Reductions in eosinophil biomarkers by benralizumab in patients
with asthma. Respir Med. 2016;111:21-29. 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.
[Last accessed: January 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.
[Last accessed: January 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.
[Last accessed: February 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.
[Last accessed: February 2024]. 14. AstraZeneca Data on file.
2022. REF-167820. 15. Wechsler ME, et al. Mepolizumab or
Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J
Med. 2017:376;1921-1932. 16. 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. 17.
Mepolizumab US prescribing information. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125526Orig1s021,761122Orig1s011Corrected_lbl.pdf
[Last accessed: January 2024]. 18. AstraZeneca Data on file.
2023. REF-196096. 19. AstraZeneca Data on File. 2022.
REF-153839 20. 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. [Last accessed:
September 2023]. 21. 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. [Last accessed:
January 2024]. 22. 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. [Last accessed:
January 2024].
Veeva ID: Z4-61457 Date
of Preparation: Feb 2024
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