Patients treated with benralizumab were more
than four times as likely to reduce oral corticosteroid (OCS) dose
than those on placebo
Benralizumab also reduced overall
exacerbation rates by 70% and exacerbations requiring emergency
room visits or hospitalizations by 93% in patients with severe,
uncontrolled eosinophilic asthma
Trial results simultaneously published in
New England Journal of Medicine
Results from the Phase III ZONDA trial presented at the American
Thoracic Society (ATS) 2017 International Congress demonstrated
that adding benralizumab to standard of care allowed patients
dependent on OCS to significantly reduce or discontinue steroids
while maintaining asthma control. Detailed results of the ZONDA
study were published today in the New England Journal of
Medicine.
The trial achieved its primary efficacy endpoint, demonstrating
statistically-significant and clinically relevant reduction in
daily maintenance OCS use with two benralizumab dosing regimens
compared with placebo. Patients treated with benralizumab were more
than four times as likely to reduce their OCS dose than those in
the placebo group. The median reduction in OCS dose was 75% for
patients treated with benralizumab versus 25% with placebo.
The ZONDA trial demonstrated significant outcomes for secondary
endpoints. For OCS reduction in the 8-week dosing regimen:
- 66% of benralizumab-treated patients
reduced OCS doses by ≥50% compared with 37% receiving placebo
- 37% of benralizumab-treated patients
reduced OCS doses by ≥90% compared with 12% receiving placebo
- 52% of benralizumab-treated patients
who were eligible to discontinue OCS per the trial protocol were
able to stop OCS use completely, compared with 19% receiving
placebo
Analysis of prevention or reduction of acute asthma events in
benralizumab-treated patients on the 8-week dosing regimen
demonstrated:
- 70% reduction in overall annual
exacerbation rate compared with placebo
- 93% reduction in exacerbations
requiring emergency room visits or hospitalizations compared with
placebo
Dr. Parameswaran Nair, Professor of Respiratory Medicine at
McMaster University in Hamilton, Canada and the lead investigator
of the trial, said: “Benralizumab showed an impressive clinical
efficacy by reducing exacerbations rate by up to 70% at the same
time enabling patients with severe asthma to significantly lower
their prednisone dose and maintain their lung function. This is
likely due to its unique mechanism of action of inhibiting the
receptor for interleukin-5 and potentially depleting blood and
airway eosinophils.”
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer, said: “One of the known
clinical characteristics of the eosinophilic asthma phenotype is an
over reliance on oral steroids to manage severe uncontrolled
disease. What is exciting about the ZONDA trial is that we have
shown benralizumab delivers a clinically meaningful OCS reduction
alongside a substantial reduction in asthma exacerbation rate
including emergency treatment or hospitalizations in this
difficult-to-treat patient population.”
The ZONDA trial evaluated the effect of benralizumab 30 mg
administered subcutaneously (SC) using either an 8- or 4-week
dosing regimen for 28 weeks in adult patients with severe,
uncontrolled eosinophilic asthma receiving high-dose inhaled
corticosteroid (ICS)/long-acting beta2 agonist (LABA) and OCS with
or without additional asthma controllers. Benralizumab was
well-tolerated, with an overall adverse event profile like that of
placebo and that observed in previous Phase III trials. The most
common adverse events (≥10%) in benralizumab-treated patients
observed in ZONDA were nasopharyngitis, worsening asthma and
bronchitis.
The data from the ZONDA trial, along with the pivotal Phase III
SIROCCO and CALIMA trials, were included in regulatory submissions
for benralizumab. Benralizumab is not approved anywhere in the
world, but is under regulatory review in the US, EU, Japan and
several other countries with a US PDUFA date in the fourth quarter
of 2017.
NOTES TO EDITORS
About Severe Asthma
Asthma affects 315 million individuals worldwide, and up to 10%
of asthma patients have severe asthma which may be uncontrolled
despite high doses of standard of care asthma controller medicines
and can require the use of chronic oral corticosteroids (OCS).
Severe uncontrolled asthma is debilitating and potentially fatal
with patients experiencing frequent exacerbations and significant
limitations on lung function and quality of life. Severe,
uncontrolled asthma has an eight times higher risk of mortality
than severe asthma.
Uncontrolled asthma can lead to a dependence on OCS, with
systemic steroid exposure potentially leading to serious and
irreversible short- and long-term adverse effects, including weight
gain, diabetes, osteoporosis, glaucoma, anxiety, depression,
cardiovascular disease and immunosuppression. There is also a
significant physical and socio-economic burden of severe asthma
with these patients accounting for 50% of asthma-related costs.
About the ZONDA Trial
ZONDA was a 28-week, randomized, double-blind, parallel-group,
placebo-controlled, multicenter Phase III trial which included 220
adult patients with severe, uncontrolled asthma requiring treatment
with high-dose ICS plus a LABA and chronic OCSs and blood
eosinophil counts of at least 150 cells/μL1. The trial assessed the
effects of benralizumab (30 mg every 4 weeks or every 8 weeks;
first three doses every 4 weeks) versus placebo on OCS dose
reduction while maintaining asthma control for adult patients with
severe asthma. The primary endpoint was the percentage change in
OCS dose from baseline to week 28.
Patients underwent randomization at week 0 to receive
benralizumab or placebo, and entered the 4-week induction phase,
during which optimized OCS doses were maintained. In the subsequent
reduction phase (weeks 4–24), OCS doses were reduced by 2.5–5.0
mg/d at 4-weekly intervals. Only patients with optimized baseline
OCS doses ≤12.5 mg/d were eligible for 100% dose reduction. See the
New England Journal of Medicine manuscript for additional
information on OCS dose protocol in the trial.
About Benralizumab
Benralizumab is an anti-eosinophil monoclonal antibody that
induces direct, and near-complete depletion of eosinophils via
antibody dependent cell-mediated cytotoxicity (ADCC). Depletion of
circulating eosinophils is rapid, with an onset of action within 24
hours as confirmed in early phase I/II trials. In the pivotal Phase
III trials, SIROCCO and CALIMA, benralizumab demonstrated
significant reduction in exacerbations and improved lung function
and asthma symptoms in severe, uncontrolled eosinophilic asthma
patients. Eosinophils are the biological effector cells that drive
inflammation and airway hyper-responsiveness in approximately 50%
of asthma patients, leading to frequent exacerbations, impaired
lung function and asthma symptoms. Benralizumab is not approved
anywhere in the world, but is under regulatory review in the US,
EU, Japan and several other countries.
Benralizumab was developed by MedImmune, AstraZeneca’s global
biologics research and development arm and is in-licensed from
BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co.,
Ltd.
About AstraZeneca in Respiratory Disease
Respiratory disease is one of AstraZeneca’s main
therapy areas, and the Company has a growing portfolio of medicines
that reached more than 18 million patients in 2016. AstraZeneca’s
aim is to transform asthma and COPD treatment through inhaled
combinations at the core of care, biologics for the unmet needs of
specific patient populations, and scientific advancements in
disease modification.
The Company is building on a 40-year heritage in respiratory
disease and AstraZeneca’s capability in inhalation technology spans
both pMDIs and dry powder inhalers, as well as the innovative
Co-SuspensionTM Delivery Technology. The company’s biologics
include benralizumab (anti-eosinophil, anti-IL-5rɑ), which has been
accepted for regulatory review in the US, EU and Japan,
tralokinumab (anti-IL-13), which is currently in Phase III, and
tezepelumab (anti-TSLP), which successfully achieved its Phase IIb
primary endpoint. AstraZeneca’s research is focused on addressing
underlying disease drivers focusing on the lung epithelium, lung
immunity and lung regeneration.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas - Oncology, Cardiovascular & Metabolic
Diseases and Respiratory. The Company also is selectively active in
the areas of Autoimmunity, Neuroscience and Infection. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit www.astrazeneca-us.com and follow us on Twitter
@AstraZenecaUS.
1 In-House Data, AstraZeneca Pharmaceuticals LP. Clinical Study
Report D3250C00020.
3340312 Last Updated 05/17
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