Integrated analysis of a large cohort of continuously treated
patients to be presented at American Thoracic Society 2019 International
Conference
A new integrated analysis of Phase III data for FASENRA®
(benralizumab) shows that patients with severe eosinophilic asthma who
were continuously treated with the medicine for up to two years reduced
their use of oral corticosteroids (OCS) and experienced a sustained
improvement in exacerbation rates, lung function, asthma control and
health-related quality of life.
The analysis, presented today at the American Thoracic Society (ATS)
2019 International Conference, provides long-term efficacy and safety
data for FASENRA from the one-year Phase III SIROCCO and CALIMA
exacerbation trials, the one-year Phase III BORA extension trial and the
28-week Phase III ZONDA OCS-sparing trial.
The integrated analysis includes 1,161 FASENRA patients, of whom 1,030
are in the SIROCCO/CALIMA/BORA full analysis set and 131 are in the
ZONDA/BORA analysis set.
In the integrated analysis of ZONDA and BORA, 75% of patients had at
least a 50% reduction in their OCS dosages from baseline after 84 weeks
of FASENRA treatment every eight weeks, and 39% of patients had at least
a 90% reduction. OCS dosage was reduced by 67% by the end of the
integrated study period, which was similar to reductions seen in the
ZONDA trial of 75% from baseline compared with 25% for placebo. FASENRA
is not approved for the treatment of other eosinophilic conditions or
relief of acute bronchospasm or status asthmaticus.
Colin Reisner, Senior Vice President and Head of Late RIA, R&D
BioPharmaceuticals, said: “These new data strengthen FASENRA’s clinical
profile and are an important confirmation of its long-term efficacy and
safety profile in severe eosinophilic asthma, which is a debilitating,
chronic disease.”
J. Mark FitzGerald, MD, Director of the Centre for Heart and Lung Health
at the Vancouver Coastal Health Research Institute, and lead
investigator, said: “Long-term efficacy and safety data as shown in this
FASENRA integrated analysis are important to physicians treating severe
asthma. The results can also give confidence to physicians that their
ability to reduce patients’ oral corticosteroid use can be maintained
long term, a key treatment goal given the potential for significant
adverse effects.”
The integrated analysis demonstrated that the improvements in
exacerbation rate, lung function, asthma control and health-related
quality of life observed in the SIROCCO/CALIMA trials during the initial
one-year treatment period were maintained in continuously treated
patients over the two-year integrated treatment period.
The safety profile in the integrated analysis was similar to that
observed in the SIROCCO, CALIMA, ZONDA and BORA trials, with no increase
in the frequencies of overall or serious adverse events. The three most
common adverse events reported for those SIROCCO or CALIMA patients who
received FASENRA and entered BORA were viral upper respiratory
infection, upper respiratory tract infection and bronchitis.
FASENRA is AstraZeneca's first respiratory biologic and is currently
approved as an add-on maintenance treatment for severe eosinophilic
asthma in the US, EU, Japan and several other countries.
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
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.
You may report side effects related to AstraZeneca products by
clicking here.
NOTES TO EDITORS
About the integrated efficacy and safety analysis
The analysis was conducted to integrate FASENRA efficacy and safety data
from the adult completion phase of the BORA long-term extension trial
with data from SIROCCO or CALIMA and ZONDA trials.
These analyses include results for 1,161 patients from the three
placebo-controlled trials, SIROCCO (48 weeks), CALIMA (56 weeks) and
ZONDA (28 weeks), who received FASENRA 30 mg either every 4 weeks (Q4W)
or every 8 weeks (Q8W; first three doses Q4W) throughout the respective
Phase III trial and one year of BORA. Patients who received placebo in
the predecessor trials were excluded from analysis. Analyzed patients
had blood eosinophil counts of 300 cells/μL or greater (SIROCCO/CALIMA)
or of 150 cells/μL or greater (ZONDA) at baseline.
Results from the one-year BORA extension trial of patients who had
completed SIROCCO or CALIMA (patients who received FASENRA or placebo)
were published in The Lancet Respiratory Medicine in
November 2018.
About severe asthma
Asthma affects approximately 26.5 million individuals in the US. 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 a higher
risk of mortality than severe asthma.
Severe, uncontrolled asthma can lead to a dependence on OCS, with
systemic steroid exposure potentially leading to serious 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
socioeconomic burden of severe, uncontrolled asthma with these patients
accounting for 50% of asthma-related costs despite comprising only 10%
of the asthma population.
Clinical features associated with an eosinophilic phenotype that can act
as markers for enhanced efficacy with targeted therapy in severe
eosinophilic asthma include: greater baseline blood eosinophil counts, a
history of more frequent exacerbations, chronic OCS use and a history of
nasal polyposis.
About FASENRA
FASENRA is a monoclonal antibody that binds directly to the IL-5α
receptor on eosinophils, and attracts natural killer cells to induce
rapid and near-complete depletion of eosinophils via apoptosis
(programmed cell death). Eosinophils are a type of white blood cell that
are a normal part of the body's immune system and elevated levels of
eosinophils are seen in about half of severe asthma patients. Elevated
levels of eosinophils impact airway inflammation and airway
hyperresponsiveness, resulting in increased asthma severity and
symptoms, decreased lung function and increased risk of exacerbations.
FASENRA is AstraZeneca’s first respiratory biologic, now approved as an
add-on maintenance treatment in severe eosinophilic asthma in the US,
EU, Japan, and several other countries, and under regulatory review in
several other jurisdictions. Where approved, FASENRA is available
as a fixed-dose subcutaneous injection via a prefilled syringe
administered once every 4 weeks for the first 3 doses, and then once
every 8 weeks thereafter.
FASENRA was developed by AstraZeneca and is in-licensed from BioWa,
Inc., a wholly owned subsidiary of Kyowa Hakko Kirin Co., Ltd., Japan.
About AstraZeneca in respiratory diseases
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 2018. AstraZeneca’s aim is to transform asthma and
chronic obstructive pulmonary disease (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 pressurized
metered-dose inhalers and dry powder inhalers, as well as the
AEROSPHERE™ Delivery Technology. The Company has a growing portfolio of
respiratory biologics including benralizumab (anti-IL-5rɑ), which is
also in development for severe nasal polyposis and other eosinophilic
conditions, and has been granted Orphan Drug Designation by the US Food
and Drug Administration for eosinophilic granulomatosis with
polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Tezepelumab
(anti-TSLP) has also been granted Breakthrough Therapy Designation in
patients with severe asthma and is in Phase III trials. 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
therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. 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.
US-29511 Last Updated 5/19
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