AstraZeneca Announces SYMBICORT Demonstrated Comparable Risk of Serious Asthma-Related Events & Lower Risk of Asthma Exacerba...
August 31 2016 - 5:00PM
Business Wire
Results of SYMBICORT LABA Safety Study in
Asthma Patients Published in The New England Journal of
Medicine
AstraZeneca today announced results from the SYMBICORT®
(budesonide/formoterol fumarate dihydrate) Inhalation Aerosol LABA
(long-acting beta2-adrenergic agonist) safety study showing
patients with controlled and uncontrolled asthma had a comparable
risk of serious asthma-related events and a lower risk of asthma
exacerbations when formoterol was combined with budesonide versus
budesonide alone.
The study compared the safety of formoterol, a LABA, used in
combination with budesonide, an inhaled corticosteroid (ICS)–the
two active therapies in SYMBICORT pressurized metered dose inhaler
(pMDI)–against budesonide (pMDI) to evaluate the risk of serious
asthma-related events. These events are defined as a composite
endpoint of asthma related events including asthma-related deaths,
intubations, and hospitalizations, with time to first serious
asthma-related event as the primary endpoint.
The results showed a comparable risk of serious asthma-related
events when formoterol was combined with budesonide versus
budesonide alone. Based on a predefined non-inferiority margin, the
upper limit of the 95% confidence interval (CI) for the hazard
ratio (HR) of the primary safety endpoint needed to be less than
two. As a result, the findings demonstrated statistical
non-inferiority of SYMBICORT to budesonide for time to first
serious asthma-related event (HR [1.073], 95% CI, [0.698-1.650]).
Furthermore, SYMBICORT therapy resulted in a 16.5% lower risk of
asthma exacerbations than budesonide (HR, 0.835; 95% CI, 0.745 to
0.937; P = 0.002).
Full study results are now available in The New England Journal
of Medicine. The study began in 2011 as a post-marketing
requirement by the U.S. Food and Drug Administration (FDA) and all
manufacturers of LABA-containing products indicated for the
treatment of asthma in the U.S. were required to conduct similar
studies evaluating the safety of LABAs when used in combination
with an ICS.
Gregory Keenan, Vice President and Head Medical Officer, US
Medical Affairs, said: “These findings reconfirm the
well-established safety profile of SYMBICORT as demonstrated in our
robust clinical program and extensive post-marketing surveillance
from around the world. We are pleased to see the importance of
ICS/LABA combination therapy in the management of asthma further
validated through this study’s findings and its publication in The
New England Journal of Medicine.”
The study was conducted at 534 centers in 25 countries and
included patients 12 years of age or older with a documented
clinical diagnosis of asthma for at least 1 year who were either
currently being treated with an inhaled corticosteroid/long-acting
β2-agonist (ICS/LABA) combination, or who had asthma that was not
adequately controlled on a long-term asthma control medication, or
whose disease severity warranted initiation of treatment with
ICS/LABA. Patients had at least one asthma exacerbation in the
previous year. In total, 11,693 patients were randomized to either
SYMBICORT pMDI (two inhalations of 80/4.5 micrograms or 160/4.5
micrograms) or budesonide pMDI (two inhalations of 80 micrograms or
160 micrograms) twice daily for 26 weeks. Forty-three patients
receiving SYMBICORT experienced 49 serious asthma-related events
and 40 patients receiving budesonide experienced 45 serious
asthma-related events. Two asthma-related deaths occurred, both in
the SYMBICORT arm; one of these patients also experienced an
asthma-related intubation. The remaining events were asthma-related
hospitalizations.
AstraZeneca has shared these results with the FDA and will soon
be discussing next steps in line with post-marketing
requirements.
INDICATIONS
SYMBICORT is indicated for the treatment of asthma in patients
12 years and older (also see Boxed WARNING).
SYMBICORT 160/4.5 is indicated for the maintenance treatment of
airflow obstruction in patients with chronic obstructive pulmonary
disease (COPD), including chronic bronchitis and emphysema.
SYMBICORT is NOT indicated for the relief of acute
bronchospasm.
IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING
- WARNING: Long-acting
beta2-adrenergic agonists (LABA), such as formoterol,
one of the active ingredients in SYMBICORT, increase the risk of
asthma-related death. A placebo-controlled study with another LABA
(salmeterol) showed an increase in asthma-related deaths in
patients receiving salmeterol. This finding with salmeterol is
considered a class effect of LABA, including formoterol. Currently
available data are inadequate to determine whether concurrent use
of inhaled corticosteroids or other long-term asthma control drugs
mitigates the increased risk of asthma-related death from
LABA. Available data from controlled clinical trials
suggest that LABA increase the risk of asthma-related
hospitalization in pediatric and adolescent patients
- When treating patients with asthma,
prescribe SYMBICORT only for patients not adequately controlled on
a long-term asthma control medication, such as an inhaled
corticosteroid or whose disease severity clearly warrants
initiation of treatment with both an inhaled corticosteroid and
LABA. Once asthma control is achieved and maintained, assess the
patient at regular intervals and step down therapy (eg, discontinue
SYMBICORT) if possible without loss of asthma control, and maintain
the patient on a long-term asthma control medication, such as an
inhaled corticosteroid. Do not use SYMBICORT for patients whose
asthma is adequately controlled on low or medium dose inhaled
corticosteroids
- SYMBICORT is NOT a rescue medication
and does NOT replace fast-acting inhalers to treat acute
symptoms
- SYMBICORT should not be initiated in
patients during rapidly deteriorating episodes of asthma or
COPD
- Patients who are receiving SYMBICORT
should not use additional formoterol or other LABA for any
reason
- Localized infections of the mouth and
pharynx with Candida albicans has occurred in patients treated with
SYMBICORT. Patients should rinse the mouth after inhalation of
SYMBICORT
- Lower respiratory tract infections,
including pneumonia, have been reported following the inhaled
administration of corticosteroids
- Due to possible immunosuppression,
potential worsening of infections could occur. A more serious or
even fatal course of chickenpox or measles can occur in susceptible
patients
- It is possible that systemic
corticosteroid effects such as hypercorticism and adrenal
suppression may occur, particularly at higher doses. Particular
care is needed for patients who are transferred from systemically
active corticosteroids to inhaled corticosteroids. Deaths due to
adrenal insufficiency have occurred in asthmatic patients during
and after transfer from systemic corticosteroids to less
systemically available inhaled corticosteroids
- Caution should be exercised when
considering administration of SYMBICORT in patients on long-term
ketoconazole and other known potent CYP3A4 inhibitors
- As with other inhaled medications,
paradoxical bronchospasm may occur with SYMBICORT
- Immediate hypersensitivity reactions
may occur, as demonstrated by cases of urticaria, angioedema, rash,
and bronchospasm
- Excessive beta-adrenergic stimulation
has been associated with central nervous system and cardiovascular
effects. SYMBICORT should be used with caution in patients with
cardiovascular disorders, especially coronary insufficiency,
cardiac arrhythmias, and hypertension
- Long-term use of orally inhaled
corticosteroids may result in a decrease in bone mineral density
(BMD). Since patients with COPD often have multiple risk factors
for reduced BMD, assessment of BMD is recommended prior to
initiating SYMBICORT and periodically thereafter
- Orally inhaled corticosteroids may
result in a reduction in growth velocity when administered to
pediatric patients
- Glaucoma, increased intraocular
pressure, and cataracts have been reported following the inhaled
administration of corticosteroids, including budesonide, a
component of SYMBICORT. Close monitoring is warranted in patients
with a change in vision or history of increased intraocular
pressure, glaucoma, or cataracts
- In rare cases, patients on inhaled
corticosteroids may present with systemic eosinophilic
conditions
- SYMBICORT should be used with caution
in patients with convulsive disorders, thyrotoxicosis, diabetes
mellitus, ketoacidosis, and in patients who are unusually
responsive to sympathomimetic amines
- Beta-adrenergic agonist medications may
produce hypokalemia and hyperglycemia in some patients
- The most common adverse reactions ≥3%
reported in asthma clinical trials included nasopharyngitis,
headache, upper respiratory tract infection, pharyngolaryngeal
pain, sinusitis, influenza, back pain, nasal congestion, stomach
discomfort, vomiting, and oral candidiasis
- The most common adverse reactions ≥3%
reported in COPD clinical trials included nasopharyngitis, oral
candidiasis, bronchitis, sinusitis, and upper respiratory tract
infection
- SYMBICORT should be administered with
caution to patients being treated with MAO inhibitors or tricyclic
antidepressants, or within 2 weeks of discontinuation of such
agents
- Beta-blockers may not only block the
pulmonary effect of beta-agonists, such as formoterol, but may
produce severe bronchospasm in patients with asthma
- ECG changes and/or hypokalemia
associated with nonpotassium-sparing diuretics may worsen with
concomitant beta-agonists. Use caution with the coadministration of
SYMBICORT
Please see full Prescribing Information, including
Boxed WARNING and Medication Guide.
NOTES TO EDITORS
About the Study
The global, multi-center study was a 26-week, randomized,
double-blind, active-controlled clinical trial comparing SYMBICORT®
(budesonide/formoterol fumarate dihydrate) Inhalation Aerosol with
budesonide HFA pressurized metered dose inhaler (pMDI). The study
evaluated the risk of serious asthma outcomes, defined as
asthma-related hospitalizations, intubation or death, in 11,693
adult and adolescent patients 12 years of age and older with
controlled and uncontrolled asthma.
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 – Respiratory and Autoimmunity, Cardiovascular
and Metabolic Diseases, and Oncology. The company is also active in
inflammation, infection and neuroscience through numerous
collaborations. 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
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