AstraZeneca Announces Study Results Show SYMBICORT Improves Lung Function in Pediatric Asthma Patients

Latest efficacy and safety findings for SYMBICORT presented at the
American College of Allergy, Asthma & Immunology 2016 Annual Scientific
Meeting

WILMINGTON, Del.–(BUSINESS WIRE)–Results from the international, multicenter ChildHood Asthma
Safety and Efficacy (CHASE) 3 Phase III study showed that
SYMBICORT® (budesonide/formoterol fumarate dihydrate)
Inhalation Aerosol 80/4.5 micrograms significantly improved lung
function in pediatric patients between 6 to <12 years of age with asthma
versus budesonide 80 micrograms, demonstrating its appropriateness as
step-up therapy in this patient population.

The CHASE 3 Phase III study evaluated the efficacy and safety of
budesonide/formoterol in a pressurized metered dose inhaler (pMDI)
80/2.25 micrograms, and SYMBICORT pMDI 80/4.5 micrograms, compared with
budesonide pMDI 80 micrograms in children with asthma, ages 6 to <12
years, who were given two inhalations twice a day for 12 weeks. The
children had previously received either medium-dose inhaled
corticosteroid (ICS) or ICS/ long-acting beta2-adrenergic
agonists (LABA). The primary efficacy endpoint was change from baseline
pre-dose (randomization) to 1-hour post-dose forced expiratory volume in
one second (FEV1) at week 12.

AstraZeneca conducted the CHASE 3 study after the US Food and Drug
Administration (FDA) requested additional data on budesonide and
formoterol, specifically regarding the impact of different doses, in
pediatric asthma patients between 6 to <12 years of age.

The study results showed changes from baseline at week 12 in 1-hour
post-dose FEV1 and 15-minute post-dose FEV1 were
significantly greater with SYMBICORT 80/4.5 micrograms two inhalations
twice daily versus budesonide 80 micrograms two inhalations twice daily
(both p≤0.015), but not budesonide/formoterol 80/2.25 micrograms two
inhalations twice daily versus budesonide 80 micrograms two inhalations
twice daily. The change from baseline in 1-hour post-dose PEF (peak
expiratory flow) was superior at week 12 with SYMBICORT 80/4.5
micrograms versus other treatments (p<0.05).

There were no notable differences in safety profiles between either of
the budesonide/formoterol doses and budesonide or between the two
budesonide/formoterol doses. Among the most common adverse events, upper
respiratory tract infection, pharyngitis, headache, and vomiting were
more frequent, with budesonide/formoterol doses compared to the
budesonide 80 micrograms dose.

The CHASE 3 results were submitted to the FDA and other health
authorities in accordance with regulatory requirements.

Gregory Keenan, Vice President, Medical Affairs and US Head Medical
Officer, said: “These safety and efficacy results from the CHASE 3 study
indicate SYMBICORT may offer an important asthma treatment option for
the appropriate pediatric populations. We look forward to working with
the regulatory authorities to help make SYMBICORT available to this
population of children with asthma.”

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 CHASE 3 Study

The global, multicenter, 12-week, randomized, double-blind,
parallel-group CHASE 3 Phase III clinical trial evaluated the efficacy
and safety of budesonide/formoterol in a pressurized metered dose
inhaler (pMDI) 80/2.25 micrograms, and SYMBICORT®
(budesonide/formoterol fumarate dihydrate) Inhalation Aerosol pMDI
80/4.5 micrograms, compared with budesonide pMDI 80 micrograms, all
given two inhalations twice-daily, in children ages 6 to <12 years with
asthma. The study randomized 279 children 6 to <12 years of age, from
which 273 received treatment, and involved a total of 88 study centers
located in four countries.

The study is part of the CHASE program made up of three pediatric
clinical studies conducted to meet Pediatric Research Equity Act (PREA)
requirements, fulfill the terms of a Complete Response Letter issued by
the US Food and Drug Administration (FDA), and respond to FDA feedback.

About Asthma

Asthma is a common, chronic condition in which inflammation and
narrowing of the airways may cause wheezing, breathlessness, chest
tightness and coughing. Despite current and available treatment options,
asthma continues to effect the health and day-to-day lifestyles of more
than 300 million children, men and women worldwide. By 2020, asthma will
likely increase in numbers to affect as many as 400 million people.

About Respiratory

Respiratory is one of AstraZeneca’s main therapy areas. Our strong
pipeline has the potential to deliver up to seven launches between 2016
and 2020. In respiratory disease, our 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. We are building on a
40-year heritage in respiratory disease, and our capability in
inhalation technology spans both pressurized metered-dose inhalers
(pMDIs) and dry powder inhalers (DPIs), as well as Co-Suspension™
Delivery Technology.

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.

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