AstraZeneca PLC Announces Positive Top-Line Data From Two Phase III SYMBICORT Studies

New findings from studies of SYMBICORT in adult patients with COPD and pediatric patients with asthma

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced positive top-line results from two international, multicenter studies in adult and pediatric patients with chronic obstructive pulmonary disease (COPD) and asthma, respectively, that showed SYMBICORT^® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol was well tolerated and achieved the primary endpoints in both studies.

“Positive results from the RISE and CHASE 3 studies reinforce SYMBICORT as an important treatment option for respiratory patients across a broad range of age groups. AstraZeneca remains committed to following the science to understand the most optimal approach for using SYMBICORT and determining the right patient type.”

The Phase IIIb Revealing the Impact of SYMBICORT in reducing Exacerbations in COPD (RISE) study compared the efficacy of SYMBICORT pressurized metered dose inhaler (pMDI) (160/4.5 micrograms) two inhalations twice-daily and formoterol Turbuhaler (4.5 micrograms) two inhalations twice-daily in reducing exacerbations in adult patients with moderate to very severe COPD. The study randomized 1,219 adults aged 40 years and older, and involved more than 200 study sites in 10 countries.

The ChildHood Asthma Safety and Efficacy (CHASE) 3 Phase III study evaluated the efficacy and safety of budesonide/formoterol in a pMDI 80/2.25 micrograms, and SYMBICORT 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.

Greg Keenan, Vice President and Head Medical Officer, US Medical Affairs, said: “Positive results from the RISE and CHASE 3 studies reinforce SYMBICORT as an important treatment option for respiratory patients across a broad range of age groups. AstraZeneca remains committed to following the science to understand the most optimal approach for using SYMBICORT and determining the right patient type.”

Full results from both studies will be shared when appropriate. CHASE 3 results will be submitted to the FDA and other health authorities in accordance with regulatory requirements, and AstraZeneca will consider additional regulatory submissions based on the full RISE study results.

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 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 COPD

COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 329 million people worldwide and is predicted to be the third leading cause of death by 2030. Improving lung function and managing daily symptoms such as breathlessness are important to the management of COPD.

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 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