AstraZeneca submits sNDA for SYMBICORT in chronic obstructive pulmonary disease

AstraZeneca today announced that it submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for approval of a new indication for SYMBICORT (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol for the treatment of patients with Chronic Obstructive Pulmonary Disease (COPD). SYMBICORT is currently approved for the long-term maintenance treatment of asthma in patients 12 years and older.

"COPD is a serious, debilitating lung disease affecting 12 million Americans,¹" said lead investigator Dr. Donald Tashkin of the University of California, Los Angeles (UCLA). "If SYMBICORT receives approval from the FDA to help manage COPD, it could offer the millions of people living with this disease a new treatment option."

The sNDA submission is based on results from two pivotal efficacy and safety trials, SHINE and SUN, with SYMBICORT pressurized metered dose inhaler (pMDI).^{2, 3} Of note, both trials showed a safety profile consistent with the established profiles for this product and its mono-components.^{2, 3} The most common adverse events found in these trials were bronchitis, oral candidiasis, viral upper respiratory tract infection and nasopharyngitis, also known as the common cold.^{2, 3}

 SHINE Study Results

• 6-month randomized, double-blind, parallel-group, multi-center trial of patients (N=1,704) with moderate to very severe COPD.³
• SYMBICORT 160/4.5 micrograms (mcg) two puffs twice a day demonstrated a statistically significantly greater increase from baseline in average pre-dose FEV₁ compared with formoterol 4.5 and in average post-dose FEV₁ compared with budesonide 160, with maintenance of effect for both comparisons over the 6-month treatment period.³
• SYMBICORT pMDI 160/4.5 also demonstrated a significant increase from baseline for the average post-dose FEV₁ compared with formoterol 4.5.³

SUN Study Results

• 12-month randomized, double-blind, parallel-group, multi-center trial of patients (N=1,964) with moderate to very severe COPD.²
• SYMBICORT 160/4.5 mcg two puffs twice a day (320/9 mcg) met the pre-specified co-primary endpoints.²
• SYMBICORT demonstrated a statistically significantly greater increase from baseline in pre-dose FEV₁ and 1-hour post-dose FEV₁ compared with formoterol and placebo.²
• Results showed an overall maintenance effect over the 12-month treatment period in patients with moderate to very severe COPD.²

  "SYMBICORT is a combination maintenance treatment for patients with asthma that works rapidly to help improve lung function by reducing inflammation in the lining of the lung, ^{4, 8}" said Howard Hutchison, Chief Medical Officer, AstraZeneca. "We are confident in the data from the SHINE and SUN trials that support our submission, and we look forward to discussions with the FDA about this potential expanded indication."

 About COPD

More than 12 million people in the United States suffer from COPD, and it is the fourth leading cause of death in the nation.¹ Some estimates also suggest that 12 million more people have COPD but are undiagnosed.¹ COPD is a term referring to two serious lung diseases - emphysema and chronic bronchitis - that cause a person's airways to become inflamed over time, making it difficult to breathe normally.¹ Common symptoms include shortness of breath, chronic cough, wheezing and excess mucus.¹ For patients with moderate to very severe COPD, to reduce exacerbations and improve lung function and health status, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends the use of combination treatments with an inhaled corticosteroid (ICS) and long-acting beta₂-agonist (LABA), in addition to other treatment options.⁶ COPD is a progressive disease, which means people with COPD can expect lung function to worsen over time.⁶ When symptoms are severe, it can be difficult for a person to perform simple, daily tasks.¹ As the disease progresses, people with COPD may eventually require supplemental oxygen and may have to rely on mechanical ventilatory assistance.⁷

About SYMBICORT

SYMBICORT is a combination therapy indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older.⁴ Administered twice daily, SYMBICORT is a combination of two proven asthma medications - budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and long-acting beta₂-agonist (LABA).⁴ SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of asthma.⁴

Important Safety Information

Long acting beta₂-adrenergic agonists may increase the risk of asthma-related death. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on other asthma-controller medications (e.g., low-to-medium dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with two maintenance therapies. Data from a large placebo-controlled U.S. study compared the safety of another long-acting beta₂-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to formoterol (a long-acting beta₂-adrenergic agonist), one of the active ingredients in SYMBICORT.

SYMBICORT is not indicated for the relief of acute bronchospasm.

SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma.

Particular care is needed for patients who are transferred from systemically active corticosteroids. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Patients who are receiving SYMBICORT twice daily should not use additional formoterol or other long-acting inhaled beta₂-agonists for any reason.

Common adverse events reported in clinical trials, occurring in > 5 percent of patients, regardless of relationship to treatment, include nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, and stomach discomfort.

Please see full Prescribing Information and visit www.MySYMBICORT.com

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines.  In the United States, AstraZeneca is a $13.35 billion dollar healthcare business with 12,200 employees committed to improving people's lives. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

For more information visit www.astrazeneca-us.com.

References:

1. COPD Learn More Breathe Better. National Heart Lung and Blood Institute. Retrieved on 21 Mar 2008. http://www.nhlbi.nih.gov/health/public/lung/copd/index.htm.
2. Rennard, Stephen I., et al. A 12-Month Double-Blind, Double-Dummy, Randomized, Parallel Group, Multicenter Efficacy & Safety Study of SYMBICORT^® pMDI 2 x 160/4.5 µg bid and Placebo in Patients with COPD. [CLINICAL STUDY REPORT].
3. Tashkin, Donald P., et al. A 6-Month Double-Blind, Double-Dummy, Randomized, Parallel Group, Multicenter Efficacy & Safety Study of SYMBICORT^® pMDI 2 x 160/4.5 µg & 80/4.5µg bid Compared to Formoterol TBH, Budesonide pMDI (& the combination) & Placebo in COPD Patients. [CLINICAL STUDY REPORT].
4. Symbicort Prescribing Information.
5. How is COPD Treated? National Heart Lung and Blood Institute. Retrieved on 21 Mar 2008. http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_Treatment.
6. Pocket Guide to COPD Diagnosis, Management, and Prevention. Global Initiative for Chronic Obstructive Lung Disease. Retrieved on 1 Apr 2008.  http://goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=1116.
7. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2007. Retrieved on 21 Apr 2008. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=996.
8. Asthma and Allergy Foundation of American. Asthma Medications. Available at http://www.aafa.org/display.cfm?id=8&sub=16&cont=42. Accessed on 4/25/08.