Pivotal Data Showed SYMBICORT(R) Improved Lung Function in Adults with COPD

WILMINGTON, Del. (Map) - WILMINGTON, Del., Oct. 29 /PRNewswire-FirstCall/ -- Data presented today from two pivotal efficacy and safety trials, SHINE and SUN, demonstrated that SYMBICORT(R) (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol significantly improved lung function and was well-tolerated in patients with moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) relative to budesonide and formotorol administered alone, and placebo.(1,2,3,4) Both trials showed safety profiles consistent with the established profiles in asthma for each product.(2,4) In addition, an analysis of these trials showed that patients receiving SYMBICORT achieved a bronchodilatory effect, or opening of the airways, similar to formoterol DPI, and a more rapid effect than that achieved by either budesonide pMDI or placebo.(5) Results were presented today at CHEST 2008, the 74th annual international scientific assembly of the American College of Chest Physicians, held in Philadelphia, October 25-30, 2008.

In April 2008, AstraZeneca submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for SYMBICORT for the long-term maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema. SYMBICORT is a combination therapy currently indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older.(6) SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of asthma.(6)

"Results of the SHINE and SUN trials demonstrated that SYMBICORT improved lung function and was well-tolerated by study patients with COPD,(1,2,3,4) and if approved by the FDA, it could offer a new treatment option for the millions of Americans suffering from this debilitating disease," said lead investigator Donald Tashkin, M.D., of the University of California, Los Angeles (UCLA). "Data from these trials also showed that a greater percentage of patients achieved a 15 percent improvement in FEV1 within 15 minutes with SYMBICORT as compared to budesonide and placebo on the day of randomization and end of treatment."(5)

SHINE Study Results (Abstracts 298 and SHINE Safety)

The efficacy and tolerability of SYMBICORT was assessed in a six-month, randomized, double-blind, multicenter trial evaluating 1,704 patients ages 40 years and older with moderate to very severe COPD.(1,2) After two weeks of treatment based on previous therapy (inhaled corticosteroids (ICS) and short-acting bronchodilators were allowed), patients were then randomized to receive twice-daily treatment with two inhalations of SYMBICORT pMDI 160/4.5 micrograms (mcg), SYMBICORT pMDI 80/4.5 mcg, budesonide pMDI 160 mcg + formoterol DPI 4.5 mcg, budesonide pMDI 160 mcg, formoterol DPI 4.5 mcg or placebo.(1,2) Study results include:

-- Both SYMBICORT doses (160/4.5 and 80/4.5 mcg) demonstrated a significantly greater improvement from baseline in pre-dose forced expiratory volume in one second (FEV1) (P Less Than or Equal To .001) and one-hour post-dose FEV1 compared with budesonide (P<.001).(1)

-- SYMBICORT 160/4.5 mcg also demonstrated a significant (P=.026) improvement from baseline for pre-dose FEV1 compared with formoterol.(1)

-- Improvements from baseline in morning and evening peak expiratory flow (PEF) were significantly (P Less Than or Equal To .016) greater for both SYMBICORT doses compared with formoterol, budesonide and placebo.(1)

-- Both SYMBICORT doses significantly (P<.028) improved the sum of Breathlessness, Cough and Sputum Scores (BCSS), sleep score, awakening-free nights, and rescue medication use versus placebo.(1)

-- Both doses of SYMBICORT were well-tolerated for six months relative to its monocomponents and placebo.(2) The incidence of pneumonia-related adverse events were similar for all treatment arms compared to placebo.(2)

-- The incidence of other potential lung infections (e.g., bronchitis) was generally higher for all active treatment groups, except SYMBICORT 80/4.5 mcg, compared to placebo.(2)

-- The most common drug-related adverse events were oral candidiasis, dysphonia, a voice disorder,(7) and headache.(2)

SUN Study Results (Abstracts 303 and 308)

The long-term efficacy and tolerability of SYMBICORT was assessed in a 12-month, randomized, double-blind, multicenter study evaluating 1,964 patients ages 40 years and older with moderate to very severe COPD.(3,4) After two weeks of treatment based on previous therapy (ICS and short-acting bronchodilators were allowed), patients were then randomized to receive twice-daily treatment with two inhalations of SYMBICORT pMDI 160/4.5 mcg, SYMBICORT pMDI 80/4.5 mcg, formoterol DPI 4.5 mcg or placebo.(3,4) Study results include:

-- SYMBICORT 160/4.5 mcg demonstrated significantly (P Less Than or Equal To .023) greater improvements from baseline in pre-dose FEV1 and one-hour post-dose FEV1 compared with formoterol.(3)

-- Improvements from baseline in morning and evening PEF were significantly (P Less Than or Equal To .017) greater for both SYMBICORT doses compared with formoterol and placebo.(3)

-- Exacerbation rates were significantly (P Less Than or Equal To .004) reduced by approximately 25-30 percent with both doses of SYMBICORT compared to formoterol and by approximately 40 percent compared to placebo.(3)

-- Both SYMBICORT doses demonstrated significantly (P<.038) greater improvements in BCSS (160/4.5 mcg only), sleep score, awakening-free nights (80/4.5 mcg only), and rescue medication use versus formoterol.(3)

-- Both doses of SYMBICORT were well-tolerated versus formoterol and placebo for up to 12 months.(4) The incidence of pneumonia-related adverse events were similar for all treatment arms compared to placebo.(4)

-- The incidence of other potential lung infections (e.g., bronchitis) was slightly higher in the active treatment groups compared to placebo.(4)

-- The most common drug-related adverse events were oral candidiasis, dysphonia and muscle spasms.(4)

Onset of Bronchodilation Results (Abstract 302)

An analysis of the data from the SHINE (Study I) and SUN (Study II) trials assessed the onset of bronchodilation, defined as the time to achieve 15 percent or greater improvement in FEV1, within the 1,109 study participants ages 40 years and older with moderate to very severe COPD for six and 12 months, respectively.(5) Study results include:

-- Onset of bronchodilation was significantly (P<.001; Wilcoxon rank sum test) earlier for patients receiving both doses of SYMBICORT (160/4.5 and 80/4.5 mcg) and formoterol compared with placebo in both studies.(5) Onset also was significantly earlier for both doses of SYMBICORT versus budesonide (assessed in Study I only).(5)

-- Median time (minutes) to 15 percent FEV1 improvement was as follows: SYMBICORT 160/4.5 mcg (6.8 [I]; 4.2 [II]), SYMBICORT 80/4.5 mcg (4.9 [I]; 4.8 [II]) and formoterol (9.0 [I]; 6.0 [II]).(5)

-- The percentages of patients achieving Greater Than or Equal To 15 percent FEV1 improvement within 15 minutes post-dose were as follows: SYMBICORT 160/4.5 mcg (58.6% [I]; 72.7% [II]), SYMBICORT 80/4.5 mcg (60.8% [I]; 70.2% [II]), budesonide (19.8% [I]), formoterol (61.5% [I]; 60.5% [II]), and placebo (13.0% [I]; 13.6% [II]).(5)

-- Compared with the day of randomization, the median time to onset of bronchodilation for SYMBICORT was maintained at treatment end in both studies, but increased in the formoterol group.(5)

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.(8) Some estimates also suggest that 12 million more people have COPD but remain undiagnosed.(8) COPD is a disorder encompassing two serious lung diseases -- emphysema and chronic bronchitis -- which result in decreased quality of life, chronic airway inflammation and progressive loss of lung function, making it difficult to breathe normally.(8) Common symptoms include shortness of breath, chronic cough, wheezing and excess mucus.(8) In patients with severe to very severe COPD, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends the addition of inhaled corticosteroids (ICS) to long-acting beta2-agonists (LABA), in addition to other treatment options, to reduce exacerbations and improve lung function and health status.(9) COPD is a progressive disease, which means people with COPD can expect lung function to worsen over time.(9) When symptoms are severe, it can be difficult for a person to perform simple, daily tasks.(8) As the disease progresses, people with COPD may eventually require supplemental oxygen and may ultimately have to rely on mechanical ventilatory assistance.(10)

About SYMBICORT

SYMBICORT is a combination therapy indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older.(6) SYMBICORT is not indicated in patients whose asthma can be successfully managed by inhaled corticosteroids along with occasional use of inhaled short-acting beta2- agonists.(6) Administered twice daily,(6) SYMBICORT is a combination of two proven asthma medications-budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and long-acting beta2-agonist (LABA).(6) SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of asthma.(6)

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, including 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) Tashkin, D.P., Rennard, S.I., Martin, P., Goldman, M., Silkoff, P.E. Efficacy of Budesonide/Formoterol Administered Via One Pressurized Metered- Dose Inhaler Over 6 Months in Patients with Chronic Obstructive Pulmonary Disease [poster]. CHEST, Oct. 25-30, 2008, Philadelphia. Poster #298.

(2) Tashkin, D.P., Rennard, S.I., Martin, P., Goldman, M., Silkoff, P.E. Tolerability of Budesonide and Formoterol Administered in One Pressurized Metered-Dose Inhaler Over 6 Months in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease [poster]. CHEST, Oct. 25-30, 2008, Philadelphia. SHINE Safety Poster.

(3) Rennard, S.I., Tashkin, D.P., McElhattan, J., Goldman, M., Silkoff, P.E. Long-term Efficacy of Budesonide/Formoterol Administered Via One Pressurized Metered-Dose Inhaler in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease [poster]. CHEST, Oct. 25-30, 2008, Philadelphia. Poster #303.

(4) Rennard, S.I., Tashkin, D.P., McElhattan, J., Goldman, M., Silkoff, P.E. Long-term Tolerability of Budesonide and Formoterol Administered Via One Pressurized Metered-Dose Inhaler in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease [poster]. CHEST, Oct. 25-30, 2008, Philadelphia. Poster #308.

(5) Nelson, H.S., Tashkin, D.P., Rennard, S.I., Martin, P., Goldman, M., Silkoff, P.E. Onset of Bronchodilation with Budesonide and Formoterol Administered in One Pressurized Metered-Dose Inhaler in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease [poster]. CHEST, Oct. 25- 30, 2008, Philadelphia. Poster #302.

(6) SYMBICORT Prescribing Information.

(7) Spasmodic Dysphonia. National Institute on Deafness and Other Communication Disorders. Retrieved 2 October 2008. http://www.nidcd.nih.gov/health/voice/spasdysp.asp.

(8) COPD Learn More Breathe Better. National Heart Lung and Blood Institute. Retrieved on 1 October 2008. http://www.nhlbi.nih.gov/health/public/lung/copd/what-is-copd/index.htm.

(9) Pocket Guide to COPD Diagnosis, Management, and Prevention. Global Initiative for Chronic Obstructive Lung Disease. Retrieved on 1 October 2008. http://goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=1116.

(10) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2007. Retrieved on 1 October 2008. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=996.