New post-hoc, pooled analysis shows SYMBICORT® improved airflow obstruction in patients with COPD

Data also finds SYMBICORT achieved improvement in lung function within five minutes

November 9, 2009 – Wilmington, DE – A new post-hoc, pooled analysis of the serial spirometry subset of the pivotal efficacy and safety trials, SHINE and SUN, demonstrated that a large percentage (51.8%) of patients with moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) receiving two inhalations of SYMBICORT® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol 160/4.5 mcg showed improvement of airflow obstruction on day of randomization, as evidenced by the American Thoracic Society (ATS) criteria.1 The ATS criteria assess the impact of bronchodilator therapy on airflow obstruction and are defined as a ≥12 percent improvement and ≥200 mL absolute increase in forced expiratory volume after one second (FEV1) compared to baseline.1 Results were presented at the American College of Asthma, Allergy and Immunology (ACAAI) Annual Meeting in Miami Beach, Florida.

“Airflow obstruction in patients with COPD was considered irreversible; however, professional guidelines and clinical data have shown that airflow obstruction in patients with COPD is more reversible than previously thought,” says lead investigator Bartolome R. Celli, M.D., of Brigham and Women's Hospital in Boston.1,2,3 “These preliminary data found that the combination of budesonide/formoterol (SYMBICORT) reverses airflow obstruction in a large percentage of patients with COPD as defined by ATS standards.”1

Airflow obstruction is a significant component of COPD.4 The ATS criteria are defined as a ≥12 percent improvement and ≥200 mL absolute increase in FEV1 compared to baseline.1 FEV1 is a measure of how much air a person can exhale during the first second after taking a full inhalation and it is a validated way of measuring lung function.5 The added measurement of ≥200 mL in the ATS criteria is harder to achieve for some patients and it helps categorize this reversibility measurement as “significant,” whereas the ≥12 increase in FEV1 is overall considered “meaningful,” according to ATS/European Respiratory Society (ERS) guidance.3  

“These data show that patients with moderate to very severe COPD with an average baseline predose FEV1 of 1.01L, were able to attain an additional 200mL absolute increase in FEV1, which means their lung function improved by approximately 20 percent,” adds Dr. Celli.1 “The degree of reversibility of airflow obstruction observed in patients taking SYMBICORT is significant.”2

The analysis found

• SYMBICORT 160/4.5 mcg demonstrated improvement in airflow obstruction (within 30 minutes postdose) in a large percentage (51.8%) of patients with moderate to very severe COPD based on ATS criteria on the day of randomization1
• At screening, 39.2 percent of the patients who were subsequently randomized to SYMBICORT 160/4.5 mcg had demonstrated reversibility by ATS criteria when tested within 15-30 minutes after receiving two inhalations of albuterol 90 mcg1
• The onset of bronchodilation, based on a ≥15 percent improvement from baseline in FEV1, was rapid (within 5 minutes) with SYMBICORT 160/4.5 mcg on the day of randomization, and this effect was maintained at the end of six months1

SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of COPD.6

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About the Analysis (Abstract P74)
Data were pooled from the serial spirometry subset (n=1,109) and analyzed from common treatment arms within SHINE (6 months, 1,704 patients) and SUN (12 months, 1,964 patients) – which are randomized, double-blind, multicenter efficacy and safety trials that evaluated more than 3,600 patients ages 40 years and older with moderate to very severe COPD.1,6 After two weeks of treatment based on previous therapy (inhaled corticosteroids and short-acting bronchodilators were allowed), patients were randomized to receive two inhalations of one of the following twice daily: SYMBICORT pMDI 160/4.5 mcg (the FDA-approved dosage for COPD), SYMBICORT pMDI 80/4.5 mcg, formoterol DPI 4.5 mcg or placebo, which were the common treatment arms within the trials.1

On the day of screening, FEV1 was measured predose and 15-30 minutes after two inhalations of albuterol 90 mcg.1 Airflow obstruction for albuterol was assessed based on the proportion of patients who achieved ATS criteria 15-30 minutes postdose on the screening day.1 Airflow obstruction for the study medication was assessed based on the proportion of patients who achieved ATS criteria within 30 minutes postdose on the day of randomization.1 Patients refrained from using treatment before testing for >6 hours for albuterol, >8 hours for ipratropium and >48 hours for long-acting bronchodilators.1

Additionally, the study assessed the median time to onset of bronchodilation, or opening of the airways, which was defined as the point at which >50 percent of patients achieved a >15 percent FEV1 improvement, after dosing on the day of randomization and at the end of six months.1

About SYMBICORT
SYMBICORT 160/4.5 mcg is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. For patients with COPD, the approved dosage of SYMBICORT is 160/4.5 mcg two inhalations twice daily. SYMBICORT is also indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older. Administered twice daily, SYMBICORT is a combination of two proven respiratory medications – budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and long-acting beta2-agonist (LABA). SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of COPD or asthma. SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.

For more information about SYMBICORT, please visit www.MySYMBICORT.com/COPD.

Important Safety Information

For patients with COPD, the approved dosage of SYMBICORT is 160/4.5 mcg, two inhalations twice daily

Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids

• In two placebo-controlled SYMBICORT COPD clinical studies, pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group, compared with placebo, while the incidence of lung infections other than pneumonia (e.g., bronchitis) was higher for SYMBICORT than placebo

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

Long-term use of orally inhaled corticosteroids, such as budesonide, a component of SYMBICORT, may affect normal bone metabolism resulting in a loss of bone mineral density

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including budesonide, a component of SYMBICORT

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

Caution should be exercised when considering the coadministration of SYMBICORT with long-term ketoconazole and other known potent CYP3A4 inhibitors

SYMBICORT should be administered with caution in patients being treated with MAO inhibitors or tricyclic antidepressants, or within two weeks of discontinuation of such agents

Particular care is needed for patients being transferred from systemically active corticosteroids to inhaled corticosteroids

Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension

The most common adverse events ≥3 percent reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection

WARNING: 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 with asthma 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 US study that 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 (see WARNINGS in full Prescribing Information).

Please see full Prescribing Information, including boxed WARNING, and visit www.MySYMBICORT.com.

About AstraZeneca
AstraZeneca is engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and in the supply of healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with global healthcare sales of $ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines.  In the United States, AstraZeneca is a $13.5 billion dollar healthcare business.  

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Media Contacts: 

• Dana Settembrino, AstraZeneca: 302-885-6980

References
1. Celli, B., Tashkin, D., Rennard, S., McElhattan, E., Martin, U. Bronchodilator Reversibility and Onset with Budesonide/Formoterol Pressurized Metered-Dose Inhaler (BUD/FM pMDI) in Patients with Chronic Obstructive Pulmonary Disease (COPD) [poster]. ACAAI, November 5-10, Miami, FL. Poster P74.
2. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease Report. Global Initiative for Chronic Obstructive Lung Disease. Retrieved on 21 October 2009.
http://www.goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=2003
3. Pellegrino, R., Viegi, V., Crapo, R.O, et al. Interpretative Strategies for Lung Function Tests. Eur Respir J 2005; 26: 948-968.
4. Standards for the Diagnosis and Management of Patients with COPD. American Thoracic Society/European Respiratory Society. Retrieved on 21 October 2009. http://www.thoracic.org/sections/copd/resources/copddoc.pdf.
5. Essig, Maria G. (2007, January 24). WebMD, Retrieved 21 October 2009. http://www.webmd.com/hw-popup/forced-expiratory-volume-and-forced-vital-capacity.
6. SYMBICORT PI.

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