Symbicort Improved Small Airway Function in Asthma Patients

Studies are First to Examine Effect of SYMBICORT pMDI on Small Airways

Newswise — Results from three newly presented studies evaluating the maintenance combination asthma therapy, SYMBICORT® (budesonide/formoterol fumarate dihydrate), showed significant improvement in small airway function in patients ages 12 years and older with asthma previously receiving inhaled corticosteroid (ICS) therapy.^1,2 Small airways play an important role in the disease, and treatments that go beyond the central airways to reach the small airways may offer benefits in controlling persistent asthma.^1,2 Two 12-week studies (Poster 602) and one 52-week study (Poster 291) demonstrated that SYMBICORT provided greater improvements in small airway function compared to its mono-components, budesonide (Posters 602, 291) and formoterol (Poster 602), and placebo (Poster 602).^1,2 Results were presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting held in Washington, D.C., March 13-17, 2009.

"These studies are the first to evaluate and suggest an effect of SYMBICORT pMDI on mid-expiratory flow rates, one potential measure of small airway function, and therefore more studies are needed to further examine the drug's impact," ² said lead investigator Dr. David Pearlman, Colorado Allergy and Asthma Centers.

"Small airways can be subject to inflammation and smooth muscle constriction, which are two main causes of asthma symptoms.^2,3 Treatments that are able to reduce bronchial constriction and reduce inflammation in this area may be beneficial to patients with asthma." ²

Small airways, also known as bronchioles, are thin tubes less than two millimeters (mm) in diameter that branch off the central airways, which include the windpipe (trachea) and bronchial tubes entering the lung.^2,4 Small airways are the final and smallest divisions of the lungs and end in bunches of tiny round air sacs called alveoli.⁴ The exchange of oxygen between the lung and the bloodstream takes place at the alveoli.⁴ Because of their small size and the fact that they contain smooth muscle, small airways are very susceptible to further narrowing from inflammation and muscle constriction resulting from asthma.⁵ Therefore, treatments that are able to reduce inflammation and muscle constriction in small airways may improve lung function in asthma patients.²

About Poster 602 The efficacy of SYMBICORT was assessed in two 12-week, randomized, double-blind, double-dummy studies of 1,076 patients ages 12 years and older with asthma previously receiving ICS maintenance therapy.² In Study I, after two weeks of treatment with budesonide pressurized metered-dose inhaler (pMDI) 80 micrograms (mcg) two inhalations twice-daily, symptomatic patients with moderate to severe asthma were randomized to receive twice-daily treatment with two inhalations of SYMBICORT pMDI 160/4.5 mcg, budesonide pMDI 160 mcg + formoterol dry powder inhaler (DPI) 4.5 mcg, budesonide pMDI 160 mcg, formoterol DPI 4.5 mcg or placebo.² In Study II, after two weeks of treatment with placebo, symptomatic patients with mild to moderate asthma were randomized to formoterol DPI 4.5 mcg or placebo, as well as SYMBICORT pMDI (80/4.5 mcg) and budesonide pMDI (80 mcg), all taken as two inhalations twice-daily.²

Results from Study I showed that SYMBICORT produced significantly greater improvements (P<.05) in pre-dose lung function (FEF25-75% " forced expiratory flow during the middle half of exhalation, a measure of small airways obstruction) compared to formoterol and placebo.² FEF25-75% declined over 12 weeks for patients receiving formoterol and placebo.² Patients receiving SYMBICORT and budesonide had similar improvements in FEF25-75% that were maintained over 12 weeks.² Results from Study II demonstrated that SYMBICORT significantly improved (P<.05) pre-dose FEF25-75% versus budesonide, formoterol and placebo.² Improvements were maintained in the SYMBICORT group throughout the 12-week treatment period in both studies.²

About Poster 291 SYMBICORT was assessed in a 52-week randomized, double-blind, parallel-group, single-dummy safety study of 708 patients ages 12 years and older with moderate to severe asthma previously receiving ICS therapy, either alone or in combination with other controller medications.¹ After two weeks of treatment with budesonide pMDI 160 mcg two inhalations twice-daily, patients were randomized to receive twice-daily treatment with two inhalations of SYMBICORT pMDI 160/4.5 mcg (the highest approved dose), four inhalations twice-daily of SYMBICORT pMDI 160/4.5 mcg (twice the maximum approved dose), or budesonide pMDI 160 mcg four inhalations twice-daily (twice the ICS dose of the highest approved dose of SYMBICORT).^1,6

Results demonstrated that patients receiving both doses of SYMBICORT experienced significantly greater improvements in both pre-dose (P<.05) and post-dose (P<.001) FEF25-75% versus budesonide.1G,H These improvements were maintained for up to one year without dimunition.^1I

About SYMBICORTSYMBICORT 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.⁶ For patients with COPD, the approved dosage of SYMBICORT is 160/4.5 mcg two inhalations twice daily.⁶ SYMBICORT is also indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older.⁶ 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).⁶ SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of COPD or asthma.⁶

Important Safety InformationLower 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.

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

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

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. Some patients may experience an increase in blood pressure or heart rate.

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

Common adverse events reported in asthma clinical trials, occurring in > 5% of patients, included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, and stomach discomfort.

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

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.

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References

1. Zangrilli, J.G., McElhattan, J., O'Brien, C.D., Baker, J.W. Predose and Postdose Forced Expiratory Flow Between 25% and 75% (FEF25%-75%) in Adolescents and Adults With Asthma Treated With Twice-Daily Budesonide/Formoterol Pressurized Metered-Dose Inhaler (BUD/FM pMDI) or BUD pMDI for 1 Year [poster]. AAAAI, March 13-17, 2009, Washington, D.C. Poster #291.2. Pearlman, D.S., Uryniak, T., O'Brien, C.D., Martin, U.J. Predose Forced Expiratory Flow Between 25% and 75% (FEF25%-75%) in Inhaled Corticosteroid (ICS)"Dependent Patients With Mild to Moderate or Moderate to Severe Persistent Asthma Receiving Budesonide/Formoterol Pressurized Metered-Dose Inhaler (BUD/FM pMDI) [poster]. AAAAI, March 13-17, 2009, Washington, D.C. Poster #602.3. Diseases and Conditions Index: Asthma. National Heart Lung and Blood Institute. Retrieved on 24 February 2009. http://www.nhlbi.nih.gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html. 4. Diseases and Conditions Index: How the Lungs Work. National Heart Lung and Blood Institute. Retrieved on 24 February 2009. http://www.nhlbi.nih.gov/health/dci/Diseases/hlw/hlw_respsys.html. 5. Persson, C.G.A. Small airway relaxation—A forgotten medical need. Pulmonary Pharmacology & Therapeutics; 2008: 21:1. 6. SYMBICORT Prescribing Information.