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GSK and Theravance announce positive phase 2b results for LABA, `444 in the Horizon Asthma Development programme


Initial results demonstrate potential of `444 in the treatment of patients with moderate to severe asthma

London UK and South San Francisco, CA

GlaxoSmithKline Plc (GSK) and Theravance, Inc. (NASDAQ: THRX) today announced positive results from the phase 2b study of the novel, long-acting beta agonist (LABA) GW642444 (‘444) in patients with moderate to severe asthma. The study, which was designed to evaluate the efficacy of five doses of ‘444 administered once-daily for 4 weeks, showed dose dependent improvements in lung function. All but the two lowest doses of ‘444 produced statistically significant improvements (p less than 0.05) in forced expiratory volume in 1 second (FEV1) measured 23-24 hours after the last dose in a large study population of asthmatics already being treated with inhaled corticosteroids and short acting beta agonist rescue medication as needed.

Further evidence of once-daily efficacy was observed in a number of secondary endpoints including improvements in peak expiratory flow both in the morning and evening, and the percentage of symptom-free days and rescue-free days. Use of rescue medication was significantly lower in patients receiving the three highest doses of ‘444, compared to patients on placebo. Onset of action was dose-dependent with the bronchodilator effect being sustained over 24 hours. Furthermore, improvements in lung function 24 hours after the first dose were maintained throughout the 28 day treatment period.

Throughout the 4 week study period ‘444 was well tolerated at all doses and the frequency of adverse events was comparable to placebo. Headache was the most commonly observed adverse event in all arms and was comparable to placebo. The highest dose (50 mcg) produced a small change in heart rate (a known effect of beta agonists) that did not exceed the pre-defined clinically relevant threshold. There were no serious adverse events reported in the study. These data show that in asthma, ‘444 demonstrated statistically significant once-daily bronchodilation versus placebo and was well tolerated.

Darrell Baker, SVP GSK Respiratory Medicines Development Centre commented, “The Horizon development programme builds on GSK’s extensive respiratory heritage and confirms our continued commitment to bring novel respiratory medicines to patients. We are encouraged by the 24-hour duration of action and sustained response over 28 days. A once-daily treatment option is an important new development in a disease where half of all patients are not well controlled and compliance remains less than ideal.”

“The goal of the collaboration with GSK is to develop a novel, once-a-day inhaled combination medicine comprised of a LABA and a corticosteroid to bring relief to patients with asthma and chronic obstructive pulmonary disease,” said Rick E Winningham, Chief Executive Officer at Theravance. “Today’s positive results in asthma together with the results of the phase 2b LABA ‘444 COPD study in early 2009 will give us a better understanding of the safety and efficacy of ‘444 across both populations.”

Study design

A total of 607 patients with moderate to severe asthma who were receiving an inhaled corticosteroid were enrolled into this double-blind, placebo controlled study. Patients received one of five doses of ‘444, (3, 6.25, 12.5, 25 and 50mcg) or placebo, administered once daily via a novel inhaler. All patients were permitted to use rescue medication as needed.

The primary endpoint to assess efficacy was change in trough (23-24 hour) FEV1 from baseline after 28 days. The secondary endpoints included serial 24 hour FEV1 on days 1 and 28, AM and PM peak expiratory flow averaged over the 28 day treatment period and percent of symptom-free and rescue-free 24 hour periods.

Further data from the Horizon asthma development programme are anticipated in early 2009, including three studies of the inhaled corticosteroid (ICS) GW685698 (‘698) – an enhanced-affinity, glucocorticoid. In parallel, enabling studies involving ’444 and ’698 given in combination have also been undertaken.

A large phase 2b dose-optimisation study of ‘444 in patients with COPD remains ongoing as part of the Horizon programme. Overall the Horizon programme has enrolled in excess of 3,000 asthma and COPD patients globally.


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