GlaxoSmithKline Plc (GSK) and Theravance, Inc 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 four weeks, showed dose dependent improvements in lung function. All but the two lowest doses of '444 produced statistically significant improvements (p<0.05) in forced expiratory volume in one 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 four 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."
Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction.