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 chronic obstructive pulmonary disease (COPD). The study evaluated the dose response, efficacy and safety of five doses of '444 administered once-daily for four weeks. All doses achieved statistically significant increases in lung function (trough FEV1) compared to placebo (p<0.05). The changes were dose-dependent with the two highest doses (25 and 50 mcg) exceeding a predefined threshold of 130 mL increase in FEV1 at trough.
"These positive results for '444 in COPD follow recent positive findings in asthma and give us further confidence in the Horizon clinical development programme," commented Darrell Baker, SVP GSK Respiratory Medicines Development Centre.
'444 exhibited a rapid, dose-dependent onset of action with sustained bronchodilator effect over 24 hours. Improvements in lung function 24 hours after the first dose were maintained throughout the 28-day treatment period. Favourable efficacy trends were also seen in a number of other endpoints including improvements in peak expiratory flow both in the morning and evening and reduced use of rescue medication.
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 frequently reported adverse event in the study and was most common in the placebo group. There was no effect on average heart rate (a known side-effect of beta-agonists) at any dose compared to placebo. Serious adverse events common in an elderly COPD population were reported with low frequency and not seen in either of the two high dose groups and not associated with beta2 agonist pharmacology.
"We are very encouraged by the outcomes of this study in COPD," said Rick E Winningham, chief executive officer at Theravance. "These positive results bring us closer to achieving the goal of the Horizon collaboration which is to develop novel, once-a-day inhaled medicines to bring relief to patients with asthma and COPD."
Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates.