GlaxoSmithKline and Theravance, a biopharmaceutical company based in San Francisco, issued results from four pivotal phase III studies of investigational LAMA/LABA involving over 4,000 patients with chronic obstructive pulmonary disease (COPD).

The four studies included two 24-week efficacy studies that compared the combination LAMA/LABA, its components and placebo and two 24-week active comparator studies that compared the combination with the LAMA tiotropium, a widely prescribed maintenance bronchodilator for COPD.

LAMA/LABA is a combination of two investigational bronchodilator molecules—GSK573719 or umeclidinium bromide (UMEC), a long-acting muscarinic antagonist (LAMA); and vilanterol (VI), a long-acting beta2 agonist (LABA), administered by a new dry powder inhaler. UMEC/VI is a once-daily investigational medicine currently under development for the maintenance treatment of COPD.

The first of the efficacy studies was a 24-week, randomized, double-blind, placebo-controlled study enrolling 1,493 patients and evaluated the efficacy and safety of UMEC/VI 125/25mcg, VI 25mcg, UMEC 125mcg and placebo. For the pre-specified primary endpoint of trough FEV1 at the end of the treatment period (Day 169), this study showed statistically significant improvements for UMEC and VI individually compared to placebo (p<0.001). The combination UMEC/VI showed statistically significant improvements when compared with the individual components UMEC and VI (p<0.001) and when compared to placebo (238mL, p<0.001).

The second 24-week, randomized, double-blind, placebo-controlled study enrolled 1,536 patients and evaluated the efficacy and safety of UMEC/VI 62.5/25mcg, VI 25mcg, UMEC 62.5mcg and placebo. For the pre-specified primary endpoint of trough FEV1 at the end of the treatment period (Day 169), this study showed statistically significant improvements for UMEC and VI individually compared to placebo (p<0.001). The combination UMEC/VI showed statistically significant improvements when compared with the individual components UMEC and VI (p≤0.004) and when compared to placebo (167mL, p<0.001).

The first of the active comparator studies was a 24-week, randomized, double-blind, double-dummy, parallel-group study enrolling 846 patients and compared the efficacy and safety of UMEC/VI 62.5/25mcg and 125/25mcg with VI 25mcg and tiotropium 18mcg. For the pre-specified primary endpoint of trough FEV1 at the end of the treatment period (Day 169), this study showed statistically significant improvements for both doses of UMEC/VI compared with VI (88-90mL, p<0.001) and tiotropium (88-90mL, p<0.001).

The second 24-week, randomized, double-blind, double-dummy, parallel-group study enrolled 872 patients and compared the efficacy and safety of UMEC/VI 62.5/25mcg and 125/25mcg with UMEC 125mcg and tiotropium 18mcg. The pre-specified primary endpoint was trough FEV1 at the end of the treatment period (Day 169). For the first treatment comparison, UMEC/VI 125/25mcg showed a statistically significant improvement of 74mL compared with tiotropium (p=0.003). For the second comparison, UMEC/VI 125/25mcg showed a numerical but not statistically significant improvement (37mL) compared with UMEC 125mcg (p=0.142). UMEC/VI 62.5/25mcg showed a numerical difference from tiotropium of 60mL (p=0.018) and a numerical difference from UMEC 125mcg of 22mL (p=0.377) in trough FEV1.

In these four studies the most common adverse events across all treatment arms, including placebo, were headache, nasopharyngitis, upper respiratory tract infection, cough, oropharyngeal pain and back pain. Additionally, the incidence of cardiovascular adverse events across all treatment groups was similar (5-9% of placebo group, 7-11% of VI group, 10% of UMEC 62.5mcg group, 7-9% UMEC 125mcg group, 6-11% UMEC/VI 62.5/25mcg group, 6-7% of UMEC/VI 125/25mcg group and 4-8% tiotropium).

"We are very encouraged by the results of these initial studies for our LAMA/LABA, an important cornerstone of our broad respiratory development portfolio,” said Darrell Baker, senior vice president of respiratory portfolio optimization leader, GSK. “These studies, together with our earlier dose-ranging work, give us confidence that this is a once-daily medicine with the potential to benefit many patients with COPD.”

These data form part of the overall evaluation of the efficacy and safety of the UMEC/VI combination and the individual components in approximately 6,000 COPD patients. The ongoing registration program includes a 52-week safety study and two replicate 12-week crossover exercise studies. Subject to successful completion of these additional studies, GSK plans to commence global regulatory submissions for UMEC/VI from the end of 2012, ahead of schedule.