GSK and Theravance announce positive results from four pivotal phase III studies for once-daily LAMA/LABA (UMEC/VI) in COPD

GlaxoSmithKline plc (LSE: GSK) and Theravance, Inc. (NASDAQ: THRX) today announced the results of four pivotal phase III studies of investigational LAMA/LABA involving over 4,000 patients with chronic obstructive pulmonary disease (COPD). These four studies include 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.

Darrell Baker, SVP Respiratory Portfolio Optimisation Leader at GSK said: “We are very encouraged by the results of these initial studies for our LAMA/LABA, an important cornerstone of our broad respiratory development portfolio. 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. Subject to successful completion of the ongoing studies, we plan to commence global regulatory filings from the end of this year.”

Rick E Winningham, Chief Executive Officer of Theravance said: “There remains a great unmet medical need in COPD. In particular, physicians have stated that there is still a need to help patients breathe better. We believe the results of these initial studies demonstrate a potential benefit for patients with COPD.”

Placebo-Controlled Efficacy Studies

The first 24-week, randomised, double-blind, placebo-controlled study evaluated the efficacy and safety of UMEC/VI 125/25mcg, VI 25mcg, UMEC 125mcg and placebo. This study randomised 1,493 patients. 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, randomised, double-blind, placebo-controlled study evaluated the efficacy and safety of UMEC/VI 62.5/25mcg, VI 25mcg, UMEC 62.5mcg and placebo. This study randomised 1,536 patients. 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).

Active Comparator Efficacy Studies

The first 24-week, randomised, double-blind, double-dummy, parallel-group study compared the efficacy and safety of UMEC/VI 62.5/25mcg and 125/25mcg with VI 25mcg and tiotropium 18mcg. This study randomised 846 patients. 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, randomised, double-blind, double-dummy, parallel-group study compared the efficacy and safety of UMEC/VI 62.5/25mcg and 125/25mcg with UMEC 125mcg and tiotropium 18mcg. This study randomised 872 patients. 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). The incidence of serious adverse events across all treatment groups was similar (3-6% of placebo group, 5-7% of VI group, 6% of UMEC 62.5mcg group, 5-7% UMEC 125mcg group, 5-10% UMEC/VI 62.5/25mcg group, 2-7% of UMEC/VI 125/25mcg group and 4-6% tiotropium).

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 programme 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.

The full results of all these studies, together with additional data from phase IIb dose-ranging studies of UMEC, will be presented at future scientific meetings.

Other Respiratory Development Programmes

The data from these studies will also contribute to the future regulatory submissions for GSK’s UMEC monotherapy, with global filings commencing in 2013.

UMEC/VI is one of several late-stage assets in the GSK respiratory development portfolio, which includes RELOVAIR™ fluticasone furoate/vilanterol (FF/VI), VI monotherapy and MABA (GSK961081), developed in collaboration with Theravance, as well as GSK’s investigational medicines FF monotherapy, UMEC monotherapy and anti-IL5 MAb (mepolizumab).