GSK and Theravance announce positive data from two studies evaluating the efficacy and safety of Incruse™ Ellipta® when added to Relvar®/Breo® Ellipta® in patients with COPD

GlaxoSmithKline plc (LSE/NYSE:GSK) and Theravance, Inc. (NASDAQ: THRX) today announced positive results from two phase III studies, which showed that patients with chronic obstructive pulmonary disease (COPD) who received the anticholinergic, Incruse™ Ellipta® (umeclidinium (UMEC) 62.5mcg), or umeclidinium 125mcg (an unlicensed dose) in addition to Relvar®/Breo® Ellipta® (fluticasone furoate/vilanterol, “FF/VI”), an inhaled corticosteroid / long-acting beta2-agonist combination, achieved an additional improvement in lung function (FEV1) compared to patients receiving FF/VI plus placebo.

The studies showed that for the primary endpoint of trough FEV1 at Day 85, the addition of UMEC 62.5mcg or UMEC 125mcg to FF/VI 100/25mcg resulted in a statistically significant improvement in lung function when compared with FF/VI 100/25mcg plus placebo in patients with COPD.

Darrell Baker, SVP and Head, Global Respiratory Franchise, GSK said: “These data are an important addition to the evidence base supporting the efficacy and safety of Incruse. These studies are also the first to investigate the combined effect of two of the newest medicines from our respiratory portfolio, both of which provide 24 hour efficacy. We will continue to progress our research to expand our understanding of how the combined use of these medicines may provide physicians with another treatment approach to meet the individual needs of their patients.”

“We are pleased with the positive data from these two studies evaluating an open triple therapy, Incruse added to Relvar/Breo Ellipta,” said Rick E Winningham, Chief Executive Officer, Theravance. “With the data reported today, we have further strengthened our understanding of Relvar/Breo Ellipta.”

Study designs:

Both studies (200109 and 200110) were 12-week multicentre, randomised, double-blind placebo-controlled studies. 1238 patients with an established clinical history of COPD and an FEV1 of ≤70%, were randomised and treated in the studies. Eligible patients were randomised 1:1:1 to receive UMEC 62.5mcg, UMEC 125mcg or placebo added to open-label FF/VI 100/25mcg. All treatments were administered once daily in the dry powder inhaler (DPI), Ellipta®.

The primary endpoint for both studies was trough forced expiratory volume in one second (FEV1) on Day 85.

Studies results

200109: For the pre-specified primary endpoint of trough FEV1 (Day 85), compared with placebo added to FF/VI 100/25mcg, both UMEC 62.5mcg and UMEC 125mcg added to FF/VI 100/25mcg, produced statistically significant improvements (UMEC 62.5mcg plus FF/VI 100/25 mcg: 124mL difference versus placebo plus FF/VI 100/25mcg; UMEC 125mcg plus FF/VI 100/25 mcg: 128mL difference versus placebo plus FF/VI 100/25mcg, both p<0.001).

Incidence of on-treatment adverse events (AEs) were 36% UMEC 62.5mcg + FF/VI 100/25mcg, 39% UMEC 125mcg + FF/VI 100/25mcg, 35% placebo + FF/VI 100/25 mcg. The most frequently reported adverse events (greater than or equal to 3% in any treatment group) were headache, nasopharyngitis, back pain, dysgeusia (an abnormal taste or change in taste), cough, diarrhoea and influenza. The incidence of any cardiovascular adverse events of special interest was 2% UMEC 62.5mcg + FF/VI 100/25mcg, 1% UMEC 125mcg + FF/VI 100/25mcg, 3% placebo + FF/VI 100/25mcg. The incidence of pneumonia in the UMEC 125mcg + FF/VI 100/25mcg and the placebo + FF/VI 100/25mcg groups was 1%. There were no reported cases of pneumonia in the UMEC 62.5mcg + FF/VI 100/25mcg group. One death was reported in the placebo + FF/VI 100/25mcg group and was deemed non drug related by the investigator. There were no deaths reported in the UMEC + FF/VI 100/25mcg treatment groups.

200110: For the pre-specified primary endpoint of Trough FEV1 (Day 85), compared with placebo added to FF/VI 100/25mcg, UMEC 62.5mcg and UMEC 125mcg added to FF/VI 100/25mcg, produced statistically significant improvements (UMEC 62.5mcg plus FF/VI 100/25 mcg: 122mL difference versus placebo plus FF/VI 100/25mcg; UMEC 125 mcg plus FF/VI 100/25 mcg: 111mL difference versus placebo plus FF/VI 100/25mcg, both p<0.001).

Incidence of on-treatment adverse events (AEs) were 33% UMEC 62.5mcg + FF/VI 100/25mcg, 30% UMEC 125mcg + FF/VI 100/25mcg, 39% placebo + FF/VI 100/25mcg. The most frequently reported adverse events (greater than or equal to 3% in any treatment group) were nasopharyngitis, headache and back pain. The incidence of any cardiovascular adverse events of special interest was similar across treatment groups (<1% UMEC 62.5mcg + FF/VI 100/25mcg, 1% UMEC 125mcg + FF/VI 100/25mcg, 3% placebo + FF/VI 100/25mcg). The incidence of pneumonia was the same (<1%) in all treatment groups. Four deaths were reported in the placebo + FF/VI 100/25mcg group and one death was reported in the UMEC 62.5mcg + FF/VI 100/25mcg treatment group. All deaths were deemed non drug related by the investigator.

Umeclidinium 62.5mcg inhalation powder, under the brand name Incruse Ellipta, is only approved for use in the US, Canada and Europe for COPD. It is not approved anywhere else in the world. Umeclidinium 125mcg is not an approved dose anywhere in the world.

The full results of these studies will be posted onto clinicaltrials.gov and presented at a future scientific meeting.