Trelegy Ellipta Improves COPD Exacerbation in Massive, Yearlong Study

A landmark trial comparing triple therapy fluticasone furoate/umeclidinium/vilaterol (FF/UMEC/VI [Trelegy Ellipta]) versus FF/VI (Relvar; Breo) or FF/UMEC (Anoro) found the former is markedly better in reducing annual rate of on-treatment of moderate/severe exacerbations in patients with chronic obstructive pulmonary disease (COPD).

The 10,335-patient Informing the Pathway of COPD Treatment (IMPACT) study compared 52 weeks of once-daily set dose of FF/UMEC/VI (100mg/62.5mg/25mg) to fixed doses of the double-therapy options. Each regimen was administered via a single Ellipta inhaler, and results were measured for a primary outcome of annual rate of moderate or severe COPD exacerbations during treatment.

Enrolled patients were aged 40 years or older, with symptomatic COPD. They also either had a forced expiratory volume in 1 second (FEV1) of less than 50% normally predicted value plus a history of at least one moderate to severe exacerbation in the past year, or an FEV1 of 50-80% of normally predicted value plus at least 2 exacerbations in the past year.

In the 2 weeks leading to treatment randomization, patients continued routine therapy including long-acting beta2 agonists (LABA), long-acting muscarinic antagonist (LAMA), or inhaled glucocorticoid.

The study ran from June 2014 to July 2017 in 37 different countries, with a wide population and lengthy trial period intended to provide “robust results” in the varying populations of patients with COPD, study author David A. Lipson, MD, told MD Magazine.

“There’s probably over 300 million people with COPD worldwide, and a large percentage of them unfortunately experience exacerbations or flare-ups of their disease,” Lipson said. “So, we need to find important answers about the therapies we use to treat this disease.”

Of the 10,355 participants, 4151 received triple therapy, 4134 received FF/VI, and 2070 received FF/UMEC. Just 77% (7991) of the participants finished the trial while receiving investigational therapy.

Patients to receive triple therapy reported a rate of 0.91 moderate to severe exacerbations per year during treatment, while patients to receive FF/VI reported a rate of 1.07 per year, and patients to receive FF/UMEC reported a rate of 1.21 per year (P < 0.001).

The results also showed a significant reduction in the risk of on-treatment all-cause mortality for both inhaled corticosteroid containing arms compared to FF/UMEC. Trelegy’s on-treatment all-cause mortality risk (1.20%) was a 42.1% reduction to that of the combination therapy (1.88%; P = 0.011).

Trelegy Ellipta’s safety profile was consistent with that of the individual components, with the most common adverse events (AEs) across the treatment groups being viral upper respiratory tract infection, worsening of COPD conditions, upper respiratory tract infection, pneumonia, and headaches. Consistent with previous studies, the incidence of pneumonia as a serious AE was between 3-4% for all 3 investigated therapies.

Lipson said there are currently no plans to extend the trial, and that its 52-week duration is long enough to better understand the benefits and risks of combination therapies for COPD.

“Overall, the duration and trial design has provided the field with some very, very important data,” Lipson said.

Trelegy Ellipta, from GlaxoSmithKline, was first approved as a once-daily therapy for patients with COPD in September 2017. As the first triple-combination therapy in a single inhaler to treat COPD, it has already made history. Now Lipson and his research team is seeking out supplemental data from this historically large trial.

“I think it’s going to be terrific,” Lipson said. “We’re really looking forward to future data.”

The study, "Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD," was published online in the New England Journal of Medicine last week.