Trelegy Ellipta IMPACT Results Bolster Results Versus Dual Therapies

David A. Lipson, MD

More data on the benefits and risks of single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; Trelegy Ellipta) from the phase 3 IMPACT trial show positive indications for the first-ever inhaler therapy of its kind.

A month after receiving an expanded indication from the US Food and Drug Administration (FDA) to provide maintenance of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), GlaxoSmithKline (GSK) has presented new data from the pivotal phase 3 IMPACT trial.

The data was presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, on May 20. The trial compared Trelegy Ellipta — a combination inhaled corticoid steroid (ICS), long-acting muscarinic agonist (LAMA), and long-acting beta agonist (LABA) — to dual therapies ICS/LABA and LAMA/LABA in patients with COPD.

Trelegy Ellipta was first approved by the FDA in September 2017. Its original indication specified it was for the treatment of patients with COPD, including chronic bronchitis and/or emphysema, who were on a fixed-dose combination of FF/VI for airflow obstruction and reducing exacerbations, who need additional treatment of airflow obstructions, or for patients who already receiving UMEC and a fixed-dose combination of FF/VI.

David A. Lipson, MD, corresponding study author and GSK researcher, told MD Magazine that the trial intent was to understand the benefits and risks of the triple combination therapy in treating COPD, as well as improving an understanding of what particular patients need ICS therapy or maximal bronchodilation.

Researchers randomized 10,355 patients being treated for COPD to either FF/UMEC/VI (4151), FF/VI (4134) or UMEC/VI (2070). Lipson lightheartedly noted to a crowded audience at the ATS meeting that the benefit of a large-population study is that patient demographics end up consistent. Across the 3 treatment arms, patients were consistently around 65 years old, with a two-thirds population consisting of males and former smokers.

Unique from standard trials, researchers did not require patients to gradually move off their then-COPD medication before beginning the 52-week trial, because “that’s not what happens in real life” to patients, Lipson said. Despite there being a mortality analysis included in the trial, researchers also asked patients who discontinued investigative care to remain included in the study analysis.

The trial’s primary endpoint was a significant reduction annual rate of moderate to severe exacerbations with FF/UMEC/VI versus that of FF/VI and UMEC/VI. Researchers also gauged for reduction in risk of first on-treatment of moderate to severe exacerbation with the triple-drug single therapy.

Following 52 weeks of therapy, patients receiving FF/UMEC/VI reported an estimated annual exacerbation rate of 0.91 — a rate 15% improved than that of patients receiving FF/VI (1.07; 95% CI 10-20; P < 0.001), and 25% improved from patients receiving UMEC/VI (1.21; 95% CI 19-30; P < 0.001).

Patients receiving the triple therapy also reported reductions in risk for first on-treatment moderate to severe exacerbation versus the dual therapies — 14.6% that of patients on FF/VI (95% CI; 9.3-19.9) and 16.0% that of patients on UMEC/VI (95% CI; 9.4-22.1) (P < 0.001).

In gauging for safety, FF/UMEC/VI patients reported similar risks for cardiovascular effects (10%) to that of dual therapies — but a statistically significant increased risk for pneumonia (8%). However, Lipson noted this rate was consistent with previous study results.

Patients also reported improved metrics in lung function and quality of life which, when coupled with the exacerbation frequency reduction and the consistent safety profile, indicated a positive benefit/risk ratio for FF/UMEC/VI in treating COPD.

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