An editorial published in the NEJM alongside detailed results from the IMPACT study of GlaxoSmithKline and Innoviva's once-daily single inhaler triple therapy Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol) has raised questions over the trial design. In response, GlaxoSmithKline said it did not believe the editorial presented an accurate picture of the product's benefit-risk profile.

Trelegy Ellipta was approved last year in both the US and Europe as a maintenance treatment for certain patients with chronic obstructive pulmonary disease (COPD). GlaxoSmithKline and Innoviva are also looking to expand approval of the therapy based on data from the IMPACT trial, in which Trelegy Ellipta demonstrated superiority to dual combination therapy with Relvar/Breo Ellipta (fluticasone furoate/vilanterol) and Anoro Ellipta (umeclidinium/vilanterol).

Results from the study showed that Trelegy Ellipta led to a 15-percent reduction in the annual rate of on-treatment moderate/severe exacerbations versus Relvar/Breo Ellipta and a 25-percent reduction compared to Anoro Ellipta. In the trial, Trelegy Ellipta was also associated with significant improvements across all key secondary endpoints, with the change from baseline trough forced expiratory volume in one second for the triple therapy being 97 ml versus Relvar/Breo Ellipta and 54 ml compared to Anoro Ellipta.

However, writing in the NEJM, Samy Suissa and Jeffrey Drazen said the design of the IMPACT trial may have artificially inflated the effectiveness of the triple-therapy inhaler over dual bronchodilator treatment. "As such, we think that the IMPACT trial falls short of providing the awaited robust evidence to better understand the potential for stepping up to single-inhaler triple therapy in clinical practice," they wrote.

Suissa and Drazen noted that while the IMPACT trial addressed the relevant clinical question of treatment step-up from a dual long-acting bronchodilator regimen to triple therapy, the patients in the study "were not the natural population in which to study this question, potentially artificially inflating the observed effectiveness of the triple-therapy inhaler over dual bronchodilator treatment."

In response to the editorial, a GlaxoSmithKline spokesperson told FirstWord "we disagree with the...critique of study design and patient population," adding that the trial "was designed in consultation with the FDA, to mirror elements of typical clinical practice." The drugmaker said "the results clearly demonstrate the range of clinically relevant patient benefits" of Trelegy Ellipta compared to Anoro and Breo, which include a reduction in moderate/severe exacerbations, improved lung function and quality of life, as well reducing hospitalisations and on-treatment all-cause mortality versus Anoro.

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