GlaxoSmithKline and Innoviva, Inc have announced the publication in the New England Journal of Medicine (NEJM) of the landmark IMPACT study, one of the biggest ever conducted in patients with chronic obstructive pulmonary disease (COPD) with a history of exacerbations.1
In the study, Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol, ‘FF/UMEC/VI’ 100/62.5/25mcg) achieved superiority to members of two different classes of dual combination therapy, Relvar (FF/VI) and Anoro (UMEC/VI), on the primary endpoint of reduction in the annual rate of on-treatment moderate/severe exacerbations (p<0.001) and a range of other clinically important outcomes, including lung function and health-related quality of life.
Results from additional secondary and other endpoints published yesterday, include: A statistically significant 34% reduction in COPD hospitalisations (severe exacerbations) for FF/UMEC/VI compared to UMEC/VI (0.13 vs. 0.19 per year; p<0.001) and a reduction of 13% compared to FF/VI which was not statistically significant (0.13 vs. 0.15; p=0.064).
A reduction in the risk of on-treatment all-cause mortality was observed for both inhaled corticosteroid containing arms compared to UMEC/VI. A 42.1% reduction in the risk of on-treatment all-cause mortality was observed for FF/UMEC/VI compared to UMEC/VI (1.20% vs. 1.88%; p=0.011).
To fully understand the implications of the all-cause mortality observation, off-treatment data also need to be considered. Work is ongoing to investigate this further and will be presented at future scientific meetings.
Dave Allen, Head, Respiratory Therapy Area R&D, GSK, said, “Reducing exacerbations to keep patients out of hospital is a key goal of COPD management alongside improving lung function and quality of life. The IMPACT study shows how Trelegy Ellipta can help patients with a history of exacerbation achieve these goals. We believe its publication in NEJM is an important addition to the evidence base that informs the management of this progressive and debilitating disease.”
Dr. Fernando Martinez, Chief, Division of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, said, “IMPACT significantly advances our understanding of COPD management by addressing a number of key evidence gaps. By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine. As many patients experience frequent exacerbations or ‘flare ups’, which can often result in hospitalisation, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”
The safety profile of single inhaler triple therapy was consistent with the safety profile of the individual components. The most common adverse events across the treatment groups were viral upper respiratory tract infection, worsening of COPD, upper respiratory tract infection, pneumonia and headache. Consistent with previous studies, the incidence of pneumonia as a serious adverse event was 4%, 4%, and 3% for FF/UMEC/VI, FF/VI and UMEC/VI, respectively.
Dr Ted Witek, Senior Vice President and Chief Scientific Officer at Innoviva notes, “The role of inhaled corticosteroids (“ICS”) in COPD have long been debated, and this landmark trial provides further evidence of their benefit in the population studied and compelling data towards clarifying the role of ICS containing regimens in the COPD treatment paradigm. We congratulate our partners at GSK for this vital contribution to the field of respiratory medicine.”
Results from IMPACT were submitted to the regulatory authorities in the US and EU in November 2017 and February 2018, respectively. Further regulatory submissions in other countries are expected in 2018.
- Lipson DA et al. Once-Daily Single Inhaler Triple Versus Dual Therapy in Patients with COPD. New England Journal of Medicine. 2018.