Trelegy Ellipta – IMPACT Study Shows Significant Benefits in COPD Patients

GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today 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 exacerbation.^[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/Breo (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 today, include:

• A statistically significant 34% reduction in COPD hospitalisations (severe exacerbations) for Trelegy compared to Anoro (0.13 vs. 0.19 per year; p<0.001) and a reduction of 13% compared to Relvar/Breo which was not statistically significant (0.13 vs. 0.15; p=0.064).
• A significant reduction in the risk of on-treatment all-cause mortality was observed for both inhaled corticosteroid containing arms compared to Anoro.
• A 42.1% reduction in the risk of on-treatment all-cause mortality was observed for Trelegy compared to Anoro (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.

About IMPACT

The landmark InforMing the PAthway of COPD Treatment (IMPACT) study is the first to directly compare three commonly-used COPD combination treatment classes delivered using the same dose and inhaler. It is the second of two phase 3 studies designed to investigate the efficacy and safety of FF/UMEC/VI in a single inhaler compared to other commonly-used COPD combination treatments.^[2]

It evaluated as its primary endpoint the annual rate of on-treatment moderate/severe exacerbations for FF/UMEC/VI (100/62.5/25mcg) compared with FF/VI (100/25mcg) and UMEC/VI (62.5/25mcg), two once-daily dual COPD therapies from GSK’s existing portfolio. Other secondary and multiple pre-defined protocol ‘other’ endpoints included lung function, patient reported outcomes, including health- related quality of life measures, and all-cause mortality. A range of safety endpoints were also analysed.

Patients had moderate to very severe symptomatic COPD with a history of exacerbation in the prior 12 months. This is representative of approximately 50% of the global COPD patient population.