GlaxoSmithKline and Innoviva, have announced positive headline results from the landmark phase III IMPACT study of Trelegy Ellipta, the first and only FDA approved once-daily single inhaler triple therapy comprising an inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA).

Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol, FF/UMEC/VI) is approved for the long-term, once-daily, maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) who are receiving Breo (fluticasone furoate/vilanterol, FF/ VI) and require additional bronchodilation or who are receiving Breo and Incruse (umeclidinium, UMEC).

The IMPACT study, which involved 10,355 patients, met its primary endpoint demonstrating statistically significant reductions in the annual rate of on-treatment moderate/severe exacerbations for FF/UMEC/VI (100/62.5/25mcg) when compared with two, once-daily dual COPD therapies from GSK’s existing portfolio. The study showed a: 15% reduction for FF/UMEC/VI compared with Relvar/Breo Ellipta (FF/VI,100/25mcg); 0.91 vs 1.07 per year; p<0.001, 25% reduction for FF/UMEC/VI compared with Anoro Ellipta (UMEC/VI, 62.5/25mcg); 0.91 vs 1.21 per year; p<0.001

In addition, statistically significant improvements were observed across all pre-specified key secondary endpoints and associated treatment comparisons:  Change from baseline trough FEV1 at week 52 for FF/UMEC/VI compared with FF/VI was 97mL; p<0.001 and for FF/UMEC/VI compared with UMEC/VI was 54mL; p<0.001,  Change from baseline St George’s Respiratory Questionnaire at week 52 for FF/UMEC/VI compared with FF/VI was -1.8 units; p<0.001 and for FF/UMEC/VI compared with UMEC/VI was -1.8 units; p<0.001, Analysis of time to first on-treatment moderate/severe COPD exacerbation demonstrated a 14.8% reduction in risk for FF/UMEC/VI compared with FF/VI; p<0.001, and a 16.0% reduction in risk for FF/UMEC/VI compared with UMEC/VI; p<0.001

Based on review of the headline data, the safety profile of FF/UMEC/VI was consistent with the known profile of the individual medicines and their dual combinations.  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. The incidences of the most frequent serious adverse events were worsening of COPD: 11%, 11% and 13% for FF/UMEC/VI, FF/VI and UMEC/VI, respectively; and pneumonia: 4%, 4% and 3% for FF/UMEC/VI, FF/VI and UMEC/VI, respectively.

Patrick Vallance, President R&D, GSK, said: “We are delighted with the positive results achieved in the IMPACT study. This is the first study to report a comparison of a single inhaler triple therapy with two dual therapies, providing much needed clinical evidence about the ability of a single inhaler triple therapy to reduce exacerbations.  It is important to note that all treatments were comprised of different combinations of the same component molecules administered in the same Ellipta inhaler, in a single dose, once a day to allow direct treatment comparisons. We hope these results will inform global guidelines and look forward to sharing the results with regulatory authorities. We will continue to analyse the wealth of data generated to further the understanding of the treatment of COPD.”

Mike Aguiar, CEO of Innoviva, Inc. commented: “The results of the IMPACT study have been long awaited by the medical community. We believe these data will significantly contribute to the body of evidence on the use of single inhaler triple therapy, as well as the ongoing role of ICS/LABA and LAMA/LABA treatments in appropriate patients with COPD.”

Full results will be presented at upcoming scientific meetings and in peer-reviewed publications.

On 14 September 2017, GSK and Innoviva, Inc. announced that the EU Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending marketing authorisation for Trelegy Ellipta as a maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist.

On 18 September 2017, GSK and Innoviva, Inc. announced that the US Food and Drug Administration (FDA) approved Trelegy Ellipta for the long-term, once-daily, maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, who are on a fixed-dose combination of fluticasone furoate and vilanterol for airflow obstruction and reducing exacerbations in whom additional treatment of airflow obstruction is desired or for patients who are already receiving umeclidinium and a fixed-dose combination of fluticasone furoate and vilanterol. Trelegy Ellipta is not indicated for relief of acute bronchospasm or the treatment of asthma.  

Global regulatory filings with the IMPACT study are expected to commence in the second quarter of 2018 for consideration of expansion of the indicated patient population.