Breo Ellipta/Relvar Ellipta fails to meet primary endpoint in SUMMIT study of COPD patients with risk of CV disease- GSK + Theravance

GlaxoSmithKline plc and Theravance, Inc. announced initial results from the Study to Understand Mortality and MorbidITy in COPD (SUMMIT) for Relvar/Breo Ellipta 100/25mcg (fluticasone furoate ‘FF’/vilanterol ‘VI’ or ‘FF/VI’). The study involved 16,485 patients from 43 countries who had chronic obstructive pulmonary disease (COPD) with moderate airflow limitation (FEV1 50-70% predicted) and either a history or increased risk of cardiovascular disease (CVD).

For the primary endpoint of the study, the risk of dying on FF/VI 100/25mcg was 12.2% lower than on placebo over the study period, which was not statistically significant (p=0.137). For the first of two secondary endpoints, FF/VI 100/25mcg reduced the rate of lung function decline (as measured by forced expiratory volume in one second, ‘FEV1’) by 8mL per year compared with placebo (p=0.019). As the primary endpoint was not met, statistical significance cannot be inferred from this result. For the other secondary endpoint, the risk of experiencing an on-treatment cardiovascular (CV) event (CV death, myocardial infarction, stroke, unstable angina and transient ischemic attack [TIA]) at any time was 7.4% lower in patients taking FF/VI 100/25mcg versus placebo which was not statistically significant (p=0.475).

The study also formally analysed a number of additional COPD endpoints assessing the efficacy of FF/VI relative to placebo, which included FEV1 (post-bronchodilator), rate of moderate/severe exacerbations, time to first moderate/severe exacerbation, time to first severe (hospitalised) exacerbation, rate of severe (hospitalised) exacerbation, health related quality of life (as measured by the St George’s Respiratory Questionnaire-COPD total score at 12 months) and health status as measured using the COPD Assessment Tool (CAT) at 12 months. Against these endpoints FF/VI demonstrated an improvement compared to placebo with a nominal P-value of <0.002 for each. As the primary endpoint was not met, statistical significance cannot be inferred from these results.

Comment: The SUMMIT study was intended to show whether the drug lowered the risk of death versus placebo in chronic obstructive pulmonary disease patients who also have a history of or are at higher risk from cardiovascular disease. The results indicated that, while the risk of all-cause mortality was 12.2% lower in the treatment arm, this difference was not statistically significant.