GSK and Theravance announce results from the SUMMIT COPD CV Survival Study

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. 

Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing. Cigarette smoke, breathing in second-hand smoke, air pollution including biomass fuels, chemical fumes and dust from the environment or workplace can all contribute to COPD.

COPD mortality is increasing and is the third leading cause of death globally. COPD often coexists with other chronic diseases and epidemiological data suggests that CVD or CV risk occurs in nearly half of all patients with COPD. CVD is the number one killer of mild to moderate COPD patients and patients with both COPD and CVD or CV risk were observed to have a mortality rate double that of COPD patients without CVD in studies of up to 15 years in duration.

Breo Ellipta inhaler Trial Fails to Show Extension of Life

UK based Pharmaceutical firm GlaxoSmithKline PLC has failed to show that the company’s Breo Ellipta inhaler extends life in patients with chronic obstructive pulmonary disease, dashing hopes of a sales boost for the product. Glaxo had hoped that the so-called Summit study, which tested Breo against a placebo in 16,485 patients from 43 countries, would demonstrate that the product prolonged life as well as helped with breathing.

Summit was the first study to test the effect on survival of inhaler products like Breo, which open up the airways to ease breathing in patients with asthma or COPD. It enrolled patients at higher risk of cardiovascular disease to see if Breo could bring added survival benefits to this group. About half of the people diagnosed with COPD are at heightened risk of cardiovascular disease.

The company said patients on Breo were 12.2% less at risk of dying than those on the placebo, but the difference wasn’t large enough to be significant. The drug also reduced the rate of lung infections and heart problems, but Glaxo said it couldn’t draw any solid conclusions from those secondary studies.

Still, the results are a blow to Glaxo. A positive result could have boosted sales of Breo by encouraging doctors to prescribe the drug over others in patients with higher cardiovascular risk. Breo is one of the drugs Glaxo is betting on to increase sales as its older blockbusters lose patent protection, but the drug’s market share hasn’t grown as quickly as expected because U.S. insurers have been slow to cover the drug.

Breo was launched in the U.S. in 2013 as a treatment for COPD. It later won approval from the Food and Drug Administration for use in adults with asthma. In Europe, where the product is known as Relvar Ellipta, the drug is used for COPD and asthma.

Glaxo has become a lower-margin company following its $20 billion asset swap with Novartis AG, in which it traded its highly profitable oncology franchise for the Swiss company’s vaccines business, which has slimmer margins. The pair also formed a joint venture, controlled by Glaxo, for their over-the-counter medicines, which also have lower margins than prescription pharmaceuticals.