GSK Drug Fails in Heart Attack Trial

GlaxoSmithKline has posted top-line results from the Phase III trial of darapladib in adults with chronic coronary heart disease (CHD). The study did not meet the primary endpoint measure, which was time to first occurrence of any major adverse cardiovascular event (MACE) from the composite of myocardial infarction (heart attack), stroke, and cardiovascular death. There were greater reductions in some of the pre-defined secondary endpoints that require further analysis. Additional data will be forthcoming from the compound’s second Phase III study.

GSK plans to evaluate patient sub-groups for potential efficacy signals. Full results of the study will be submitted for presentation at a scientific meeting in 2014. The data from this study will contribute to any future regulatory submissions for darapladib. The overall safety profile showed no major imbalance in serious adverse events between the active and placebo groups.

Darapladib is a selective and orally active inhibitor of Lp-PLA2 (lipoprotein-associated phospholipase A2) currently being investigated as a potential agent for the reduction of cardiovascular events in patients with coronary heart disease. Lp-PLA2 is an enzyme that is found in blood and in atherosclerotic plaques. Atherosclerosis is characterized by the build-up of plaques of fat, cholesterol and other substances within the walls of arteries and is, in part, an inflammatory disease. When these plaques rupture they can block vital blood vessels, causing acute coronary syndromes (heart attacks) and strokes. Elevated Lp-PLA2 activity has been implicated in the development and progression of atherosclerosis.

This Phase III study was a randomized, placebo-controlled, double-blind, parallel group, multi-center, event-driven study in adults with chronic coronary heart disease. Patients were randomized to receive either 160mg darapladib or placebo in addition to standard of care. Standard of care could include a statin, aspirin and blood pressure medications. The study enrolled more than 15,000 patients across 39 countries and continued until 1,500 major adverse cardiovascular events had occurred.

The primary endpoint was the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary endpoints included major coronary events, total coronary events, individual components of MACE, and all-cause mortality.

The second Phase III study is evaluating the efficacy of darapladib in patients with acute coronary syndrome. That trial, which involves more than 13,000 patients in 36 countries, is ongoing and expected to end in 2014.