Phase III Study of Heart Drug Darapladib Fails to Meet Primary Endpoint
Lp-PLA2 inhibitor equivalent to placebo in reducing coronary events
Disappointing results have been reported from a phase III trial of an investigational lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib (GlaxoSmithKline), in adults with acute coronary syndrome (ACS).
In the SOLID-TIMI 52 study, darapladib did not achieve the primary endpoint of a reduction of major coronary events compared with placebo when added to standard of care. The overall safety profile of darapladib showed no major safety concerns and was generally consistent with the safety data seen in a previously reported phase III study, STABILITY.
ACS consists of situations or events, including heart attack, where there is a sudden reduction of blood flow to the heart. The initial presentation by a patient with ACS results in a diagnosis of coronary heart disease (CHD).
The primary endpoint measure in the SOLID-TIMI 52 study was the time to first occurrence of any event from the composite of CHD, myocardial infarction (MI), and urgent coronary revascularization for myocardial ischemia.
The SOLID-TIMI 52 (Stabilization Of PLaques UsIng Darapladib – Thrombolysis In Myocardial Infarction 52) trial is the second of two event-driven phase III studies of darapladib in patients with CHD.
In November 2013, results were announced from the first study, STABILITY, which showed that darapladib did not achieve a statistically significant reduction in the primary endpoint of major adverse cardiovascular events (i.e., cardiovascular death, MI, and stroke) compared with placebo in patients with CHD.
In SOLID-TIMI 52, darapladib was evaluated as a long-term therapy in patients within 30 days of ACS. The randomized, placebo-controlled, double-blind, parallel-group study enrolled more than 13,000 patients in 36 countries. The study design was published in the October 2011 edition of the American Heart Journal.
Darapladib is a selective and orally active inhibitor of Lp-PLA2. Elevated Lp-PLA2 activity has been implicated in the development and progression of atherosclerosis. Lp-PLA2 is an enzyme that is found in blood and in atherosclerotic plaques. Atherosclerosis is an inflammatory condition characterized by the build-up of plaques of fat, cholesterol, and other substances within the walls of arteries. When these plaques rupture, they can block vital blood vessels, causing ACS (including heart attack) and strokes.
Source: GlaxoSmithKline; May 13, 2014.