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Atherosclerosis Drug Fails to Meet Primary Endpoint in Phase II Trial
In a phase IIb study, the investigational atherosclerosis compound RVX-208 (Resverlogix Corp.) — an orally active bromodomain and extra-terminal (BET) protein inhibitor — did not meet its primary endpoint of a –0.6% change in percent atheroma volume, as determined by intravascular ultrasound, in high-risk cardiovascular patients with low high-density lipoprotein (HDL) levels. Patients treated with RVX-208 showed –0.4% plaque regression (P = 0.08).
However, patients receiving active treatment met the secondary endpoints of regression of total (coronary) atheroma volume and increases in apolipoprotein A-I (ApoA-I) and HDL cholesterol.
The phase IIb ASSURE trial — a 26-week, double-blind, randomized, parallel-group, placebo-controlled study — enrolled 324 patients and was led by the Cleveland Clinic. The trial’s secondary endpoints included the safety and tolerability of RVX-208, and the effects of the compound on plasma apoA-I, HDL cholesterol, HDL subclasses, and non-HDL lipid parameters.
According to the compound’s developer, RVX-208 is a small molecule that inhibits BET bromodomains. RVX-208 functions by removing atherosclerotic plaque via reverse cholesterol transport (RCT), the natural process through which atherosclerotic plaque is transported out of the arteries and removed from the body by the liver. In addition, RVX-208 increases the production of apoA-I, the key building block of functional HDL particles and the type required for RCT. These newly produced, functional HDL particles are flat and empty, and can efficiently remove plaque and stabilize or reverse atherosclerotic disease. ApoA-I may also exert beneficial effects in Alzheimer’s disease and diabetes mellitus.
Source: Resverlogix Corp.; June 27, 2013.