June 28th, 2013

More Bad News for HDL Therapies: ASSURE Trial Misses Primary Endpoint

The string of bad news for HDL-related therapies continues. Resverlogix yesterday announced that the ASSURE clinical trial had failed to meet its primary endpoint. RVX-208, the drug being studied in the trial, is a novel small molecule that increases production of Apolipoprotein A-I (ApoA-1), which raises HDL levels and is thought to enhance reverse cholesterol transport.

ASSURE was a phase 2b multicenter, double-blind, randomized, parallel group, placebo-controlled trial studying RVX-208 in 324 patients with coronary artery disease and low HDL levels. The company said the trial “did not meet its primary endpoint of a -0.6% change in percent atheroma volume as determined by intravascular ultrasound (IVUS). The RVX-208 treated group had -0.4% plaque regression (p=0.08).” The company reported that the trial did meet “the secondary endpoints of regression of total (coronary) atheroma volume (TAV) and increases in Apolipoprotein A-I (ApoA-I) and HDL cholesterol.” The company said that results in the placebo arm of the study were stronger than expected.

Full results of the trial are expected to be presented later this year. Earlier this month the company said the results may be presented at the European Society of Cardiology meeting in Amsterdam at the end of the summer.

ASSURE was run by the Cleveland Clinic. Steve Nissen is the chairman of the trial and Stephen Nicholls is the principal investigator.

In recent years the once-highly promising area of HDL-raising therapies has experienced a series of disappointments. Large trials with niacin (AIM-HIGH and HPS2-THRIVE) and CETP inhibitors (Pfizer’s anacetrapib and Roche’s dalcetrapib) have failed spectacularly. Some critics maintain that although the drugs in these trials raised HDL levels, they did not enhance the functional aspect of HDL. RVX-208 was intended to do just that. One remaining question about ASSURE is whether a 26-week study with an IVUS endpoint was actually capable of measuring the potential clinical benefits of the drug. IVUS has never been validated as a surrogate endpoint.





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