HDL Mimetic Fails to Reduce Atherosclerosis in ACS: CHI-SQUARE

May 05, 2014

MONTREAL, QC – An HDL mimetic used in the treatment of patients with ACS failed to reduce the burden of atherosclerotic disease, a new study has shown[1].

The negative results of the phase 2b study, Can HDL Infusions Significantly Quicken Atherosclerosis Regression (CHI-SQUARE), have been known since Cerenis Therapeutics, the manufacturer of the HDL-mimetic agent, announced the topline results in January 2014, but the final results are now published online in the European Heart Journal.

Led by Dr Jean-Claude Tardif (Montreal Heart Institute, QC), the study was a prospective, double-blind, randomized trial conducted at 51 centers in the US, Canada, France, and the Netherlands. In total, 507 patients with ACS were randomized to receive six weekly injections of placebo or three doses (3, 6, or 12 mg/kg) of CER-001.

As previously reported by heartwire , CER-001 is an engineered lipoprotein particle than mimics pre-beta HDL. It consists of a combination of recombinant human apolipoprotein A1 (apoA1), the major structural protein of HDL, and two phospholipids. The hope had been that CER-001 could increase apoA1 and the number of HDL particles to accelerate reverse cholesterol transport and lower the atheroma burden.

Three weeks after the last infusion, the nominal change in total atheroma volume, as measured by intravascular ultrasound (IVUS), was not significantly different among those treated with placebo vs the three doses of CER-001. The percent change in atheroma volume was similar in all four treatment groups; neither of the changes in the CER-001 dose arms were significantly different from placebo. Quantitative coronary angiography analyses backed up the IVUS findings. In terms of CV events, there was no significant difference between CER-001 and placebo.

CHI-SQUARE is the latest in a string of HDL-raising studies that have failed to show a benefit. Trials with niacin and other studies with various investigational cholesteryl ester transfer protein (CETP) inhibitors have not shown a benefit on clinical outcomes despite raising HDL levels. At the American Heart Association 2013 Scientific Sessions, two HDL mimetics—CSL-112 (CSL Limited) and ETC-1002 (Esperion)—showed positive results in phase 2a studies. However, both studies were smaller than CHI-SQUARE and used biomarker end points.

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