Mutant HDL protein reduces plaque volume in ACS patients

Shelley Wood

June 30, 2003

Mon, 30 Jun 2003 14:00:00

Ann Arbor, MI - A phase 2 trial of an agent that mimics the transport of excess cholesterol and other lipids from arterial walls has demonstrated that patients who received the agent had significant regression of atherosclerosis. Esperion Therapeutics Inc, which developed the product, announced the preliminary results in a press statement June 26, 2003.

The agent, ETC-216, or apolipoprotein (apo)A-I Milano/phospholipid complex (AIM), is being tested in two doses in 47 patients with ACS awaiting coronary angiography. Dr Steven Nissen (Cleveland Clinic, OH), principal investigator of the multicenter study, confirmed that the early results were "very promising" but declined to say more, stating that the study was under expedited review by a peer-reviewed journal.

From a village in Italy

The study is a randomized, double-blind, placebo-controlled trial evaluating two different infusions of ETC-216: 15 mg/kg or 45 mg/kg administered every seven days to a maximum of five doses. The primary end point of the study was change in percent plaque volume for patients in the combined ETC-216 treatment arms as measured with IVUS. The only result released by the company so far, as stipulated by securities' regulations, was that the study had reached its primary end point.

The idea for the agent being tested came from a small Northern Italian village, where a small proportion of the villagers were found to have extremely low HDL cholesterol but, paradoxically, long life expectancy and very low rates of cardiovascular disease. Further research, much of it led by Dr Prediman K Shah (Cedars-Sinai Medical Center, Los Angeles, CA), during the mid-1990s led to the discovery of apoA-I Milano, a mutant form of apoA-I found in the Italian group, in which one of the protein's amino acids is replaced with the amino acid cysteine. Building on the understanding that apoA-I Milano appears to facilitate enhanced reverse lipid transport, the company developed ETC-216/AIM, a recombinant protein that investigators say can reduce atherosclerotic burden in animal and human arteries.


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