Esperion Therapeutics, Inc announced the results of a study providing significant evidence that its investigational product candidate, ETC-216, rapidly reduced the size of plaque in coronary arteries and reversed atherosclerosis. The results of the study appear in the November 5, 2003 issue of the Journal of the American Medical Association (JAMA). The study is the first clinical evidence that atherosclerosis, a progressive disease resulting from deposits of fatty substances such as cholesterol in the artery walls, can be rapidly reversed.

"These results demonstrate for the first time that it is possible to rapidly regress the major underlying cause of heart attack," said Roger S. Newton, Ph.D., president and CEO of Esperion Therapeutics. "By enhancing the removal of cholesterol from plaques in artery walls, a process known as reverse lipid transport, HDL therapy may provide an innovative approach to the treatment of atherosclerosis. We are excited about these results and look forward to continuing the development of ETC-216 in more patients with longer follow-up and assessing more endpoints, including morbidity and mortality."

In the phase 2 clinical trial, 47 patients with acute coronary syndromes (ACS) received five weekly intravenous infusions of placebo, ETC-216 at 15 mg/kg and ETC-216 at 45 mg/kg. Plaque volume was measured before treatment and within two weeks after the final infusion using intravascular ultrasound (IVUS). With IVUS, a tiny ultrasound probe is inserted into the coronary artery to directly image and measure the size of the atherosclerotic plaques. The study revealed a statistically significant reduction (p=0.02) in per cent atheroma (plaque) volume in the combined ETC-216 treatment groups comparing end-of-treatment values to baseline values.

Additional IVUS endpoints in the trial, such as total atheroma volume and maximum atheroma thickness, also showed statistically significant improvements.

"This study shows that ETC-216 could become an important new option for the treatment of people affected by atherosclerosis," said Steven E. Nissen, M.D., FACC, principal investigator of the study and medical director of the Cleveland Clinic Cardiovascular Coordinating Center. "We now have evidence that it is possible to rapidly and directly reverse the atherosclerotic disease process in artery walls."

Of the 57 patients assigned to a treatment group, 47 patients completed the trial. Of the ten patients who did not complete the trial, two were withdrawn for an adverse event, three withdrew consent and five had IVUS studies that were not analyzable. Overall adverse event rates were similar in all three treatment groups and ETC-216 was generally well tolerated.

Special carriers called lipoproteins transport cholesterol in the bloodstream. Low-density lipoprotein (LDL), often referred to as "bad" cholesterol, transports cholesterol to the body's cells. High levels of LDL cholesterol can lead to the build-up of cholesterol and other fats in the walls of arteries. These deposits can eventually form a plaque. If a plaque ruptures and a clot forms and blocks an artery, it can cause a heart attack. High-density lipoprotein (HDL), often referred to as "good" cholesterol, is believed to remove cholesterol and other lipids from artery walls and other tissues and transport them to the liver where they are eliminated from the body.

ApoA-I Milano is a variant of ApolipoproteinA-I (ApoA-I), the major protein component of HDL. ApoA-I Milano is present in a small population of northern Italians with paradoxically low levels of HDL-cholesterol. Low HDL cholesterol levels normally would correlate with high risk for cardiovascular disease, but carriers of the ApoA-I Milano gene show a reduced risk, presumably due to enhanced reverse lipid transport (RLT), the body's process of removing excess cholesterol and other lipids from artery walls and other tissues and transporting them to the liver for elimination. ETC-216 (AIM) is a human recombinant version of ApoA-I Milano combined with a phospholipid to form a complex that imitates the structure and function of HDL. ETC-216 is designed to mimic the beneficial properties of HDL and enhance RLT.

According to the American Heart Association, more than 60 million Americans have some form of cardiovascular disease. It is the leading cause of death in the United States, claiming the lives of nearly one million Americans each year.