Public Release: 

AVANT Atherosclerosis Vaccine Raises HDL, Reduces Atherosclerosis In Vaccinated Animals

Kureczka/Martin Associates

Company Plans To Initiate Human Safety Studies Of The Investigational Vaccine This Summer

NEEDHAM, MA (April 19, 1999): A novel vaccine approach shows promise for raising high density lipoprotein (HDL) or "good" cholesterol levels, and preventing atherosclerosis, according to preclinical research presented today by scientists from AVANT Immunotherapeutics (Nasdaq: AVAN). Vaccinated animals demonstrated 35% higher blood HDL cholesterol levels and atherosclerotic lesions were reduced by approximately 40 percent (p<0.046) compared with controls. The AVANT scientists presented their work today at the Federation of American Societies for Experimental Biology (FASEB) Experimental Biology '99 Meeting in Washington, D.C.

"We are very pleased with these results, which clearly demonstrate the feasibility of our vaccine approach as a novel strategy for preventing or treating atherosclerosis," said Una Ryan, Ph.D., president and chief executive officer of AVANT Immunotherapeutics. "As a result, we are preparing to initiate human clinical safety studies with the vaccine this summer."

Atherosclerosis is a major underlying cause of heart attacks and stroke. AVANT's atherosclerosis vaccine works by eliciting antibodies that block the activity of cholesteryl ester transfer protein (CETP), a molecule that mediates the movement of cholesterol from HDL to low density lipoprotein (LDL), or "bad" cholesterol. Blocking CETP activity results in high levels of HDL. Elevated LDL cholesterol is a key risk factor for atherosclerosis; LDL is the major carrier of cholesterol to body tissues and so is closely implicated in atherosclerotic plaque formation. In contrast, a high HDL cholesterol level is associated with a reduced risk of coronary heart disease. In fact, medical studies have shown that the risk of coronary heart disease is increased by 2%-3% for every 1% decrease in HDL cholesterol.

In the reported experiments, AVANT researchers employed cholesterol-fed rabbits, an accepted and well established experimental model that has been used in the development of current cholesterol-lowering therapies, including the statins. The results showed that CETP-vaccinated rabbits exhibited significantly reduced CETP activity and changes in plasma lipoproteins. Moreover, CETP-vaccinated rabbits had higher concentrations of HDL cholesterol in their blood, and had significantly smaller areas of fatty streak lesions in their aortas than were exhibited by untreated control animals.

AVANT believes that inhibiting CETP has great potential to be a safe and effective strategy for preventing coronary artery disease. AVANT cites the existence of a well-studied human population in Japan which congenitally lacks functional CETP. Individuals with this genetic mutation have been observed to have high HDL levels and a low incidence of atherosclerosis, and to have otherwise normal health. AVANT hopes to show similar effects in normal individuals through vaccination.

Dr. Ryan said, "Currently there is no effective therapy for increasing blood HDL levels: diet and moderate exercise are ineffective, statins produce only a modest 5-7% increase in HDL cholesterol, and niacin has side effects that limit its use. In addition, patient compliance with cholesterol lowering drugs has been low, leading to their reduced usefulness. Thus we believe a vaccine approach to raising HDL, by which patients might receive treatment two to three times yearly, could offer significant benefits for reducing the risks of atherosclerosis and coronary artery disease. In addition, such a vaccine might expand the market for cholesterol-lowering therapies to people at somewhat lower health risk, for whom cholesterol-lowering drugs are not presently employed."

Atherosclerosis is a progressive condition leading to arterial blockage and reduced blood flow by fatty deposits called plaque on blood vessel walls. This condition significantly increases the risk of many forms of cardiovascular disease including heart attack, stroke and peripheral vascular disease. Atherosclerosis can also contribute to other serious health conditions such as hypertension and chronic kidney failure. The American Heart Association currently lists cardiovascular disease as a the number one cause of death in the United States, and experts estimate that 10 million Americans annually suffer from complications of atherosclerosis. Cardiovascular disease is similarly a major health problem in many other developed countries.


AVANT Immunotherapeutics, Inc. is engaged in the discovery, development and commercialization of products that harness the human immune response to prevent and treat disease. The Company's lead therapeutic program is focused on compounds that inhibit the inappropriate activity of the complement cascade, which is a vital part of the body's immune defense system. The Company is also engaged in the development of Therapore®, a novel system for the delivery of immunotherapeutics for chronic viral infections and certain cancers. The Company and its collaborators are developing vaccines using the proprietary adjuvants, Adjumer® and Micromer®, for the prevention of influenza, Lyme disease, and respiratory syncytial virus (RSV). In a further collaboration, the Company is developing an oral human rotavirus vaccine and is developing its own proprietary vaccine for the management of atherosclerosis.

Additional information on AVANT Immunotherapeutics, Inc. can be obtained through the Company's site on the World Wide Web:

Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: This release includes forward-looking statements which reflect AVANT's current views with respect to future events and financial performance. The words "believe," "expect," "anticipate," and similar expressions identify forward-looking statements. Investors should not rely on forward-looking statements because they are subject to a variety of risks, Uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to: (1) the ability to successfully complete development and commercialization of products, including the scope and results of preclinical and clinical testing; (2) the ability to successfully complete product research and further development including animal, pre-clinical and clinical studies; (3) changes in existing and potential relationships with corporate collaborators; (4) the time, cost and uncertainty of obtaining regulatory approvals; (5) the ability to obtain substantial additional funding; (6) the ability to develop and commercialize products before competitors; and (7) other factors detailed from time to time in filings with the Securities and Exchange Commission.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.