MDCT and Leukotriene Inhibitor May Reduce Unstable Coronary Plaques

The results of a substudy of patients in an acute coronary syndrome (ACS) phase II trial who received serial 64-slice multidetector computed tomography (MDCT) scans before and after six months of treatment with a new drug, VIA-2291, an inhibitor of leukotrienes, (proposed mediators of vascular inflammation) demonstrated a reduction in noncalcified plaque volume and fewer new plaque lesions in treated patients.

Results of the study were presented at the American Heart Association Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) annual conference 2009 in Washington DC, USA, in May 2009, by Jean-Claude Tardif, M.D., of the Montreal Heart Institute (QC, Canada), and Dr. Rebecca Taub, VIA Pharmaceuticals, Inc. (San Francisco, CA, USA), senior vice president, research and development. VIA developed VIA-2291.

Of 191 patients enrolled in the first 12 weeks of the ACS trial, over 85 elected to continue in the study for an additional 12 weeks, receiving either placebo or VIA-2291 on top of current standard medical care. Each of these patients received an MDCT scan at baseline and at 24 weeks. Evaluable scans from patients treated with placebo showed significantly more evidence of new plaque lesions at follow-up than VIA-2291 treated patients. MDCT scans of patients with low-density plaques demonstrated statistically significant, lower plaque volumes in combined VIA-treated groups compared to placebo. Combined, these findings suggest that VIA-2291 may reduce the progression of unstable coronary plaques that lead to heart attacks and stroke.

In spite of recent advances in treatment, cardiovascular disease remains a leading cause of death and disability in the United States and the world. Emerging research points to the potential for inflammation within the vascular wall to be a key contributing factor in major adverse cardiac events (MACE) such as heart attack or stroke. This ACS substudy is the first clinical trial to use MDCT imaging to assess the effects of a drug on coronary plaque in a large patient cohort. MDCT is a state-of-the-art imaging technology that enables noninvasive imaging of coronary vessels.

"This innovative imaging technology has, for the first time, allowed us to visually and noninvasively demonstrate a reduction in plaque volume and a reduced number of new plaque lesions,” said Dr. Jean-Claude Tardif, director of the Montreal Heart Institute Research Center, professor of medicine at the University of Montreal and lead investigator of the VIA-2291 ACS trial. "In the ACS study results presented in 2008, we discussed VIA-2291's ability to reduce high sensitivity C-reactive protein [hs-CRP], a biomarker for inflammation. Taken as a whole, these results are an important step forward in understanding the importance of one cardiovascular inflammatory pathway.”

"VIA-2291 continues to show a significant effect on vascular inflammation, and these data add to the weight of the evidence from our phase II trial program,” said Lawrence K. Cohen, Ph.D., chief executive officer of VIA. "We have now combined histology, non-invasive imaging, and biomarker data to demonstrate the impact of VIA-2291. This adds support to our clinical development efforts and gives us even greater confidence as we look to move into a larger trial.”

VIA Pharmaceuticals is a biotechnology company focused on the development of compounds for the treatment of cardiovascular and metabolic disease. VIA's lead candidate, VIA-2291, targets a significant unmet medical need: reducing inflammation in the blood vessel wall, which is an underlying cause of atherosclerosis and its complications, including heart attack and stroke. Moreover, VIA's pipeline of drug candidates includes other compounds to address other underlying causes of cardiovascular disease: high cholesterol, diabetes and inflammation.

Related Links:
Montreal Heart Institute
VIA Pharmaceuticals