Clinical Trial Showed Reduced Inflammation In Cardiovascular Patients
Montreal Heart Institute Research Centre Director Dr. Jean-Claude Tardif presented yesterday results from a clinical trial demonstrating that VIA-2291, an investigational drug being developed by VIA Pharmaceuticals, Inc., significantly inhibited production of leukotrienes, proposed mediators of vascular inflammation, in patients with serious heart disease. VIA-2291 was well-tolerated with no serious adverse events attributed to the drug. The study was presented in a Special Session at the American Heart Association 2008 Scientific Sessions in New Orleans, Louisiana.
The study of VIA-2291 was designed to establish optimal dosing and safety data in patients with acute coronary syndromes (ACS), who recently had a heart attack or unstable angina. 191 patients were treated once daily for 12 weeks with one of three dose levels of VIA-2291 or placebo. A sub-study of patients continued for an additional 12 weeks of treatment.
Cardiologists have several therapies that help reduce heart disease risk factors, but none that specifically target inflammation, an underlying cause of atherosclerosis, which leads to major adverse cardiac events (MACE), including heart attack and stroke.
VIA-2291 is designed to be a selective and reversible inhibitor of 5-LO, a key enzyme in the biosynthesis of leukotrienes, that are important mediators of inflammation believed to be involved in the development and progression of atherosclerosis.
"VIA-2291 has the potential to be the first drug to specifically target one cardiovascular inflammatory pathway," said Dr. Jean-Claude Tardif, the VIA-2291 ACS trial's principal investigator, director of the Montreal Heart Institute Research Centre and professor of medicine at the Universite de Montreal. "These data support further clinical development of this drug, including larger outcome trials."
The trial demonstrated a statistically significant, dose-dependent inhibition of Leukotriene B4 (LTB4) production at 12 weeks. The secondary endpoint of change from baseline in urine Leukotriene E4 (LTE4) also showed significant inhibition at all dose levels.
A statistically significant reduction from baseline as compared to placebo was observed in high-sensitivity C-reactive protein (hs-CRP) levels in the highest dose group of patients treated for 24 weeks. Significant reductions in hs-CRP levels were not observed in the ACS trial in patients treated for 12 weeks, perhaps due in part to variability in the level of hs-CRP at the baseline as a result of recent heart attack or unstable angina.
About Atherosclerosis and Inflammation
Atherosclerosis is the result of chronic inflammation and the build-up of plaque in arterial blood vessel walls. Plaque consists of inflammatory cells, cholesterol and cellular debris. Atherosclerosis, depending on its severity and the location of the artery it affects, may result in blockage in certain vessels and can cause a rupture of inflamed plaque tissue, leading to MACE such as heart attack and stroke, which are leading causes of death worldwide.
VIA-2291 is designed to complement current standard of care therapies that treat cardiac risk factors, such as statins, antiplatelet and blood pressure medications. VIA-2291 is initially targeted to address the secondary prevention market for patients who have already suffered a major adverse cardiac event, but eventually could be beneficial to the broader 15.8 million patients in the U.S. who have coronary artery disease. VIA-2291 has been tested in more that 1,300 patients in clinical trials.