MC-1 does not reduce cardiovascular and cerebrovascular events in phase 3 MEND-CABG II trial

February 25, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Winnipeg: A press release from the Medicure Inc. suggests that the phase 3 MEND-CABG II trial did not meet the primary efficacy endpoints of reduction in cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.

The phase 3, MEND-CABG II study (MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery) was designed to evaluate the benefit of MC-1 (a lead product of Medicure Inc.) used pre- and post-CABG, a novel cardioprotective drug in terms of improvements in cardiovascular and cerebrovascular outcomes. This study was conducted by Medicure in collaboration with Duke Clinical Research Institute and Montreal Heart Institute.

MC-1 (pyridoxol-5-phosphate) is a naturally occurring metabolite of pyridoxine and is formed in the mammalian cells by phosphorylation and oxidation reactions. It blocks the intracellular influx of calcium and thereby reduces cell damage during ischemia and reperfusion.

This drug has been studied during percutaneous coronary intervention (PCI) and in phase 2 trial during coronary artery bypass surgery (CABG). Administered orally in the setting of PCI, MC-1 (250 mg) significantly reduced the release of CK-MB and myocardial ischemia measured using continuous ST segment monitoring following PCI (see link below-1). This randomized, placebo controlled blinded study consisted of 60 patients.

The phase 2, CABG trial demonstrated that there was no impact on the primary endpoints at 30 days (cardiovascular death, nonfatal myocardial infarction and nonfatal cerebral infarction) using MC-1. However, there was a significant reduction in the post-operative CK-MB (70-100 ng/ml) release with MC-1 group compared to the placebo group. This study consisted of a total of 901 patients.

The results of the phase 2 trial led to the phase 3 study consisting of over 3000 patients from over 130 centers in North America and Canada undergoing CABG. According to the press release (see link below-2) that was published on 22 February, there was no benefit in terms of reduction in cardiovascular deaths, nonfatal myocardial infarction and nonfatal cerebral infarction at 30 days following CABG using MC-1 compared to placebo. The press release also notes that the results of the phase 3, MEND-CABG II trial will be presented at the forthcoming Annual Scientific Sessions of the American College of Cardiology 2008 in Chicago.

Further information can be obtained on the web pages of Medicure http://www.medicure.com