Acadesine in CABG Surgery
In August 2007, we granted a license to Schering-Plough Corporation for global development and commercialization of acadesine for all indications. They will conduct a Phase IIIB clinical trial to confirm acadesine's safety and efficacy in reducing the composite incidence of all-cause mortality, severe left ventricular dysfunction, and stroke in patients undergoing CABG surgery.
Clinical experience with acadesine in CABG surgery documents unique cardioprotective benefit in the setting of ischemia-reperfusion injury and a very favorable safety profile of this novel mechanism of action of our ARA platform. Acadesine has been studied in placebo-controlled Phase II-III clinical trials enrolling over 4,000 patients undergoing CABG surgery. CABG surgery produces extreme conditions of physiologic trespass and reperfusion injury that involve the complete occlusion of coronary flow lasting 30 minutes or longer. Because it requires induced, protracted ischemia which is followed by reperfusion, CABG surgery constitutes a robust human model for the risks associated with reperfusion injury.
A by-patient meta-analysis of five placebo-controlled clinical trials in CABG surgery showed that acadesine treatment as compared to placebo resulted in a 27% reduction in the incidence of perioperative myocardial infarction (p=0.025), a 50% reduction in the incidence of cardiac death (p=0.042) and a 26% reduction in the composite incidence of adverse perioperative cardiovascular events (p=0.015) that included heart attack, cardiac death and stroke.
Acadesine’s unique effect in mitigating the effects of reperfusion injury was demonstrated in a study entitled “Post-Reperfusion Myocardial Infarction, Long-Term Survival Improvement Using Adenosine Regulation with Acadesine,” that was published in July 2006 by the Journal of the American College of Cardiology. This study investigated the effects of acadesine on two-year survival following a perioperative heart attack among the 2,700 patients enrolled in the earlier Phase IIIa, in-hospital 1024 trial. Importantly, this long-term follow-up trial showed that:
- Among placebo-treated patients, a perioperative MI imposed a 7-fold increase in mortality at two years (p=0.001)
- Acadesine treatment virtually eliminated the excess mortality risk of a perioperative MI: perioperative administration of acadesine treatment resulted in a 77% reduction in two-year post-MI mortality as compared to placebo-treated patients (p=0.004)
The Lethality of Perioperative MI is Largely Negated by Acadesine Treatment