Schering-Plough Corporation has announced the worldwide licensing of acadesine, an investigational, potentially first-in-class adenosine regulating agent (ARA), from PeriCor Therapeutics, Inc., a privately held, specialty biopharmaceutical company.
Acadesine is currently under evaluation in Phase III clinical development as an intravenous infusion for the prevention of ischemia-reperfusion injury, a complication of cardiac surgery in patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (a procedure that stops the heart and places the patient on a pump). Financial terms of the transaction were not disclosed. The transaction is expected to close in the third quarter subject to certain conditions to closing.
Ischemia-reperfusion injury represents a serious and life-threatening cardiac surgery complication in patients undergoing coronary artery bypass surgery performed with cardiopulmonary bypass, and there are currently no approved treatments. Although CABG surgical techniques have improved and reduced procedural morbidity and mortality, complication rates resulting from these procedures, such as ischemia-reperfusion injury, remain unacceptably high. According to a national cardiac surgery database from the Society of Thoracic Surgeons, there is a 30-day operative mortality and major complication rate of 13.4 percent associated with the CABG procedure (Ann Thorac Surg 2003;75:1856-1865).
"Acadesine represents an important strategic opportunity to expand and strengthen our growing cardiovascular franchise," said Fred Hassan, chairman and chief executive officer, Schering-Plough. "With the thrombin receptor antagonist, TRA or SCH-530348, our novel investigational antiplatelet medication in late-stage development; the Merck/Schering-Plough cholesterol- lowering products VYTORIN and ZETIA; and INTEGRILIN, the leading GP IIb-IIIa inhibitor, acadesine further demonstrates our long-term commitment to developing treatments to address unmet needs in cardiac care."
CABG surgery is a recommended treatment for high-risk patients who have coronary artery disease or previously experienced an ischemic event, such as a myocardial infarction (heart attack) or unstable angina, according to the guidelines of the American Heart Association and the American College of Cardiology.
Ischemia-reperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood creates a condition in which restoration of circulation results in inflammation and oxidative damage rather than restoration of normal function.
"There is a significant unmet medical need in preventing morbidity and mortality from ischemia-reperfusion injury following CABG surgery," said Rick Veltri, MD, Group Vice President, Global Clinical Development, Cardiovascular and Metabolic Diseases, Schering-Plough Research Institute. "Acadesine has the potential to reduce perioperative complications in this patient population, as well as decrease the burden of costs on the healthcare system," he added.
In a meta-analysis of five randomized trials of acadesine, there was a statistically significant 26 percent reduction in composite events (cardiac death, myocardial infarction, and stroke) in patients undergoing CABG (p=0.01) (JAMA 1997; 277:325-332). Acadesine therapy was also shown to reduce the severity of acute post-reperfusion MI, substantially reducing the risk of dying over the 2 years after the infarction by 4.3-fold, from 27.8 percent in the control group to 6.5 percent in the acadesine group (p=0.006) (JACC 2006; 48:206-14). The incidence of adverse events was similar in the acadesine and placebo groups, with the exception of a transient increase in serum uric acid.
An additional randomized, placebo-controlled Phase III trial will further evaluate acadesine in high-risk patients. High-risk patients are defined as either females, or males with a previous history of CABG surgery or cardiovascular events, such as heart attack or stroke. An agent that can be shown to reduce surgical complications can potentially have a significant impact on healthcare costs, since treated patients may be less likely to experience subsequent death, heart attacks, or strokes. The total cost for care of an average CABG patient in the US is approximately $60,000 per case (Am J Manag Care. 2004; 10:S370-S376).