Schering-Plough bolsters late-stage cardiac pipeline

By Dr Matt Wilkinson

- Last updated on GMT

Related tags: Heart

Schering-Plough has licensed acadesine (AICA-riboside), a potential
first-in-class drug for the prevention of ischemia-reperfusion
injury from PeriCor Therapeutics to bolster its cardiac
therapeutics pipeline.

The deal will see Schering-Plough gain worldwide rights to the adenosine regulating agent (AGA) which is currently in Phase III trials. Financial details of the transaction, which is expected to close in the third quarter of 2007, were not disclosed. According to Fred Hassan, CEO of Schering-Plough: "Acadesine represents an important strategic opportunity to expand and strengthen our growing cardiovascular franchise…[and] further demonstrates our long-term commitment to developing treatments to address unmet needs in cardiac care."​ Ischemia-reperfusion injury is a serious, life-threatening cardiac surgery complication in patients undergoing coronary artery bypass graft (CABG) surgery by cardiopulmonary bypass for which there are currently no approved treatments. Cardiopulmonary bypass is a procedure that stops the heart and places the patient on a pump while the bypass is carried out. This leads to a dramatic shortage of oxygen in the heart, a condition known as ischemia which can lead to cell death if the oxygen supply is not returned within three or four hours. Restoration of the blood flow after an ischemic event can lead to the production of free radicals which cause inflammation and oxidative damage to the tissue and can be more damaging than the ischemic event itself. Indeed, according to a US national cardiac surgery database there is over a 13 per cent chance of complication or death after such an operation due to the condition. "There is a significant unmet medical need in preventing morbidity and mortality from ischemia-reperfusion injury following CABG surgery,"​ said Dr Rick Veltri, group vice president of 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."​ According to researchers from Gensia Pharmaceuticals, the initial inventors of the drug, adenosine is produced by the myocardium in response to ischemia to inhibit platelet aggregation and maintain the coronary arteries. The inhibition of platelet aggregation occurs via an adenosine A2-receptor-mediated stimulatory guanyl protein linked activation of adenylate cyclise that increases platelet cAMP. The researchers showed that while adenosine has a relatively short half-life, acadesine increases the amount of adenosine in the blood leading to protection of the myocardium during ischemia and reperfusion. The research, published in The Journal of Clinical Investigation​, showed that acadesine helps to inhibit platelet aggregation while not being a ligand for the adenosine A1 or A2 receptors. Other preclinical studies have shown that acadesine causes adenosine release in an event-specific and site-specific fashion and remains pharmacologically 'silent' in the absence of net ATP (adenosine triphosphate) breakdown. This lessens the shock of the reintroduction of blood flow and significantly reduces the chances of post-operative composite events such as cardiac death, myocardial infarction and stroke. A study published in the Journal of the American College of Cardiology​ showed that the risk of dying two years after CABG surgery was reduced by 77 per cent to 6.5 per cent in patients treated with acadesine compared to 27.8 per cent in the control group. At the time of the results, Richard Stover, CEO of PeriCor Therapeutics said: "The remarkable findings of this study confirm that adenosine regulating agents, of which acadesine is the prototype, represent a potentially unique and effective treatment to protect the heart muscle from ischemia-reperfusion injury." ​The promising nature of these results belies the drug's somewhat chequered past. In 1994, the US Food and Drug Administration (FDA) rejected Gensia's new drug application (NDA) after a Phase III trial failed to demonstrate significant efficacy. The company subsequently reorganised and spun-out Metabasis Therapeutics which inherited the ARA technology along with other programmes. The rights to the ARA technology then passed into the hands of PeriCor.

Related topics: Clinical Development, Phase III-IV

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