Acadesine: AICA riboside, ARA 100, arasine, GP 1 110

Acadesine is an adenosine receptor agonist (ARA) in development for the treatment of ischaemia-reperfusion injury and chronic lymphocytic leukaemia. Schering-Plough is developing the compound as a cardioprotective agent in ischaemia-reperfusion injury. Avancell and Protherics are co-developing acadesine for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL). Clinical development is underway for both indications. In January 2005, PeriCor Therapeutics obtained a sublicense for the worldwide rights to acadesine and three additional ARA compounds from Dr Mangano who was a founder of the company. Dr Mangano acquired the license of worldwide rights for acadesine from Metabasis in November 2000.Previously, in December 1997, all intellectual property rights and data covering acadesine and related ARAs for cardiovascular and cerebrovascular disorders were transferred from the original developer, Gensia Sicor (SICOR), to Metabasis Therapeutics in an asset-liability transfer agreement.Schering-Plough intends to conduct a randomized, placebo-controlled phase III trial, which is required for regulatory approval. The trial will further evaluate acadesine in patients deemed to be at high risk of ischaemic heart disorders. Patients will have either undergone coronary artery bypass graft surgery, or have a history of cardiovascular events (heart attack or stroke). Protherics presented 2-year mortality results from a study of acadesine, investigating long-term mortality after perioperative myocardial infarction, at the 55th Scientific Session of the American College of Cardiology in 2006.Previously, Gensia Sicor conducted clinical trials of acadesine in Canada, the EU and the US; results of these trials were inconclusive. Acadesine has been shown to selectively cause the death of B-cells, whilst sparing T-cells when administered to blood samples taken from patients with B-CLL. Orphan drug status has been granted for acadesine in the EU for the treatment of B-cell chronic lymphocytic leukaemia.