Elinogrel, a reversible P2Y12 receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events.

摘要

P2Y purinergic receptor subtypes are expressed on the surface of platelets and are vitally important for platelet function. Elinogrel (PRT-060128), a novel, direct-acting and reversible platelet P2Y12 receptor (P2Y12R) antagonist, is being developed by Portola Pharmaceuticals Inc and Novartis AG for the intravenous and oral treatment of acute coronary syndrome and prevention of secondary thrombotic events. In phase I clinical trials, elinogrel demonstrated a rapid and potent inhibition of ADP-mediated platelet response, even in patients with coronary artery disease who were deemed non-responsive to clopidogrel, the current standard-of-care therapy. The pharmacodynamic effects of single-dose elinogrel were completely reversed within 24 h of administration and elinogrel was well tolerated with no significant adverse events reported. The results of a phase II clinical trial in patients undergoing non-urgent percutaneous coronary intervention are highly anticipated because elinogrel will be the first P2Y12R antagonist to be available in both intravenous and oral formulations to facilitate a smooth transition from short- to long-term treatment. Unlike the currently available P2Y12R antagonists, which require hepatic transformation to an active metabolite and elicit irreversible effects on platelets, elinogrel directly inhibits the P2Y12R with a fast onset and offset and is therefore a promising candidate for cardiovascular protection.