Xemilofiban Searle and Co

Xemilofiban is an orally-active antiplatelet agent (GPIIb/IIIa receptor antagonist) under development by Searle for the potential use in preventing thrombotic complications, following percutaneous transluminal coronary angioplasty (PTCA). It is in phase III clinical trials in the US for thrombosis and phase I trials in Japan for peripheral vascular disease. The potential cardiovascular benefits of xemilofiban are being evaluated in a worldwide, phase III trial, EXCITE (Evaluation of oral Xemilofiban in Controlling Thrombotic Events). Approximately 7200 patients who are undergoing angioplasty or stent placement will be enrolled. The trial will assess whether six months of treatment will reduce clot-related cardiac events, such as heart attack and death, and the need for revascularization procedures 268912]. Results of the phase II ORBIT trial in 549 angioplasty patients, demonstrated that four-week therapy with xemilofiban inhibited platelet aggregation by 50 to 80% 268911]. Phase I studies in Japan were completed in patients undergoing coronary revascularization, including stents and PTCA, for acute myocardial infarction (AMI) and for unstable angina 182809]. Sankyo is conducting the development in Japan, under a license agreement 181803]. Xemilofiban has been included in the ISIS-6 trial which will evaluate its efficacy and safety in heart attack patients following thrombolysis 182809]. Preliminary studies have shown that oral xemilofiban produces a rapid inhibition of ADP and collagen-induced platelet aggregation 182809]. Its mechanism of action results in potent inhibition of platelet aggregation in response to all stimuli. It acts as the ethyl ester prodrug of SC-54701, which is a potent (IC(50) = 0.035 mM) and selective inhibitor of GPIIb/IIIa. Xemilofiban is expected to be launched in 2000 for angioplasty, and a year later for unstable angina and AMI 220816].