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 (IC50=0.035 microM) 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].