ORBIT Data Support Phase III Studies Of Xemilofiban

Searle's xemilofiban is in the forefront of the new orally-activeglycoprotein IIb/IIIa inhibitors coming through development for use in acute coronary settings. At the 70th Scientific Sessions of the American Heart Association, data were presented from ORBIT, the first Phase II trial of xemilofiban, which indicates that the drug is safe, well-tolerated and inhibits platelet aggregation between 50% and 80%.

The non-peptidic, orally-bioavailable gpIIb/IIIa inhibitors have been developed to see if maintaining potent platelet inhibition over several months can reduce cardiac events after a coronary intervention better than aspirin, which has been shown to cut these events by around 25%, despite being a relatively weak antiplatelet drug. More potent antiplatelet agents such as Sanofi's Tiolit (ticlopidine) and Sanofi and Bristol-Myers Squibb's Plavix (clopidogrel) have improved on aspirin, but the most dramatic gains have been achieved using the parenteral antibody-based gpIIb/IIIa inhibitor, Centocor/Eli Lilly's ReoPro (abciximab).

Intravenous abciximab administered over a period of several hours or days has shown significant reductions of events at 30 days post-intervention. Unfortunately, its route of administration limits the duration of antiplatelet therapy to the time the patient is in hospital, and the CAPTURE study has shown that the benefit tails off after ReoPro is discontinued. It is hoped that oral gpIIb/IIIa inhibitors such as xemilofiban can be used to improve outcome further by allowing longer-term platelet inhibition.