Sibrafiban (RO 483657, RO 483657-001, XubixTM) is a double oral prodrug that undergoes conversion to the inactive prodrug RO 483656, which in turn is metabolised to the potent, nonpeptide glycoprotein IIb/IIIa receptor antagonist RO 443888. Sibrafiban appears to be well tolerated in animals and produces dose-dependent effects on platelet aggregation and template bleeding times.
Sibrafiban is under development with Roche, while Genentech has retained option rights for the product. It is being developed worldwide for the prevention of secondary events in patients following acute coronary syndromes, including unstable angina pectoris or myocardial infarction. A phase III study (the SYMPHONY trial) is being conducted worldwide in 9000 patients stabilised after a myocardial infarction or unstable angina pectoris. A twice daily dosage regimen is to be used. A long term study (2nd SYMPHONY) is also underway and will continue for a minimum duration of 12 months and recruit about 8400 patients. The dosages used in both studies were determined in the TIMI 12 study and achieve plasma RO 443888 levels of between 7 and 40 μg/L.