Kenilworth, NJ - A major phase 3 development program has been announced for Schering-Plough's new oral antiplatelet agent, involving two of the most prominent clinical-trial centers in the US [1].

The product, known as TRA-SCH 530348, is the first of a new class of agents. It blocks the platelet PAR-1 receptor to which thrombin binds, thus inhibiting thrombin-induced activation of platelets, and is therefore classified as a thrombin-receptor antagonist (TRA).

In a phase 2 trial, reported at the American College of Cardiology meeting last month, the compound showed a trend toward fewer ischemic events without increasing bleeding when added to standard antiplatelet therapy with aspirin and clopidogrel in patients undergoing PCI. If phase 3 trials confirm that the drug does actually reduce ischemic events without increasing bleeding, TRA-SCH 530348 would be a surefire winner. But that is a big if, and many previous drugs have shown promising results in phase 2 trials that have not been borne out in larger studies.

Two major phase 3 trials with TRA-SCH 530348 are now planned, one for the treatment of acute coronary syndrome (ACS) patients, and one for secondary-prevention in patients who have had a prior MI or stroke or who have existing peripheral arterial disease. In both trials, TRA-SCH 530348 will be compared with placebo, and all patients will be taking standard antiplatelet therapy (including aspirin and clopidogrel). The trials will be conducted in approximately 30 countries at more than 800 sites for each trial.

The ACS trial will involve approximately 10 000 patients. TRA-SCH 530348 will be given once daily with a 40-mg oral loading dose and a 2.5-mg oral maintenance dose. The primary end point is the composite of cardiovascular death, MI, rehospitalization for ACS, urgent coronary revascularization, or stroke. Patients will be followed for a minimum of one year. This trial is being conducted by the Duke Clinical Research Institute under the leadership of Dr Robert Harrington.

The secondary prevention study, known as the TRA 2P-TIMI 50 trial, will involve approximately 19 500 patients with prior MI or stroke or existing peripheral arterial disease. This trial will evaluate a 2.5-mg daily maintenance dose of the drug. The primary end point of the trial is the composite of cardiovascular death, MI, urgent coronary revascularization, or stroke. Patients will be followed for a minimum of one year. This trial is being conducted by the TIMI Study Group, chaired by Dr Eugene Braunwald (Harvard Medical School, Boston, MA).

Schering-Plough notes that the FDA has granted fast-track designation to TRA-SCH 530348, which allows expedited review of drugs and biologics for serious or life-threatening conditions that demonstrate the potential to address unmet medical needs.