Panel Supports Prasugrel Approval With Few Conditions

SILVER SPRING, MD. — With unanimous support by an expert panel of prasugrel, the Food and Drug Administration is poised to approve the antiplatelet drug for treating patients with acute coronary syndrome who present with unstable angina, non-ST-segment elevation myocardial infarction, or ST-elevation MI.

All nine voting members of the FDA's Cardiovascular and Renal Drugs Advisory Committee agreed that prasugrel, a thienopyridine developed by Eli Lilly & Co. and Daiichi Sankyo Inc., has a favorable benefit-to-risk profile, based on clinical trial data.

Prasugrel, given as a 60-mg loading dose followed by 10 mg/day, was compared with clopidogrel, administered at a 300-mg loading dose followed by 75 mg/day, in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38), an international double-blind study of 13,608 patients with moderate to high-risk ACS, scheduled to have percutaneous coronary intervention. They had unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or STEMI. All patients were on aspirin.

Over a mean of 12 months, the primary end point—a composite of cardiovascular death, MI, or nonfatal stroke—occurred in 12.1% of patients on clopidogrel and 9.9% of those on prasugrel, a significant reduction.

The rate of strokes in both groups was 0.9%. The overall risk of cardiovascular death was also not significantly different between the two groups.

The main risk was bleeding. The rate of major bleeding was 2.2% in those on prasugrel, compared with 1.7% in those on clopidogrel; the rates were 1.3% and 0.8% for life-threatening bleeding, including fatalities; 0.3% and 0.1% for fatal bleeding; and 0.3% and 0.2% for intracranial hemorrhage.

An FDA analysis showed that for every 1,000 patients with ACS treated with prasugrel, the treatment prevents 21 nonfatal MIs and 3 cardiovascular deaths, with no strokes, but at a cost of 2 fatal hemorrhages, 3 nonfatal major hemorrhages, 5 minor hemorrhages, and 19 minimal hemorrhages.

All panelists agreed that labeling should discourage physicians from prescribing prasugrel to treat patients with a history of stroke or TIA.

Among patients over age 70 years, bleeding was not more common with prasugrel, but the sequelae were more serious. The company has proposed that a lower dose be used in patients over age 75 years, and in people who weigh less than 60 kg, who also were at a greater risk of hemorrhage.

The panel recommended that the drug not be taken around the time of CABG.

The FDA usually follows the recommendations of its advisory committee. If approved, prasugrel will be marketed as Effient.