May 8th, 2014
Novel Antiplatelet Agent Vorapaxar Gains FDA Approval
The FDA today approved vorapaxar (Zontivity), Merck’s once-troubled platelet receptor antagonist, to reduce the risk of myocardial infarction (MI), stroke, cardiovascular death, and revascularization procedures. The drug is approved for use in people with a history of MI or peripheral arterial disease. The approval represents an amazing turnaround for a drug that has experienced nearly as many ups and downs as an amusement park roller coaster.
Vorapaxar is the first in a new drug class known as protease-activated receptor-1 (PAR-1) antagonists. By preventing the ability of platelets to stick together and form blood clots, the drug can help prevent MI and stroke. But it also increases the risk of bleeding, including life-threatening and fatal bleeding. Because the risk of serious intracranial bleeding is especially high in people who have had a stroke, a transient ischemic attack, or bleeding in the head, use of the drug is contraindicated in these groups. The drug’s label includes a boxed warning about the risk of bleeding. The FDA said the drug will be dispensed with a patient Medication Guide.
Vorapaxar appeared to be all but dead a few years ago after unacceptably high serious bleeding rates were found in two large clinical trials. But hopes for the drug resurfaced with a new analysis of one of those trials, the TRA2P trial. In a statement to the press, Ellis Unger, director of the FDA’s Office of Drug Evaluation I, said that the trial showed that “in patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death… Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year.”
In January the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-1 in favor of approval for vorapaxar.