The FDA Gives Merck's Vorapaxar A Positive Review
By Cyndi Root
The Cardiovascular and Renal Drugs Advisory Committee, a Food and Drug Administration (FDA) committee, voted to approve Vorapaxar in a 10 to 1 vote. The drug, sponsored by Merck Sharp & Dohme Corp., Inc., is for patients with Myocardial Infarction (MI). The FDA can reject or accept the committee’s recommendation, but the agency takes the committee’s advice seriously, and in most cases issues final approval. If the new drug is approved, Merck plans to market it as Zontivity.
Vorapaxar is a thrombin receptor antagonist. The drug stops the protease-activated receptor-1 (PAR-1) from being activated by thrombin. This antagonistic mechanism stops platelets from clumping in the arteries. Clumping platelets lead to cardiovascular events like heart attacks. Dr. Daniel Bloomfield, Vice President of Cardiovascular Diseases at Merck Research Laboratories said, “The results of today’s Advisory Committee mark an important milestone in our effort to bring Vorapaxar to appropriate patients with a history of heart attack.”
The FDA published an Advisory Committee Briefing detailing Merck’s New Drug Application (NDA). Merck applied to use an oral dose of Vorapaxar at 2.5 mg daily for patients with a history of MI. Merck relied on data from a clinical trial to support its assertion that the drug reduces atherothrombotic events. The clinical trial was called, “Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Events (TRA 2°P-TIMI 50) trial”. In the trial, patients with a history of MI benefited the most, as long as no history of transient ischemic attack (TIA) or stroke was present.
The Merck application sought a specific indication from the committee. The company wanted affirmation that for patients with MI, Vorapaxar is an antagonist of PAR-1, is indicated to reduce atherothrombotic events, and is shown to reduce stroke, cardiovascular death, and urgent coronary revascularization. Merck acknowledged in the application that Vorapaxar is contraindicated in patients with intracranial hemorrhages, pathological bleeding, and those with a history of stroke.
Committee members had some concerns about bleeding risks, but were convinced of the drug’s efficacy for a specific population—those with MI, but not those with prior strokes. The committee did not recommend that Merck establish follow-up management studies or perform additional clinical trials.