FDA Approves Merck's Zontivity For Reduction Of Thrombotic Cardiovascular Events

Merck announced in a press release that the Food and Drug Administration (FDA) has approved Zontivity (vorapaxar). An antiplatelet agent is indicated for the reduction of thrombotic cardiovascular events in patients with a history of heart attack (myocardial infarction) or in patients suffering from peripheral arterial disease (PAD). Zontivity was not studied for monotherapy, only as an addition to aspirin and/or clopidogrel. The new drug will be available in the third quarter of 2014.

Ellis Unger, director of the Office of Drug Evaluation in the FDA’s Center for Drug Evaluation and Research said, “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. In the study that supported the drug’s approval, Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year.

Zontivity

Zontivity (vorapaxar) is an antiplatelet agent and the first to work on the protease-activated receptor-1 (PAR-1) pathway. This pathway helps form platelets and blood clots. Zontivity inhibits PAR-1 and thrombin, stopping platelet activation. Since aspirin or clopidogrel does not target the PAR-1 pathway, Zontivity addresses the pathway, making the combination therapy more effective. Patients take the drug once daily in a 2.08 mg vorapaxar dose. Zontivity is not indicated for patients with active bleeding, a history of stroke, or intracranial hemorrhage (ICH). The FDA in its press release about the approval said that health providers should warn patients of the possibility of increased bleeding and bruising. 

Clinical Trials

Zontivity was studied in over 25,000 patients, and results showed a reduced rate of heart attack, stroke, coronary revascularization, and cardiovascular death compared to a placebo. The TRA 2°P TIMI 50 trial (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events) was one of the largest studies of an antiplatelet medicine. In the secondary endpoint of risk reduction, Zontivity reduced risks by 20 percent for CV death, MI, and stroke. Investigators followed patients up to four years, with an average follow-up time of two and one half years. Results showed that a combination of Zontivity and either aspirin or clopidogrel was superior to just aspirin or clopidogrel alone.