The FDA's Cardiovascular and Renal Drugs Advisory Committee today voted 6-4, with one abstention, against approval of rivaroxaban for use in acute coronary syndrome.
Panel members highlighted a lack of data on early patient withdrawals and deaths as a major issue. In fact, Philip Sager, MD, pharmaceutical consultant and chair of the Cardiac Safety Research Consortium, said these missing data are what concerned him the most.
The committee discussed data from the global, phase 3 ATLAS ACS 2 – TIMI 51 study and vote whether rivaroxaban (Xarelto, Janssen Pharmaceuticals) should be approved for the treatment of ACS.
ATLAS ACS 2 – TIMI 51 was a randomized, double blind, placebo-controlled, event-driven study that enrolled 15,526 patients. Study results showed that rivaroxaban-combined doses were superior to placebo at reducing the risk for the primary efficacy endpoint of the composite of CV death, MI or stroke (HR=0.84; 95% CI, 0.74-0.96). However, patients assigned to 2.5-mg rivaroxaban two times per day (1.3%; HR=3.46; 95% CI, 2.08-5.77) or 5-mg rivaroxaban two times per day (1.6%; HR=4.47; 95% CI, 2.71-7.36) had increased rates for non-CABG TIMI major bleeding vs. placebo (0.4%).
Rivaroxaban is already approved in the United States for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery, and to reduce the risk for stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
Although the FDA is not required to follow the recommendations of the advisory committee, it usually does.