The Food and Drug Administration has decided not to approve rivaroxaban for reducing the risk of stent thrombosis in patients with acute coronary syndrome, according to the manufacturer of the anticoagulant.
In a statement issued on June 28, Janssen Research & Development announced that the FDA has issued a complete response letter regarding the company’s application to approve rivaroxaban for this indication. Janssen markets rivaroxaban, an oral factor Xa inhibitor, as Xarelto.
The FDA does not announce when they send a company a complete response letter, issued for a drug when there are outstanding issues that need to be resolved before approval, but manufacturers can make these announcements.
The company filed for approval of this indication based on the results of the ATLAS ACS 2 TIMI 51 (the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome) study, of 15,526 patients with recent ACS. In the study, rivaroxaban reduced the risk of cardiovascular death, MI, or stroke in patients with ACS, with an increase in major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. The study was published in January 2012 (N. Engl. J. Med. 2012;366:9-19).
In the Janssen statement, Dr. Christopher C. Nessel, vice president and medical leader of the cardiovascular franchise at Janssen, said, "We remain confident in the results of the ATLAS ACS 2 TIMI 51 trial and are in ongoing discussions with the FDA regarding" the supplemental new drug application. The Janssen statement did not elaborate on the reasons why the FDA did not approve this indication.
The company used data from the same study to file for approval of rivaroxaban for another indication – to reduce the risk of cardiovascular events in patients with ACS – but has received two complete response letters from the FDA for this indication, most recently in March 2013. Missing data and safety concerns were cited as concerns by FDA panelists recommending against the approval of this indication at an FDA advisory panel meeting in May 2012, but the company did not specify whether this was the reason for the two complete response letters for the ACS indication.
Since it was approved in 2011 for the prophylaxis of deep vein thrombosis in patients undergoing knee or hip replacement surgery and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, rivaroxaban has been approved by the FDA for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE); and for the reduction in the risk of recurrence of DVT and of PE.
It was recently approved in the European Union for in combination with antiplatelet therapy to help prevent atherothrombotic events after acute coronary syndrome.