SILVER SPRING, Md. -- The FDA has rejected an application for a new indication allowing rivaroxaban (Xarelto) to be used to reduce the risk of stent thrombosis in patients with acute coronary syndrome (ACS).
Manufacturer Janssen Pharmaceuticals announced early Friday that it had received a complete response letter from the FDA rejecting the indication. The contents of complete response letters are not made public, and Janssen did not indicate what concerns the FDA expressed in its decision.
However, the New Jersey drugmaker did say its application to expand the labeling of the blockbuster anticoagulant was based on data from a highly controversial trial -- .
That trial also supports a supplemental new drug application (sNDA) -- which the FDA has now twice rejected -- for rivaroxaban to reduce the risk of strokes and heart attacks in ACS patients. The second complete response letter came in early March.
An FDA advisory panel in May 2012 expressed concern about missing data in the ATLAS ACS 2 TIMI 51 trial, including data on more than 2,400 patients who dropped out of the trial early. Janssen in September 2012 submitted data on patients who had withdrawn from the trial.
Researchers later reported that although there had been some concern about bleeding, out of the more than 1,000 patients who withdrew that they were able to obtain data on, only one patient in the rivaroxaban arm had a bleeding event within 30 days before withdrawal compared with none in the placebo arm.
The overall results of the trial were positive. A 2.5 mg twice-daily dose of rivaroxaban cut the risk of dying from cardiovascular causes by 34%. There was no increase in fatal bleeding.
"We remain confident in the results of the ATLAS ACS 2 TIMI 51 trial and are in ongoing discussions with the FDA regarding this sNDA," Christopher Nessel, MD, vice president of the cardiovascular unit of Janssen, .
The drug is already approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing hip or knee replacement surgery, and for treatment of DVT or PE and reduction in the risk of recurrence of DVT or PE.
Rivaroxaban is the most prescribed novel oral anticoagulant in the U.S., Janssen said, with more than 2 million prescriptions written to date.
The drug was developed in a partnership between Janssen, which is a subsidiary of Johnson & Johnson, and German drugmaker Bayer.
Dabigatran (Pradaxa) was the first novel oral anticoagulant approved in the U.S., and rivaroxaban was approved in late 2011 for the same indication of preventing stroke in patients with nonvalvular atrial fibrillation.