FDA reviewer requests complete response on rivaroxaban

A reviewer at the FDA has requested a complete response from the manufacturer of rivaroxaban, with a discussion and panel recommendation to come at a Thursday meeting of the Cardiovascular and Renal Drugs Advisory Committee.

“The data from the [Johnson & Johnson] Phase 3 ROCKET trial comparing rivaroxaban to warfarin are not adequate to determine whether rivaroxaban is as effective for its proposed indication in comparison to warfarin when the latter is used skillfully,” the FDA stated in the briefing document.

Rivaroxaban (Xarelto, Johnson & Johnson) was tested and found noninferior vs. warfarin (Coumadin, Bristol-Meyers Squibb) among high-risk patients with atrial fibrillation in the ROCKET AF trial in 2010. This double blind, double dummy study enrolled 14,264 patients, of whom 55% had a prior stroke, transient ischemic attack or embolism.

In the original study, researchers found that rivaroxaban was associated with a decreased rate of stroke and non-central nervous system embolism vs. warfarin. Although it was not superior to warfarin, rivaroxaban was determined to be noninferior to warfarin. The FDA said the noninferior result was not enough to warrant approval.

“In order for atrial fibrillation patients to be protected from the risk of thrombotic events, a new drug for this indication should be demonstrated to be as effective as warfarin when it is used skillfully,” the agency stated.

According to the briefing document released by the agency, the noninferior result is not the only cause to withhold approval. There is also insufficient information on rivaroxaban to determine whether it is safe for use. The ROCKET trial showed an excess number of strokes in the rivaroxaban arm, and “proposed instructions for the transition from rivaroxaban to warfarin have not been evaluated or shown safe in terms of bleeding risk or embolic risk.”

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