FDA panel recommends approval of rivaroxaban for stroke prevention

September 9, 2011

An FDA advisory panel voted 9-2 (with 1 abstention) to recommend approval for rivaroxaban (Xarelto, Johnson & Johnson and Bayer AG), an oral, once-daily anticoagulant as a treatment to prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

An FDA advisory panel voted 9-2 (with 1 abstention) to recommend approval for rivaroxaban (Xarelto, Johnson & Johnson and Bayer AG), an oral, once-daily anticoagulant, as a treatment to prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Two days earlier, FDA staff released a briefing that was critical of the drug's efficacy and safety. The briefing stated that the ROCKET-AF trial failed to show that rivaroxaban was as effective as warfarin, since warfarin was not “used skillfully” in the trial.

According to Forbes online, the FDA brief noted that the time in the therapeutic range (TTR) for warfarin-treated patients was lower in ROCKET-AF than in similar trials with other drugs. The mean TTR for warfarin in ROCKET-AF was 55%, compared to 63% to 73% in other recent warfarin-controlled studies, according to the reviewers. Thus, although the trial was technically a success because it demonstrated that rivaroxaban was noninferior to warfarin, this finding does “not take into account other factors, such as the quality of anticoagulation in the warfarin arm."

The briefing also raised concerns about the safety of rivaroxaban, noting “an excess of strokes in the rivaroxaban arm during the transition from blinded study drug to open-label warfarin at the end of the study.”

“On the one hand, we have patients who are not suited for warfarin for a variety of reasons, and we need some options,” Carla B. Frye, PharmD, BCPS, told Drug Topics. “On the other hand, we have decades of evidence in support of warfarin, and we need to be cognizant that in most patients it is the best choice, based on those decades of evidence."

Frye added that most clinicians agree that they have a few patients for whom warfarin is not a good choice, “especially those who, for whatever reason, cannot be followed in an anticoagulation clinic.”

Frye is an employee of EPI-Q, Inc., a health economics and outcomes research firm that has received grant support from AstraZeneca.

Rivaroxaban is approved in the United States as a short-term treatment to prevent venous thromboembolism in patients undergoing knee- and hip-replacement surgery. FDA is expected to make a decision on this new indication for stroke prevention by early November 2011.

In other developments, Pfizer and Bristol-Myers Squibb Co. are said to also be developing a new blood-thinning drug, apixaban, and are expected to file for FDA approval of the product as a stroke-prevention treatment in patients with atrial fibrillation by the end of this year.