FDA Panel and Staff Split on Approval of Xarelto for Atrial Fibrillation

An advisory panel voted in favor of approving Xarelto to prevent strokes in atrial fibrillation patients days after agency staff recommended against approval.

An FDA advisory panel voted last Thursday to recommend approval of the anticoagulant Xarelto (rivaroxaban) to prevent strokes in atrial fibrillation (AF) patients just two days after agency staffers released an extensive report recommending against approval. The agency, which usually—though not always—follows the recommendations of its advisory panels, is expected to make a decision on whether to approve the oral direct factor Xa inhibitor to treat AF by early November.

Rivaroxaban was approved by the FDA in July to prevent blood clots in patients getting knee and hip replacements. It is one of a number of new oral anticoagulants vying for approval to treat the much larger pool of patients with AF. Since the 1950s, warfarin has been the standard oral anticoagulant, though it has a number of drawbacks including dosing challenges, risk of bleeding, and interactions with numerous foods and medications. Pradaxa (dabigatran) was approved for treating AF last fall, and other candidates in addition to rivaroxaban include Eliquis (apixaban).

In a press release announcing the stamp of approval from the advisory panel, Johnson & Johnson, which manufactures rivaroxaban along with Bayer, cited results of the ROCKET AF trial comparing rivaroxaban with warfarin in 14,264 patients with non-valvular AF who were at risk of stroke and non-CNS systemic embolism. According to the company, in the trial rivaroxaban demonstrated a 21% risk reduction in stroke and non-systemic embolism compared to warfarin with low and comparable bleeding rates.

"We are pleased with the committee's recommendation and look forward to working with the FDA to help make this important therapy available in the US," said Peter M. DiBattiste, head of cardiovascular research for Johnson & Johnson, in the release.

Rivaroxaban’s path to approval may be complicated, however, by the 388-page FDA staff report released last Tuesday. The report recommended against approving rivaroxaban for AF patients on the grounds that the ROCKET trial failed to make clear how safe rivaroxaban is and whether it is as effective as warfarin. “ROCKET does not show convincingly that rivaroxaban is as effective as warfarin when the latter is used skillfully,” said the staff report, according to the Associated Press.

By contrast, the staff report argues that the RE-LY study comparing dabigatran with warfarin clearly demonstrated the latter’s superiority in terms of preventing stroke and blood clots, the AP adds. “It seems advisable to make rivaroxaban a third-line agent, behind both warfarin and dabigatran,” the staff report concludes.

Sources

FDA Advisory Committee Recommends Approval of Oral Anticoagulant Rivaroxaban for the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation [Johnson & Johnson Press Release]

FDA staff recommends against J&J clotting drug [Associated Press]