A US Food and Drug Administration advisory panel lent its support to Bayer/Johnson & Johnson's anticoagulant Xarelto in a new indication yesterday, despite qualms raised by the FDA reviewers of the application.
The Cardiovascular and Renal Drugs advisory committee voted 9-2 in favour of approving Xarelto (rivaroxaban) to prevent stroke and non-central nervous system embolism in patients with atrial fibrillation, with one extension.
Xarelto, an oral factor Xa inhibitor, was filed for the atrial fibrillation indication on the strength of the ROCKET-AF trial which was published in the New England Journal of Medicine last month. The study showed that Xarelto was equivalent to warfarin in terms of its safety and efficacy.
A majority of panellists voted in favour of approval because on balance they believed that ROCKET-AF was large enough to show that Xarelto was at least as good as warfarin in this hard-to-treat population, with the benefit of being easier to administer to patients.
Earlier, the FDA had said it was concerned that patients had not been treated optimally with warfarin, which could render the comparison between the two drugs unsound. At issue was the time spent in therapeutic range (TTR) for warfarin-treated patients, which at around 58% was lower than for other warfarin studies.
While a subgroup analysis of the study suggested Xarelto was superior to warfarin in stroke prevention in some patients, none of the panellists agreed with this interpretation of the data. On the TTR issue opinion was divided, but on balance the committee supported the view that the low rate could have been because the patients in the study were particularly sick, making warfarin treatment difficult to administer effectively.
One panellist voted against approval, while another said Xarelto's use should be restricted to a third-line setting after other anticoagulant therapies had been tried, reflecting the fact that Boehringer Ingelheim's Pradaxa (dabigatran) is now an alternative to warfarin in this setting. There were no concerns raised about the safety of the new drug.
The FDA does not have to follow the advice of its advisory panel, but generally does so. The agency is now expected to make a final decision by November 5.
If approved, Xarelto will be marketed in the USA by J&J unit Janssen Pharmaceuticals. Bayer has marketing rights for rivaroxaban in all markets outside the USA.