Bayer and Johnson & Johnson suffered a setback ahead of an advisory committee meeting on the use of their Xarelto blood thinner to prevent stroke in atrial fibrillation, after the US Food and Drug Administration said it would not recommend approval.

Documents released by the FDA ahead of the Cardiovascular and Renal Drugs advisory committee meeting on September 8 suggest that Xarelto (rivaroxaban) should not be approved in this indication because of concerns about the dosing of warfarin in the pivotal trial filed in support of the marketing application.

The results of the ROCKET AF study - which were published in the New England Journal of Medicine last month - showed that Xarelto was equivalent to warfarin in terms of its safety and efficacy. However, an editorial in the same edition of the NEJM raised questions about the dosing of warfarin in the study, suggesting it may have been suboptimal.

The FDA reviewers appear to concur with that view, saying they are concerned about the time spent in therapeutic range for the warfarin group, which at around 58% was lower than for other warfarin studies. They also are concerned about an excess of stroke observed when patients on Xarelto were switched to warfarin at the end of the study, although overall they have no other concerns about the safety of the drug.

Of course, the FDA advisory panel may consider that the benefits of Xarelto outweigh those concerns and recommend approval. The new drug is easier to administer and does not require the intensive dose titration and monitoring that is required for warfarin. There have also been suggestions that the patients enrolled into the ROCKET AF study were particularly ill, which could have made warfarin treatment harder to manage.

Xarelto was approved in the USA in July for the prevention of deep vein thrombosis which may lead to a pulmonary embolism in people undergoing knee or hip replacement surgery, and has also been filed for this indication in Europe.

It was the second non-warfarin oral blood thinner to reach the market after Boehringer Ingelheim's Pradaxa (dabigatran), which debuted in 2008 and was approved for stroke prevention in AF patients last year.