The US Food and Drug Administration (FDA) has rejected a bid by Johnson & Johnson and Bayer to expand the uses of their anticoagulant Xarelto.
For the third time, the agency turned down an application for the use of Xarelto (rivaroxaban) to prevent heart attacks, stroke or death in patients with acute coronary syndromes (ACS), an expected result given that an FDA advisory committee voted 10-0 against approval last month.
As well as denying the ACS indication, the FDA also turned down an application from J&J and Bayer seeking approval of Xarelto to reduce the risk of thrombosis in patients who have been fitted with a cardiovascular stent.
J&J said in a statement it was evaluating the Complete Response Letters (CRLs) sent by the FDA informing it of the decisions and that the company will “determine the appropriate next steps.”
Both marketing applications were based on results from the 15,000-patient ATLAS ACS 2 TIMI 51 trial. This study included patients on chronic Xarelto therapy, but J&J and Bayer’s latest filing for ACS specified a defined, 90-day course of treatment based on a re-analysis of the trial data.
The FDA panel indicated last month it was unhappy that no new trial had been undertaken to prospectively test the proposed Xarelto regimen in this setting, and was also concerned about missing follow-up data on around 400 patients that could compromise the statistical rigour of its findings.
Xarelto is already approved in the US to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), as well as to prevent deep vein thrombosis (DVT) following hip- or knee-replacement surgery and for the treatment of DVT and pulmonary embolism.
Bayer persuaded the European Commission (EC) that the drug should be approved in ACS patients with elevated cardiac biomarkers last year, but the failure to win US approval means Xarelto has a gap in its indications compared to rival anticoagulants, such as AstraZeneca’s Brilinta (ticagrelor) and Lilly’s Effient (prasugrel).
That said, Xarelto’s closest competition from the new generation of anticoagulants – Bristol-Myers Squibb and Pfizer’s Eliquis (apixaban) and Boehringer Ingelheim’s Pradaxa (dabigatran) – were also turned down for use in ACS by the FDA, but this has not held back the momentum of either product.
Sales are also buoyant for Xarelto, with J&J reporting turnover of $864m last year, up from $239m in 2012. Bayer will report full-year 2013 figures later this month but recorded sales of around $860m in the first nine months of that year, a more than threefold increase on 2012.