Janssen gets 2nd rejection for Xarelto in ACS
This article was originally published in Scrip
For the second time, the US FDA has rejected Janssen Research & Development's supplemental new drug application for Xarelto (rivaroxaban) as a therapy to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS).
The company, a subsidiary of Johnson & Johnson, got the boot the first time last June after the FDA's Cardiovascular and Renal Drugs Advisory Committee a month earlier voted 6-4, with one abstention, against approval for Xarelto in ACS, a term which includes the conditions of unstable angina, ST-elevation myocardial infarction (STEMI) and non-STEMI (scripintelligence.com, 25 June 2012, 24 May 2012).
The advisory committee raised concerns about missing data – or "missingness" – and the increased risk of bleeding events. Indeed, just over 2,400, or 15.5%, of patients dropped out of Janssen's study prematurely, including 1,294, or about 8%, who withdrew their consent. In addition, over 1,000 patients at the end of the trial had an unknown vital status, with incomplete follow-up.
But this past September, Janssen submitted data to the FDA related to patients who had withdrawn from the ATLAS ACS 2 TIMI 51 trial.
The company said it was able to confirm the "vital" status information for 843, or 63%, of the 1,338 trial participants who previously had unknown vital status.
The mortality benefit observed during the treatment phase of the study was maintained. These new events were distributed equally between the three treatment groups – 2.5mg, 5mg and placebo – of the 806 patients who were alive and the 37 who had died.
After those efforts, follow-up data was not available on only 2.4% of patients, the firm said.
Dr Christopher Nessel, vice president at Janssen, said the company remained confident in the "robustness" and results of its ATLAS ACS 2 TIMI 51 trial.
Xarelto, an oral anticoagulant that acts by selective and direct inhibition of factor Xa, is approved in the US as a treatment for vein thrombosis and pulmonary embolism in patients undergoing elective total hip or knee replacement surgery, and as a therapy to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (scripintelligence.com, 4 July 2011).
Janssen, which is partnered with Bayer HealthCare on Xarelto, won a second approval on 4 November 2011 for the drug as a therapy to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. That approval came after an earlier CRDAC backed the drug's use in that indication in a 9-2 vote at a September 2011 meeting (scripintelligence.com, 9 September 2011, 6 September 2011).
The blood-thinning agent also won the FDA's nod this past November as a therapy to treat deep vein thrombosis (DVT) or pulmonary embolism (PE) and to reduce the risk of recurrent DVT and PE following initial treatment (scripintelligence.com, 6 November 2012).
Janssen said it is evaluating the latest complete response letter for Xarelto in the ACS indication from the FDA and would respond to the agency's questions.