FDA issues complete response letter for ACS indication for rivaroxaban

June 22, 2012

FDA issued a complete response letter regarding a supplemental New Drug Application for rivaroxaban (Xarelto, Janssen Research & Development) for the reduction of the risk of secondary cardiovascular events in patients with acute coronary syndrome.

FDA issued a complete response letter (CRL) regarding a supplemental New Drug Application (sNDA) for rivaroxaban (Xarelto, Janssen Research & Development) for the reduction of the risk of secondary cardiovascular events in patients with acute coronary syndrome (ACS).

Janssen said in a press release that it is evaluating the CRL and will respond to the agency’s questions.

On May 23, FDA’s Cardiovascular and Renal Drugs Advisory Committee narrowly voted against recommending approval of rivaroxaban in this indication. According to Reuters, the panel said rivaroxaban looked promising, but expressed concern about missing clinical-trial data and bleeding risks.

“We are confident in the robust study results of the ATLAS ACS 2 TIMI 51 trial and the positive benefit-risk profile of rivaroxaban in patients with ACS. We will continue to work with the FDA to fully address their questions as quickly as possible,” said Paul Burton, MD, PhD, vice president, Cardiovascular Franchise Medical Leader at Janssen R&D.

In the United States, rivaroxaban is approved for 3 clinical uses, including to reduce the risk of blood clots in the legs and lungs of people who have just had knee replacement surgery; to reduce this risk in people who have just had hip replacement surgery; and to reduce the risk of both hemorrhagic and thrombotic strokes as well as other blood clots in people with atrial fibrillation not caused by a heart valve problem.

ACS is a complication of coronary heart disease, which is the leading cause of death in the United States, and one of the most prevalent non-communicable diseases in the world. ACS occurs when a blood clot blocks a coronary artery, reducing blood supply to the heart. This disruption of blood flow can cause a heart attack, or unstable angina, a condition signifying that a heart attack may soon occur. Each year, an estimated 1.2 million patients in the United States are discharged from the hospital with a diagnosis of ACS.

Janssen R&D submitted this sNDA December 29, 2011, and received a priority review designation from FDA on February 27, 2012. The sNDA includes results from the pivotal phase 3 ATLAS ACS 2 TIMI 51 (Anti-Xa Therapy to Lower cardiovascular events in Addition to aspirin with/without thienopyridine therapy in Subjects with Acute Cornery Syndrome) clinical trial of rivaroxaban, which were presented at the American Heart Association annual Scientific Sessions in November 2011 and simultaneously published by New England Journal of Medicine.