FDA Committee Recommends Against Expanding Xarelto Indication for ACS

May 23, 2012—The US Food and Drug Administration's (FDA) Cardiovascular and Renal Drugs Advisory Committee has voted against the approval of the oral anticoagulant, Xarelto, (rivaroxaban, Janssen Pharmaceuticals, Inc., Titusville, NJ, a Johnson & Johnson company) to reduce the risk of secondary cardiovascular events in patients with acute coronary syndrome (ACS) in combination with standard antiplatelet therapy.

Xarelto is approved by the FDA for the prophylaxis of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery. The drug is also approved to reduce the risk of both hemorrhagic and thrombotic strokes and other blood clots in patients with atrial fibrillation not caused by a heart valve problem.

According to Janssen, data presented at the FDA advisory committee meeting included results from the phase 3 ATLAS ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With or Without Thienopyridine Therapy in Subjects with Acute Coronary Syndrome) clinical trial. The trial compared rivaroxaban dosed twice daily (BID) in addition to standard therapy (low-dose aspirin with or without a thienopyridine such as clopidogrel) with standard therapy alone in the composite primary efficacy endpoint of cardiovascular-related deaths, heart attacks, or strokes in patients with ACS.



Results from the ATLAS ACS 2 TIMI 51 study showed that rivaroxaban, given in combination with standard antiplatelet therapy, was superior to standard therapy alone in preventing secondary cardiovascular events in patients with ACS. In patients receiving rivaroxaban and standard therapy, rates of TIMI major bleeding events not associated with coronary artery bypass graft surgery were low overall, yet statistically significantly increased compared to those treated with standard therapy plus a placebo. These differences were not associated with an excess risk of fatal bleeding.

The company advised that recommendations from the advisory committee will be considered by the FDA in its review of the supplemental new drug application for rivaroxaban in this indication, but the FDA is not bound to follow them. If approved by the FDA, Janssen Pharmaceuticals will commercialize rivaroxaban for this additional indication in the United States.

Bayer AG (Leverkusen, Germany) is the manufacturer and international marketer of rivaroxaban under the brand name Xarelto. Janssen markets Xarelto in the United States under license from Bayer.