January 22, 2014 — The U.S. Food and Drug Administration's (FDA) Cardiovascular and Renal Drugs Advisory Committee voted against the approval of the use of oral anticoagulant Xarelto (rivaroxaban) to reduce the risk of thrombotic cardiovascular events in patients with Acute Coronary Syndrome (ACS) in combination with standard antiplatelet therapy. Janssen Research & Development LLC sought approval of rivaroxaban at a proposed dose of 2.5 mg twice daily (BID) for a 90-day treatment duration.
"We appreciate the thoroughness of the committee's review and continue to believe rivaroxaban, in addition to the current standard of care, may help provide patients with ACS additional protection against life-threatening cardiovascular events such as death, heart attack and stroke," said Paul Burton, M.D., Ph.D., vice president of Clinical Development at Janssen. "We will work with the FDA to address questions raised today."
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. Each year, an estimated 1.2 million patients across the nation are discharged from hospitals with a diagnosis of ACS.
The advisory committee's recommendation was based on review of the 15,526-patient 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 Coronary Syndrome) clinical trial of rivaroxaban.
In August 2013, Janssen issued a resubmission to the complete response from the FDA for rivaroxaban 2.5 mg twice daily (BID) to reduce the risk of secondary cardiovascular events in patients with ACS for a 90 day treatment duration. Recommendations from the advisory committee today will be considered by the FDA in its review of the supplemental New Drug Application (sNDA) for rivaroxaban in this indication, but the recommendation of the advisory committee panel is not binding. If approved by the FDA, Janssen Pharmaceuticals Inc. will commercialize rivaroxaban for this additional indication in the United States.
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 Thrombolysis In Myocardial Infarction (TIMI) major bleeding events not associated with coronary artery bypass graft (CABG) surgery were low overall, yet statistically significantly increased versus those treated with standard therapy plus a placebo. Importantly, these differences were not associated with an excess risk of fatal bleeding.
About Xarelto (rivaroxaban)
Xarelto works by blocking the blood clotting Factor Xa. It does not require routine blood monitoring. Xarelto is approved for six indications including:
1. To reduce the risk of strokes and blood clots in patients with atrial fibrillation not caused by a heart valve problem.
2. To treat patients with deep vein thrombosis (DVT).
3. To treat patients with pulmonary embolism (PE).
4. To reduce the risk of recurrence of DVT or PE following an initial six-month treatment for acute venous thromboembolism.
5. To reduce the risk of blood clots in the legs and lungs of patients who have undergone knee replacement surgery.
6. To reduce the risk of blood clots in the legs and lungs of patients who have undergone hip replacement surgery.
Janssen Research & Development LLC, and Bayer HealthCare together are developing rivaroxaban.
For more information: www.xarelto-us.com
February 16, 2024 
