FDA Advisory Committee recommends against approval of the use of oral anticoagulant XARELTO® to reduce the risk of thrombotic cardiovascular events in patients with Acute Coronary Syndrome

Janssen Research & Development, LLC (Janssen) announced today the U.S. Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee has voted against the approval of the use of XARELTO® (rivaroxaban), an oral anticoagulant, to reduce the risk of thrombotic cardiovascular events in patients with Acute Coronary Syndrome (ACS) in combination with standard antiplatelet therapy. Janssen is seeking 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, Clinical Development, Janssen Research & Development. “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 U.S. 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 U.S. are discharged from the hospital 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, rivaroxaban will be commercialized for this additional indication in the U.S. by Janssen Pharmaceuticals, Inc.

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. XARELTO® does not require routine blood monitoring. XARELTO® has the broadest indication profile of any novel oral anticoagulant and is approved for six indications that include:

1. To reduce the risk of strokes and blood clots in patients with atrial fibrillation not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO® and warfarin compare in reducing the risk of stroke.
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 just had knee replacement surgery.
6. To reduce the risk of blood clots in the legs and lungs of patients who have just had hip replacement surgery.

The extensive program of clinical trials evaluating rivaroxaban makes the compound the most studied oral Factor Xa inhibitor in the world today. By the time of its completion in 2018, approximately 100,000 patients will have participated in the rivaroxaban clinical development program.