Rivaroxaban Is One Step Closer to Gaining Approval for ACS in Europe After Committee Issues "Positive Opinion"

On March 22, rivaroxaban (XARELTO®) received a "positive opinion" from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) for treatment in patients with acute coronary syndromes (ACS). The agency's new indication recommendation called for a new strength of the drug (2.5 mg). While this recommendation show progress in the drug gaining approval for ACS in Europe, the final decision lies in the hands of the European Commission.

The EMA's recommendation comes just weeks after the U.S. Food and Drug Administration (FDA) rejected rivaroxaban for the second time for ACS in early March. While the ATLAS ACS 2-TIMI 51 found that rivaroxaban "significantly reduced the primary efficacy end point of death from cardiovascular causes, myocardial infarction, or stroke" in patients with ACS, the FDA found the risk of bleeding to be too great to approve the drug for this patient population, prompting the agency to issue a complete response letter.

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The FDA previously rejected rivaroxaban for ACS in June 2012 just after the FDA's Cardiovascular and Renal Drugs Advisory Committee voted against approval following a day-long meeting that focused primarily on the ATLAS ACS 2-TIMI 51 trial, including its design and execution and missing data. The FDA is not required to take the recommendations of the panel, but it often does, as was the case here.

Rivaroxaban is an oral anticoagulant that acts by selective direct inhibition of factor Xa (FXa). The company's Janssen Research & Development unit recently applied for approval of rivaroxaban, to reduce the risk of thrombotic cardiovascular events in patients with ACS [ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), or unstable angina (UA)] in combination with aspirin alone or with aspirin plus clopidogrel or ticlopidine.

In 2012, the FDA approved rivaroxaban for the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and to reduce the risk of recurrence of DVT and PE following initial treatment. In 2011, the drug was approved for the prevention of stroke in nonvalvular atrial fibrillation. The drug was tested and found noninferior vs. warfarin among high-risk patients with atrial fibrillation in the ROCKET AF trial in 2010. Rivaroxaban is also approved for preventing DVT after knee or hip replacement surgery.

According to the FDA, rivaroxaban should be taken one time a day with the evening meal so that it will be completely absorbed. An FDA-required Medication Guide, given to patients and caregivers when rivaroxaban is dispensed, describes the risks and adverse reactions people should be mindful of when using the drug. In addition, a boxed warning also makes it clear that patients using the drug should not discontinue it before talking with their health care professional since discontinuing the drug can increase the risk of stroke.

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Morpholines, Pulmonary Embolism, Thiophenes, Warfarin, Ticlopidine, Europe, Advisory Committees, United States Food and Drug Administration, Venous Thrombosis, Factor Xa, United States

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