Xarelto to Receive Priority FDA Review for DVT and PE Indications; Company Withdraws sNDA for Stent Thrombosis in ACS

July 9, 2012—Janssen Research & Development, LLC (Janssen R&D, Raritan, NJ) announced that the US Food and Drug Administration (FDA) has assigned a priority review designation to the supplemental New Drug Applications (sNDAs) filed on May 2, 2012, for the oral anticoagulant Xarelto (rivaroxaban), seeking new indications to treat patients with deep vein thrombosis (DVT), pulmonary embolism (PE), and to prevent recurrent DVT and PE.

The FDA grants priority review to medicines that offer major advances in care or provide a treatment where no adequate therapy exists. Under the Prescription Drug User Fee Act, the FDA will aim to complete its review within 6 months from the receipt of the sNDA submission, rather than the standard 10-month review cycle.

According to Janssen R&D, the submissions are supported by data from the global EINSTEIN program, which includes two phase 3 studies evaluating the safety and efficacy of rivaroxaban in the treatment of patients with acute symptomatic DVT or PE and the prevention of recurrent events in these patients. A third phase 3 study evaluated the safety and efficacy of rivaroxaban in the long-term prevention of recurrent DVT and PE. In total, these studies included more than 9,400 patients.

Separately, Janssen R&D announced it is withdrawing the sNDA for the use of Xarelto to reduce the risk of stent thrombosis in patients with acute coronary syndrome (ACS). The company is withdrawing because it is contingent on a separate sNDA for Xarelto to reduce of the risk of secondary cardiovascular events in patients with ACS in combination with standard antiplatelet therapy.

On May 23, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted against the approval of Xarelto for this indication. Janssen R&D received a complete response letter from the FDA on June 21, 2012. The company's reply to the complete response letter is pending. In addition to this sNDA, Janssen R&D has submitted three filings to the FDA that are currently under review.

The company noted that data from the 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) trial support both sNDAs.

As summarized by Janssen R&D, the trial compared rivaroxaban dosed twice daily 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. The results showed that rivaroxaban combined 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, noted the company.

“We remain confident in the overall study results from the ATLAS ACS 2 TIMI 51 trial, including the observed reduction in stent thrombosis that formed the basis for this separate sNDA,” said Paul Burton, MD, PhD, Vice President, Cardiovascular Franchise Medical Leader at Janssen R&D in a press release. “Our top priority is to work with the FDA on our original sNDA for ACS and submit our reply to the complete response letter as soon as possible. We plan to resubmit the sNDA for stent thrombosis at the same time."

Rivaroxaban is being jointly developed by Janssen R&D and Bayer HealthCare (Leverkusen, Germany). In the United States, Janssen Pharmaceuticals, Inc. (Titusville, NJ) holds the marketing rights for Xarelto. Janssen R&D and Janssen Pharmaceuticals are part of the Janssen Pharmaceutical Companies of Johnson & Johnson (New Brunswick, NJ).