Bayer HealthCare's partner, Janssen Research & Development, has submitted its reply to the complete response letter from the FDA for the use of rivaroxaban (Xarelto) 2.5 mg twice daily in combination with standard antiplatelet therapy to reduce the risk of secondary cardiovascular events in patients with acute coronary syndrome (ACS).
The submission includes the information requested by the FDA in its letter to Janssen Research & Development on June 21.
In addition, the supplemental new drug application (sNDA) for the use of rivaroxaban, in combination with standard antiplatelet therapy, to reduce the risk of stent thrombosis in patients with ACS has been resubmitted. Data from the ATLAS ACS 2-TIMI 51 trial support both filings.
In Europe, an application for marketing authorization of rivaroxaban for secondary prevention after an ACS was submitted in December 2011 and is currently under review.
The 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) study was designed to test the efficacy of rivaroxaban compared to placebo in preventing cardiovascular death, MI or stroke in patients after an ACS. Patients were given standard antiplatelet therapy plus rivaroxaban dosed at 2.5 mg or 5 mg BID, or a placebo. Of the 15,526 patients randomized into the study, 93 percent received aspirin plus thienopyridine in addition to rivaroxaban or placebo, and the balance were treated with aspirin plus rivaroxaban or placebo.
On May 23, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted against recommending approval of rivaroxaban in this indication. The bulk of the day's discussion and debate focused in and around the missing data from the ATLAS ACS trial.
However, at the conclusion of the panel meeting, FDA representatives seemed to leave some room open for further discussion on the fate of rivaroxaban in this patient population, and this resubmission of the sNDA solidifies that the company isn't giving up either.
The double blind, randomized, placebo-controlled study was coordinated by the TIMI Study Group and Brigham and Women's Hospital and Harvard Medical School in Boston, and was funded and led by Bayer and Janssen Research & Development, a Johnson & Johnson company.