FDA approvals

FDA denies new indication for Xarelto

Janssen Research and Development announced today that the FDA issued complete response letters regarding supplemental new drug applications for the use of Xarelto to reduce the risk for secondary CV events in patients with ACS and to reduce the risk for stent thrombosis in the same patients, in combination with standard antiplatelet therapy, according to a press release.

Rivaroxaban (Xarelto) is currently approved for the reduction of stroke and systemic embolism risk in patients with nonvalvular atrial fibrillation, as well as for the treatment and prevention of recurrent venous thromboembolism.

“We remain committed to providing patients who have suffered from ACS with additional protection against stent thrombosis and secondary life-threatening CV events,” Paul Burton, MD, PhD, vice president of clinical development for Janssen Research and Development, stated in the release. “We are evaluating the contents of the letters and will determine the appropriate next steps.”

Both supplemental new drug applications were based on results from the pivotal, phase 3 ATLAS ACS 2-TIMI 51 trial of 15,526 patients. In this trial, rivaroxaban recipients had reduced risk for CV death, MI or stroke compared with placebo recipients (HR=0.84; 95% CI, 0.74-0.96), but those assigned the 2.5-mg (1.3%; HR=3.46; 95% CI, 2.08-5.77) or 5-mg twice-daily dose (1.6%; HR=4.47; 95% CI, 2.71-7.36) had increased rates of non-CABG TIMI major bleeding.

In January, an FDA advisory committee 10-0, with one abstention, against recommending approval for Xarelto for these indications. Reasons for the vote included concerns about available data from only one study, a P value above .01 for the primary efficacy endpoint, and the loss of a large number of patients to follow-up. This was the second time the advisory committee voted against approval for the drug.

In response to a separate supplemental new drug application submitted by Janssen in January, the FDA also lifted the requirement for a REMS program for Xarelto. The REMS was initiated in November 2011 and included a communication plan and a timetable for submission of REMS assessments. According to the approval notification from the FDA, the communication plan has been successfully completed, and the REMS is no longer necessary to determine whether the benefits of Xarelto outweigh the potential risks.

Janssen Research and Development announced today that the FDA issued complete response letters regarding supplemental new drug applications for the use of Xarelto to reduce the risk for secondary CV events in patients with ACS and to reduce the risk for stent thrombosis in the same patients, in combination with standard antiplatelet therapy, according to a press release.

Rivaroxaban (Xarelto) is currently approved for the reduction of stroke and systemic embolism risk in patients with nonvalvular atrial fibrillation, as well as for the treatment and prevention of recurrent venous thromboembolism.

“We remain committed to providing patients who have suffered from ACS with additional protection against stent thrombosis and secondary life-threatening CV events,” Paul Burton, MD, PhD, vice president of clinical development for Janssen Research and Development, stated in the release. “We are evaluating the contents of the letters and will determine the appropriate next steps.”

Both supplemental new drug applications were based on results from the pivotal, phase 3 ATLAS ACS 2-TIMI 51 trial of 15,526 patients. In this trial, rivaroxaban recipients had reduced risk for CV death, MI or stroke compared with placebo recipients (HR=0.84; 95% CI, 0.74-0.96), but those assigned the 2.5-mg (1.3%; HR=3.46; 95% CI, 2.08-5.77) or 5-mg twice-daily dose (1.6%; HR=4.47; 95% CI, 2.71-7.36) had increased rates of non-CABG TIMI major bleeding.

In January, an FDA advisory committee 10-0, with one abstention, against recommending approval for Xarelto for these indications. Reasons for the vote included concerns about available data from only one study, a P value above .01 for the primary efficacy endpoint, and the loss of a large number of patients to follow-up. This was the second time the advisory committee voted against approval for the drug.

In response to a separate supplemental new drug application submitted by Janssen in January, the FDA also lifted the requirement for a REMS program for Xarelto. The REMS was initiated in November 2011 and included a communication plan and a timetable for submission of REMS assessments. According to the approval notification from the FDA, the communication plan has been successfully completed, and the REMS is no longer necessary to determine whether the benefits of Xarelto outweigh the potential risks.

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