Credit: Mass. General Hospital
A US Food and Drug Administration (FDA) advisory committee has voted against expanding the indication for the anticoagulant rivaroxaban (Xarelto).
The drug’s developers are seeking approval for rivaroxaban to be used in combination with standard antiplatelet therapy to reduce the risk of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). The proposed dose is 2.5 mg twice daily for 90 days.
But the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted—nearly unanimously (with 1 abstention)—against this approval.
And the FDA will take this recommendation into account when deciding whether or not to expand rivaroxaban’s indication. This will be the FDA’s third time reviewing the drug for the aforementioned indication.
Rivaroxaban is currently FDA-approved to reduce the risk of stroke and thrombosis in patients with non-valvular atrial fibrillation, treat patients with venous thromboembolism (VTE), reduce the risk of recurrent VTE, and reduce the risk of VTE in patients who have undergone knee replacement surgery or hip replacement surgery.
Headed for a third rejection?
The advisory committee’s recommendation was based on a review of data from the phase 3 ATLAS ACS 2 TIMI 51 trial, which were published in NEJM in January 2012.
The study showed that rivaroxaban, given in combination with standard antiplatelet therapy, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in ACS patients. But it also increased the risk of major bleeding and intracranial hemorrhage.
Based on these results, rivaroxaban’s developers—Janssen Research & Development, LLC, and Bayer HealthCare—filed for FDA approval of rivaroxaban to treat patients with ACS.
In June 2012, the FDA rejected the application, a month after an advisory committee voted against the approval. The committee had expressed concerns about the risks of bleeding associated with rivaroxaban, as well as reservations about missing data from the ATLAS ACS 2 TIMI 51 trial.
Though Janssen and Bayer went on to submit the missing data, the FDA rejected the drug again in March 2013. However, the FDA suggested the companies apply for approval using rivaroxaban for a limited time after ACS development, as the drug might be safer and more effective when given this way.
So the companies submitted an application for rivaroxaban given within the first 90 days of ACS diagnosis.
The advisory committee voted against this use of the drug, however, saying it seems the benefits of this treatment still do not outweigh the risks for this patient population.
A representative from Janssen said the company still believes rivaroxaban can be useful for patients with ACS, and Janssen and Bayer will work with the FDA to address the issues the committee raised.
For more details and data on rivaroxaban, see the briefing information compiled for the advisory committee’s meeting.
