The U.S. Food and Drug Administration (FDA) granted approval to andexanet alfa, also known as coagulation factor Xa (recombinant), inactivated-zhzo, for the reversal of the anticoagulant effects of rivaroxaban and apixaban. This agent is the first FDA-approved antidote for these newer factor Xa inhibitors, and is indicated for use when patients require rapid reversal of anticoagulation due to life-threatening or uncontrolled bleeding.
The FDA’s decision is based on findings from two phase III trials from the ANNEXA program, which evaluated the safety and efficacy of andexanet alfa in healthy volunteers. Rivaroxaban-treated patients experienced a median decrease in anti–factor Xa activity from baseline of 97 percent; anti–factor Xa decreased a median of 92 percent in apixaban-treated patients.
The most common AEs in patients receiving andexanet alfa included urinarytract infections, pneumonia, and infusionrelated reactions.
Arterial and venous thromboembolic events, ischemic events, sudden deaths, or instances where a thrombotic event could not be ruled out were observed within 30 days of andexanet alfa administration in 33 of 185 patients (17.8%) evaluable for safety in the ongoing ANNEXA-4 study. Because of this thromboembolic risk, the FDA labeling advises clinicians to monitor patients for signs and symptoms of these events and to resume anticoagulation as soon as medically appropriate following andexanet treatment.
The approval comes after long delays in the review of andexanet’s biologics license application: In December 2017, the FDA extended the BLA review for the second time, after the drug’s manufacturer, Portola Pharmaceuticals, submitted additional data from the ANNEXA-4 study.
Source: Portola Pharmaceuticals, Inc. press release, May 3, 2018.