In this publication of The Medical Letter, the mechanism of action, clinical studies, adverse events, and dosage and cost of andexanet alfa, a reversal agent for the anticoagulant effects of factor Xa inhibitors apixaban, rivaroxaban, betrixaban and edoxaban, are discussed. Andexanet alfa received an accelerated approval from the US Food and Drug Administration (FDA) based on two randomized, placebocontrolled studies (ANNEXA-A and ANNEXA-R) that evaluated change in anti– factor Xa activity following administration of andexanet alfa to healthy volunteers who had received apixaban or rivaroxaban. The interim results from the ongoing ANNEXA-4 trial suggested reduced anti–factor Xa activity by andexanet alfa by 75–91% in patients taking enoxaparin, rivaroxaban or apixaban. Thromboembolic events were observed in 11% of patients and death occurred in 12% of patients within 30 days after administration of andexanet alfa. No data from phase III trials demonstrating efficacy of andexanet alfa have yet been published, and the FDA has requested a randomized, controlled trial comparing andexanet alfa with standard of care in patients taking factor Xa inhibitors who have active bleeding.
Although andexanet alfa effectively reverses the anticoagulant effects of apixaban and rivaroxaban, data are lacking on its efficacy in reversing edoxaban and the indirect factor Xa inhibitor fondaparinux.