In animal models, andexanet alfa reduced anti-FXa activity and bleeding associated with edoxaban, rivaroxaban, enoxaparin, and fondaparinux, and helped restore hemostasis. 5,6 Andexanet alfa is a recombinant human FXa that lacks the catalytic activity of native FXa but retains high-affinity binding to FXa inhibitors. These studies were registered with (#NCT03578146 and #NCT03551743).Īndexanet alfa (Andexxa coagulation factor Xa, inactivated-zhzo) has been approved in the United States, and granted a conditional marketing authorization by the European Medicines Agency’s human medicines committee, for patients treated with rivaroxaban and apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. Andexanet alfa has been approved in the United States and Europe for reversal of anticoagulation in patients treated with rivaroxaban or apixaban who experience life-threatening or uncontrolled bleeding. Andexanet alfa was well tolerated, and there were no serious adverse events or thrombotic events. Sustained normalization of thrombin generation for ≈2 hours and sustained decrease in unbound anticoagulant (maximum ≈80%) for up to ≈4 hours following completion of andexanet alfa administration, compared with placebo, were observed when andexanet was administered as a bolus or as a bolus followed by continuous infusion. The stoichiometric ratios of andexanet alfa:total anticoagulant at maximum reversal of anti-FXa activity ranged from 1:1 to 1.3:1 for rivaroxaban and 1.41:1 to 2.58:1 for edoxaban. 05), respectively, compared with placebo. Within 2 minutes after bolus, anti-FXa activity decreased significantly, with maximum decreases of ≈93% ( P <.
Andexanet alfa rapidly and effectively reversed anticoagulation with both rivaroxaban and edoxaban. In two phase 2, randomized, double-blind, placebo-controlled, single-center studies, different regimens of andexanet alfa were administered to healthy volunteers after therapeutic anticoagulation with rivaroxaban or edoxaban, and multiple anticoagulation reversal and safety end points were evaluated.
Andexanet alfa is a recombinant modified human FXa lacking enzymatic activity, developed for reversal of FXa inhibitor–induced anticoagulation. As with any anticoagulant, factor Xa (FXa) inhibitors are associated with a risk of major bleeding.