Reversal Of Heparin-Induced Anticoagulation By Andexanet Alfa, A Universal Antidote For Factor Xa Inhibitors

Background: Unfractionated heparin is used in the management of venous thromboembolism, stroke prevention in atrial fibrillation as well as in cardiac surgeries (e.g., valve replacement and other procedures requiring cardiopulmonary bypass). Bleeding is the major complication that may result from these therapies. Although protamine sulfate can be used to neutralize heparin, its administration can cause severe hypotensive and anaphylactic reactions. Andexanet alfa (AnXa) is a recombinant modified human fXa under development for the reversal of both direct and antithrombin III (ATIII)-dependent indirect fXa inhibitors. We previously reported nonclinical and Phase 2 clinical data in healthy subjects with enoxaparin, a low molecular weight heparin (LMWH). Here we report new in vitro data demonstrating that AnXa can also effectively reverse anticoagulation of unfractionated heparin.