Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban

Abstract

New target-specific oral anticoagulants are limited by the lack of a proven reversal agent. PER977 (Perosphere) is a small, synthetic, water-soluble, cationic molecule that is designed to bind specifically to unfractionated heparin and low-molecular-weight heparin through noncovalent hydrogen bonding and charge–charge interactions (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).^1,2 PER977 binds in a similar way to the new oral factor Xa inhibitors, edoxaban, rivaroxaban and apixaban, and to the oral thrombin inhibitor, dabigatran. In thromboelastographic studies and rat-tail–transection bleeding assays, PER977 has been shown to reverse anticoagulation with each of the new oral agents.^1,2 In nonclinical studies, PER977 did not bind to plasma proteins, including albumin, and showed no binding when tested against several common cardiovascular, antiepileptic, and anesthetic drugs. In this study, we assessed the safety, side-effect profile, and effect on anticoagulation reversal of PER977 when administered alone and after a 60-mg dose of the factor Xa inhibitor edoxaban.^3,4