Portola Compound Reverses Xarelto

Portola Pharmaceuticals has posted initial results from a Phase II proof-of-concept study of andexanet alfa, its investigational Factor Xa inhibitor antidote, in healthy volunteers who were administered the Factor Xa inhibitor Xarelto (rivaroxaban). Results from the first two dosing cohorts of the study demonstrated that andexanet alfa is able to dose-dependently reverse the anticoagulant effects of Xarelto, with no serious adverse events reported. These data, as well as data from additional cohorts evaluating higher doses of andexanet alfa, will be presented in a poster session on December 9, 2013 at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition.

Andexanet alfa is being developed as a potential first-in-class, universal antidote for patients who experience an uncontrolled bleeding episode or who require emergency surgery while being anticoagulated with a Factor Xa inhibitor. Registration-enabling studies are planned to begin in 2014 as part of a potential Accelerated Approval pathway to address the important unmet need due to a lack of an approved antidote.

This randomized, placebo-controlled, double-blind, cohort dose-escalation Phase II study treated healthy volunteers with an oral dose of Xarelto at 20 mg qd for six days and then randomized them in a 6:3 ratio to andexanet alfa in different dosing cohorts. The first two cohorts received a single IV bolus of andexanet alfa at 210 mg or 420 mg, respectively. Within two minutes following completion of the 210 mg and 420 mg bolus of andexanet alfa, anti-Factor Xa activity decreased dose-dependently by 20% and 53%, respectively. Xarelto-induced inhibition of thrombin generation and prolongation of both prothrombin time and activated clotting time were also rapidly reversed by andexanet alfa in a dose-dependent manner. Interim safety data showed that andexanet alfa was well tolerated, with no thrombotic events, or serious or severe adverse events reported.