Portola:Andexanet Alfa Dose-dependently Reversed Xarelto's Anticoagulant Effects

(RTTNews) - Portola Pharmaceuticals, Inc. (PTLA) announced initial results from a Phase 2 proof-of-concept study of andexanet alfa, its investigational Factor Xa inhibitor antidote, in healthy volunteers who were administered the Factor Xa inhibitor Xarelto or 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. No serious adverse events were 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 at the 55th American Society of Hematology Annual Meeting and Exposition being held in New Orleans from December 7-10.

Andexanet alfa is being developed as a potential first-in-class, universal antidote for patients who experience uncontrolled bleeding episode or who require emergency surgery while being anticoagulated with a Factor Xa inhibitor.

The randomized, placebo-controlled, double-blind, cohort dose-escalation Phase 2 proof-of-concept study treated healthy volunteers with an oral dose of Xarelto at 20 mg qd for 6 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 percent and 53 percent, respectively.

Xarelto-induced inhibition of thrombin generation and prolongation of prothrombin time and activated clotting time were also rapidly reversed by andexanet alfa in a dose-dependent manner.

Registration-enabling studies are planned to begin in 2014 as part of a potential accelerated approval pathway to address the unmet need due to a lack of an approved antidote.