Portola Pharmaceuticals, Bristol-Myers Squibb Company, and Pfizer announced results from the Phase 3 ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors – Apixaban) study with andexanet alfa as a reversal agent for Eliquis (apixaban).
ANNEXA-A is a randomized, double-blind, placebo-controlled study, which evaluated the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in older healthy volunteers ages 50–75 years. Efficacy was evaluated using biomarker endpoints, with anti-Factor Xa levels as the primary endpoint. In ANNEXA-A Part 1, 33 healthy volunteers were given apixaban 5mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400mg IV bolus (n=24) or to placebo (n=9). In the second part of the study, 31 healthy volunteers were given apixaban 5mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400mg IV bolus followed by a continuous infusion of 4mg/min for 120 minutes (n=23) or to placebo (n=8).
Results demonstrated that after administrating a bolus of andexanet alfa, the anticoagulant activity of apixaban, was reversed by 93.5% (P<0.0001). Following completion of the two-hour continuous infusion of andexanet alfa, the anticoagulant activity of apixaban remained significantly reversed, by 92.7% (P<0.0001). These two endpoints demonstrate that andexanet alfa infusion was able to keep anti-Factor Xa levels flat from the end of the bolus (93.5%) to the end of the two-hour infusion (92.7%).
Portola plans to submit data from the ANNEXA-A (apixaban) and ANNEXA-R (rivaroxaban) studies, and initial data from a Phase 4 study, as part of its Biologics License Application (BLA) to the FDA by the end of 2015.