Phase III ANNEXA-A study of andexanet alfa antidote for Eliquis (apixaban) achieved endpoints- Portola Pharmaceuticals

Portola Pharmaceuticals, Bristol-Myers Squibb and Pfizer Inc. announced full results from the second part of the Phase III ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors -- Apixaban) study. This registration-enabling study evaluated the safety and efficacy of andexanet alfa, an investigational antidote and FDA-designated breakthrough therapy, administered as an intravenous (IV) bolus followed by a continuous two-hour infusion to sustain the reversal of anticoagulation activity of the Factor Xa inhibitor Eliquis (apixaban) in healthy volunteers aged 50–75 years.

This second part of the study achieved all primary and pre-specified secondary endpoints with high statistical significance. Andexanet alfa produced rapid reversal of the anticoagulant effect of Eliquis, as measured by anti-Factor Xa activity, which was sustained for the duration of the infusion. Andexanet alfa significantly reduced the level of free unbound Eliquis in the plasma and restored thrombin generation to normal. Andexanet alfa was well tolerated, with no serious adverse events, thrombotic events, or antibodies to Factor X or Xa reported. Mild infusion reactions were reported in six subjects: four in the andexanet arm and two in the placebo arm. No subjects discontinued the study due to an adverse event. The full data set was presented in a Late-Breaking Clinical Trial oral session at the International Society on Thrombosis and Haemostasis (ISTH) 2015 Congress in Toronto.