Portola's andexanet alfa achieves all primary, secondary goals of Phase III study

Portola Pharmaceuticals on Monday announced that andexanet alfa, an experimental antidote to Pfizer and Bristol-Myers Squibb's anticoagulant Eliquis (apixaban), met the primary and secondary endpoints of the second part of the Phase III ANNEXA-A trial. In the study, andexanet alfa rapidly reversed the anticoagulating effects of Eliquis, as indicated by anti-Factor Xa activity, and maintained its effects throughout the duration of the infusion. John T. Curnutte, executive vice president of R&D at Portola, commented that the study data, which were also presented at the International Society on Thrombosis and Haemostasis (ISTH) annual congress "demonstrate that andexanet alfa can rapidly reverse anticoagulant activity for a short or sustained period of time and that anticoagulant activity can be reinitiated following discontinuation of the infusion."

In the study, 31 healthy volunteers aged 50 to 75 were treated with Eliquis twice daily for four days and then randomised to receive andexanet alfa, administered as a bolus followed by continues infusion for 120 minutes, or placebo. The primary endpoint of the study was efficacy evaluated using anti-Factor Xa levels, while secondary endpoints included plasma levels of free unbound Eliquis and endogenous thrombin potential.

Results from the study illustrated that the anticoagulant effects of Eliquis were reversed by 93.5 percent after the bolus infusion of andexanet alfa and by 92.7 percent after the two-hour continuous infusion. Meanwhile, andexanet alfa was found to reverse the effects of Eliquis by at least 80 percent in all 23 subjects who received the therapy and demonstrated a substantial reduction in the levels of free unbound Eliquis. Andexanet alfa also restored thrombin generation to the normal range in all participants who received the therapy. Protola further noted that Andexanet alfa administration was not associated with any serious adverse events, thrombotic events or the production of antibodies to Factor X or Factor Xa.

In October last year, Portola announced topline data from the first part of the ANNEXA-A trial showing that andexanet alfa rapidly and significantly reversed the effects of Eliquis. In addition, the company later disclosed findings from the ANNEXA-R trial demonstrating that the drug reversed the effect of Bayer and Johnson & Johnson's anticoagulant Xarelto (rivaroxaban). The drugmaker indicated that it plans to submit data from both studies, as well as the initial results of a Phase IV study, to the FDA as part of its application for approval of andexanet alfa, which has been granted orphan drug and breakthrough therapy status by the agency.

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