Portola's Factor Xa inhibitor antidote andexanet alfa meets main goal of Phase III study

Portola Pharmaceuticals reported top-line efficacy results Wednesday from a Phase III study demonstrating that its experimental drug andexanet alfa "immediately and significantly" reversed the anticoagulation activity of Pfizer and Bristol-Myers Squibb's Eliquis (apixaban). John Curnutte, executive vice president of R&D at Portola, said the results suggest "andexanet alfa has the potential to be the first agent approved as a universal Factor Xa inhibitor antidote," adding that the company anticipates filing an application with the FDA for accelerated approval at the end of 2015.

In the ANNEXA-A trial, the first of two ANNEXA studies evaluating andexanet alfa in reversing Eliquis-induced anticoagulation, 33 older healthy volunteers were given Eliquis twice daily for four days and then randomised to receive either an intravenous bolus of andexanet alfa or placebo. Portola noted that efficacy is being evaluated using biomarker endpoints, including anti-Factor Xa levels as the main goal. The company indicated that the study met its primary and secondary endpoints, which include levels of plasma unbound of Eliquis and thrombin generation, with "high statistical significance." Portola added that andexanet alfa was well tolerated with no serious adverse events reported, while detailed results from the trial will be presented at the American Heart Association annual meeting in November.

The second ANNEXA-A study involves 32 healthy volunteers who will be administered Eliquis twice daily for four days and then randomly assigned andexanet alfa administered as an intravenous bolus followed by a continuous infusion of the therapy for 120 minutes or placebo. Results from this trial are expected early next year.

Meanwhile, Portola said the planned ANNEXA-E study of andexanet alfa with Daiichi Sankyo's direct Factor Xa inhibitor Lixiana (edoxaban) will be initiated in 2015. Curnutte added "we expect to report additional data this year and next with other Factor Xa inhibitors," including Johnson & Johnson and Bayer's Xarelto (rivaroxaban), Sanofi's Lovenox (enoxaparin), and Portola's own anticoagulant betrixaban. The company noted that betrixaban is in late-stage testing for hospital-to-home prophylaxis of venous thromboembolism in acute medically ill patients.

Portola has entered into clinical collaboration agreements to test andexanet alfa with several direct Factor Xa inhibitors, including Eliquis and Xarelto, but still retains all commercial rights to the drug, which was granted breakthrough therapy status by the FDA last November.

For further analysis, see ViewPoints: Portola leverages support from future competitors into successful data for Factor Xa antidote.

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