Positive results with antidote for Factor Xa inhibitor
The first Phase 3 study of andexanet alfa, a potential universal Factor Xa inhibitor antidote met its primary and secondary endpoints. Top-line efficacy data from the first of two ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors – Apixaban) studies demonstrated that an intravenous (IV) bolus of andexanet alfa immediately and significantly reversed the anticoagulation activity of the direct Factor Xa inhibitor apixaban.
In the first ANNEXA-A study, 33 older healthy volunteers were given apixaban 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus or to placebo. Efficacy is being evaluated using biomarker endpoints, including anti-Factor Xa levels as the primary endpoint. Secondary endpoints include levels of plasma unbound (free fraction) of apixaban and thrombin generation. Results showed that andexanet alfa immediately and significantly reversed the anticoagulation activity of apixaban. Andexanet alfa was well tolerated with no serious adverse events reported.
In the second ANNEXA-A study, 32 healthy volunteers will be given apixaban 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus followed by a continuous infusion of 4 mg/min for 120 minutes or to placebo. These data are expected in early 2015.
"Factor Xa inhibitors have demonstrated a safety advantage compared with older anticoagulants, but the number of patients on these newer drugs who are admitted to the hospital with a major bleed is growing due to their widespread adoption. To address this critical need, our goal is to advance andexanet alfa to the market as quickly as possible under the FDA breakthrough therapy designation," said William Lis, chief executive officer of Portola Pharmaceuticals.
"These highly statistically significant Phase 3 ANNEXA-A data demonstrate that andexanet alfa has the potential to be the first agent approved as a universal Factor Xa inhibitor antidote. We anticipate filing a Biologics License Application with the FDA for Accelerated Approval at the end of 2015," said John T. Curnutte, M.D., Ph.D., executive vice president of research and development for Portola. "We expect to report additional data this year and next with other Factor Xa inhibitors, including rivaroxaban, edoxaban, betrixaban and enoxaparin."
Detailed data will be presented during the "Clinical Science: Special Reports" session at the American Heart Association 2014 Scientific Sessions on Monday, November 17, 2014.
Press Release Portola Pharmaceuticals October 1