Portola, Bristol-Myers Squibb, Pfizer Report Phase 3 Trial Results Of Andexanet Alfa

Portola’s andexanet alfa nearly completely reversed the anticoagulant effect of Eliquis (apixaban) in the Phase 3 ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors – Apixaban) studies. Portola announced the results in a press release with its co-development partners Bristol-Myers Squibb (BMS) and Pfizer. Andexanet alfa is an anticoagulant antidote for people who experience a major bleed or who are undergoing emergency surgery. Portola believes strongly in its investigational agent and has contracted with CMC Biologics and Lonza for manufacturing if the agent is approved in the U.S.

Andexanet Alfa

Andexanet alfa is a FDA designated Breakthrough Therapy. The agent binds Factor Xa inhibitors, thereby binding and inhibiting native Factor Xa and restoring the normal hemostatic processes. Andexanet alfa is flexible, acting in the short-term with IV bolus administration, or in the long-term with extended infusion. Portola is preparing a Biological License Application (BLA) for Accelerated Approval.

ANNEXA-A Trial

In the ANNEXA-A trial, andexanet alfa showed a 94 percent complete reversal rate, effectively and rapidly reversing the anticoagulant effect of Eliquis in healthy volunteers ages 50-75. Investigators intend to present the complete results at the American Heart Association (AHA) 2014 Scientific Sessions in Chicago, IL.

In the trial, 24 patients received andexanet alfa and 9 received a placebo. By measuring anti-Factor Xa activity, scientists found that Eliquis anticoagulant activity was reversed within two to five minutes. The reversal was corroborated by the existence of free, unbound Eliquis in the plasma. Thrombin generation returned to baseline levels as well. No serious adverse events were reported although three subjects reported mild infusion reactions.

John T. Curnutte, M.D., Ph.D., EVP of research and development for Portola, said, “The statistically significant reversal of the anticoagulant effect of Eliquis demonstrated in all subjects receiving andexanet alfa reinforces our commitment to bring this antidote to market as quickly as possible under an Accelerated Approval pathway.”

BMS’ Stake

BMS head of specialty development, Douglas Manion, M.D., explained his company’s stake in andexanet alfa, stating the BMS’ Eliquis has no antidote. He said, “Eliquis has proven to be an important treatment option for patients at risk for blood clots due to nonvalvular atrial fibrillation and venous thromboembolism. Currently, there is no antidote to Eliquis. Andexanet alfa has the potential to be an effective option for patients who may require reversal of the anticoagulation effects of Eliquis.”