Portola Pharmaceuticals Inc.announced that the MAA for IndexXa™ (andexanet alfa; trade name in the United States is AndexXa™), a Factor Xa inhibitor antidote, has been submitted to the EMA, completed the validation period, and has been accepted for review. IndexXa is in development for patients treated with a Factor Xa inhibitor when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding and for patients requiring urgent or emergency surgery.
Portola is seeking conditional approval of IndexXa in the EU through the centralized procedure. With the acceptance of the application, the EMA’s Committee for Medicinal Products for Human Use (CHMP) will now begin the centralized review procedure under a standard 210-day review period.
“An estimated 73,000 patients treated with an oral Factor Xa inhibitor will be hospitalized this year due to major bleeding or because they require urgent surgery in the EU5i. These patients are critically ill and could potentially benefit from a Factor Xa inhibitor antidote,” said Bill Lis, chief executive officer of Portola. “As there is currently no approved antidote for Factor Xa inhibitors in the EU, we are working diligently to bring IndexXa to patients. The MAA validation is an important milestone toward achieving that goal.”
Portola’s MAA submission is based on data from two Phase 3 ANNEXA™ studies that evaluated the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. Results of the ANNEXA studies were published by The New England Journal of Medicine. The MAA also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study. Portola is currently evaluating andexanet alfa in this global, Phase 3b/4 single-arm, open-label study in patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin who present with an acute major bleed. The study is enrolling patients in the United States, Canada and the EU.
On August 17, 2016, Portola received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its Biologics License Application (BLA) for AndexXa. The Company plans to meet with the FDA as soon as possible in order to resolve the outstanding questions in the CRL and determine appropriate next steps
