Portala Pharma completes BLA submission to FDA for andexanet alfa to reverse the anticoagulant activity of both direct and indirect Factor Xa inhibitors

Portola Pharmaceuticals announced completion of the submission of a Biologics License Application (BLA) to the FDA for its investigational agent andexanet alfa, an FDA-designated breakthrough therapy specifically designed to reverse the anticoagulant activity of both direct and indirect Factor Xa inhibitors. Portola is developing andexanet alfa as a universal reversal agent for patients anticoagulated with an oral or injectable Factor Xa inhibitor who experience a serious uncontrolled bleeding event or who require urgent or emergency surgery.

The BLA submission includes data from Portola’s Phase III ANNEXA (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors) studies, which evaluated the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban, respectively, in healthy volunteers. Results of those studies were published online by The New England Journal of Medicine in November 2015. In addition, data from a small number of patients from ANNEXA-4 will serve as the clinical basis for the BLA.

Portola is currently evaluating andexanet alfa in this global Phase 4 single-arm, open-label confirmatory study in patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin (a low molecular weight heparin and indirect Factor Xa inhibitor) who present with an acute major bleed.

Comment: Commensurate with the increase in use of Factor Xa inhibitors, the number of hospital admissions due to bleeding associated with these agents continues to grow. Annually, 1–4% of patients treated with Factor Xa inhibitors may experience major bleeding, and an additional 1% may require emergency surgery. In the United States alone, during the 12 months ended April 2015, there were over 50,000 rivaroxaban or apixaban treated patients admitted to the hospital due to bleeding. This number does not account for patients taking the injectable Factor Xa inhibitor enoxaparin or those on a Factor Xa inhibitor undergoing emergency surgery. In the United States, more than 100,000 patients annually may benefit from a reversal agent. Currently, there is no FDA-approved reversal agent for Factor Xa inhibitors for these patients.