Agency requests additional data
Portola Pharmaceuticals has received a complete response letter from the FDA regarding its biologics license application (BLA) for andexanet alfa (AndexXa), a modified human factor Xa molecule. The FDA requested that Portola provide additional information primarily related to manufacturing. The agency also asked for additional data to support the inclusion of edoxaban and enoxaparin in the label.
Andexanet alfa is in development for patients treated with a direct factor Xa inhibitor (apixaban [Eliquis, Bristol-Myers Squibb/Pfizer], rivaroxaban [Xarelto, Janssen], or edoxaban [Savaysa, Daiichi Sankyo]) or an indirect factor Xa inhibitor (enoxaparin [Lovenox, Sanofi-Aventis]) when the reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding. Currently, there is no FDA-approved antidote for factor Xa inhibitors.
Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thereby potentially allowing the restoration of normal hemostatic processes. Andexanet is the first compound being studied as an antidote for factor Xa inhibitors that directly and specifically reverses anti-factor Xa activity––the anticoagulant mechanism of these agents.
The BLA for andexanet alfa was based on data from two phase 3 studies that evaluated the safety and efficacy of andexanet in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban in older healthy volunteers. Results from those studies were published online in the New England Journal of Medicine in November 2015.
The BLA also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study. Andexanet is being evaluated in this global, phase 3b/4 single-arm, open-label, confirmatory study in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.
The FDA had granted andexanet alfa an orphan drug designation.
Annually, 1% to 4% of patients treated with factor Xa inhibitors experience major bleeding, and an additional 1% may require emergency surgery. In 2015, more than 80,000 patients treated with oral factor Xa inhibitors were admitted to hospitals because of bleeding in the U.S.
Source: Portola Pharmaceuticals(link is external); August 18, 2016.
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