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news.Portola Pharmaceuticals has entered into a clinical collaboration agreement with Daiichi Sankyo to develop andexanet alfa as an antidote for edoxaban, Daiichi Sankyo’s Factor Xa inhibitor, in Japan.
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Portola is developing andexanet alfa, a U.S. Food and Drug Administration (FDA)-designated Breakthrough Therapy, for patients treated with a direct or indirect Factor Xa inhibitor when reversal of anticoagulation is needed, such as for life-threatening or uncontrolled bleeding or emergency surgery and urgent procedures.
Under the terms of the agreement with Daiichi Sankyo, Portola will receive an upfront payment and is eligible to receive an additional milestone payment based on Japanese Ministry of Health, Labor and Welfare (MHLW) approval of andexanet alfa as an antidote for edoxaban.
Daiichi Sankyo will provide technical support and fund all clinical studies of andexanet alfa with edoxaban in Japan. Daiichi Sankyo will receive no commercial or financial rights under this agreement.
This agreement follows recent agreements with Bristol-Myers Squibb (BMS), Pfizer Inc. and Bayer Healthcare to develop and commercialize andexanet alfa in Japan.
Under those agreements, BMS and Pfizer will be responsible for development, regulatory and commercial activities for andexanet alfa in Japan. Bayer will fund development of andexanet alfa as an antidote for rivaroxaban in Japan. Under this new agreement with Daiichi Sankyo, edoxaban will also be included in the andexanet alfa clinical development program in Japan.
Portola previously entered into eight separate non-exclusive clinical collaboration agreements with Daiichi Sankyo, BMS, Pfizer, Bayer and Janssen to support Phase 2 and Phase 3 studies of andexanet alfa and edoxaban in the United States, Europe and Japan. Portola may receive additional payments under these agreements. Portola retains all rights, including full commercial and financial rights, for andexanet alfa outside of Japan.
About the Need for a Factor Xa Inhibitor Antidote
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 to 4 percent of patients treated with Factor Xa inhibitors may experience major bleeding, and an additional 1 percent may require emergency surgery.
In Japan, three oral Factor Xa inhibitors are currently on the market – Daiichi Sankyo’s edoxaban, BMS and Pfizer’s apixaban, and Bayer HealthCare’s rivaroxaban. Based on data from IMS Health, in the 12 months ending September 2015, sales of these novel oral anticoagulants in Japan exceeded $800 million. There is an unmet need for an antidote for some patients.
About Andexanet Alfa
Andexanet alfa, an investigational drug, is a modified human Factor Xa molecule that acts as a decoy to target and sequester with high specificity 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, thus allowing for the restoration of normal hemostatic processes. Andexanet alfa is the only compound being studied as an antidote for Factor Xa inhibitors that directly and specifically corrects anti-Factor Xa activity – the anticoagulant mechanism of these agents.
Portola’s Biologics License Application (BLA) for andexanet alfa was accepted for filing by the FDA’s Center for Biologics Evaluation and Research (CBER) and assigned a Prescription Drug User Fee Act (PDUFA) date of August 17, 2016.
The BLA was based on data from preclinical, Phase 1 and 2, manufacturing and Phase 3 studies. The Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors) studies 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 those studies were published by 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 Phase 4 ANNEXA-4 study.
Portola is currently evaluating andexanet alfa in this global, 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 to the hospital with an acute major bleed.