BMS, Pfizer, Portola Form Pact for Anticoagulant Antidote
Pfizer and Bristol-Myers Squibb have entered into a collaboration agreement with Portola Pharmaceuticals Inc., a San Francisco-based biopharmaceutical company, to develop and commercialize the investigational agent, andexanet alfa in Japan. Andexanet alfa, which is in Phase III clinical development in the US and Europe, is designed to reverse the anticoagulant activity of Factor Xa inhibitors, including Eliquis (apixaban).
Under the terms of the agreement, Portola will receive an upfront payment of $15 million, potential regulatory milestones of $20 million, and sales-based milestones of $70 million as well as compensation based on andexanet alfa net sales. Bristol-Myers Squibb and Pfizer will co-fund with Portola the development and commercialization of andexanet alfa in Japan. Portola will retain rights to andexanet alfa outside of Japan and remain responsible for the manufacturing supply.
This agreement builds on the companies' existing clinical collaboration to develop andexanet alfa in the US and Europe. In December 2015, Portola announced it had completed the submission of a biologics license application to the US Food and Drug Administration (FDA) for andexanet alfa and was awaiting acceptance for filing. The FDA assigned a PDUFA date of August 17, 2016, under an accelerated approval pathway. Portola has stated that it plans to submit an EU application in 2017.
Andexanet alfa 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.
Separately, Portola has entered into a clinical collaboration agreement with Bayer HealthCare to include its Factor Xa inhibitor rivaroxaban in this clinical development program in Japan. Three oral Factor Xa inhibitors are currently on the market in Japan: Bristol-Myers Squibb and Pfizer's apixaban, Bayer HealthCare's rivaroxaban, and Daiichi Sankyo's edoxaban, but an antidote is not yet approved.
Under the terms of the Bayer clinical collaboration agreement, Portola will receive an upfront payment of $5 million and is eligible to receive an additional milestone payment based on Japanese approval of andexanet alfa as an antidote for rivaroxaban. Bayer will provide technical support as well as fund clinical studies of andexanet alfa with rivaroxaban in Japan. Bayer will receive no commercial rights under this agreement. Portola previously entered into two separate non-exclusive clinical collaboration agreements with Bayer HealthCare and its development partner, Janssen Pharmaceuticals, Inc. to support Phase II and Phase III studies of andexanet alfa and rivaroxaban in the United States and Europe. Portola may receive additional milestone payments under these agreements based on developments in the United States and European Union.