Portola Pharmaceuticals has announced that it has licensed the lead development and commercial rights to its investigational agent andexanet alfa in Japan to Bristol-Myers Squibb and Pfizer, to be developed as an antidote for apixaban and other Factor Xa inhibitors. Separately, Portola has entered into a clinical collaboration agreement with Bayer HealthCare to include its Factor Xa inhibitor rivaroxaban in this clinical development programme 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. A universal antidote for Factor Xa inhibitors is needed for certain patients in Japan, as the clinical use of these novel oral anticoagulants is growing.
“These agreements allow Portola to expand the development and commercialisation of andexanet alfa into Japan, which is a new country for us, and the third largest market for Factor Xa inhibitors after the USA and EU five countries,” says William Lis, chief executive officer of Portola. “Bristol-Myers Squibb, Pfizer and Bayer all have extensive infrastructure and experience in Japan. With Bristol-Myers Squibb and Pfizer leading development and commercialisation activities, and Bayer providing support, the path forward for andexanet alfa as a Factor Xa inhibitor antidote in Japan will be accelerated.”
Portola is developing andexanet alfa, a US 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. Portola retains full, worldwide commercial rights to andexanet alfa outside of Japan.
Under the terms of the agreement with Bristol-Myers Squibb and Pfizer, Portola will receive an upfront payment of US$15 million and is eligible to receive potential regulatory and sales-based milestone payments totalling US$90 million, as well as double-digit royalties based on andexanet alfa net sales in Japan. Bristol-Myers Squibb and Pfizer will be responsible for all development and regulatory activities for andexanet alfa in Japan and for commercialising the drug in Japan, assuming it receives regulatory approval from the Japanese Ministry of Health, Labour and Welfare.
Portola has previously entered into two separate non-exclusive clinical collaboration agreements with Bristol-Myers Squibb and Pfizer to support phase 2 and phase 3 developments of andexanet alfa and apixaban in the United States and EU.
Portola may receive additional milestone payments under these agreements based on developments in the United States and the EU. Portola has completed a Biologics License Application submission with the FDA and is awaiting acceptance for filing.
The FDA assigned a Prescription Drug User Fee Act date of 17 August 2016, under an Accelerated Approval pathway. Portola plans to submit an EU application in 2017. Bristol-Myers Squibb and Pfizer continue to provide development and regulatory guidance to Portola for the andexanet alfa programme in the United States and the EU.