Portola Pharmaceuticals said today it has licensed lead development and commercial rights to its Phase III candidate andexanet alfa in Japan to Bristol-Myers Squibb (BMS) and Pfizer as an antidote for their co-marketed drug ELIQUIS® (apixaban) and other Factor Xa inhibitors.
Separately, Portola said it agreed with Bayer HealthCare to include its Factor Xa inhibitor rivaroxaban in the same clinical development program.
Portola is developing andexanet alfa for patients treated with a direct or indirect Factor Xa inhibitor when reversal of anticoagulation is needed.
Portola will retain full worldwide commercial rights to andexanet alfa outside of Japan. Within Japan, Portola aims to fill an unmet need for a universal antidote for Factor Xa inhibitors needed by some patients, as clinical use of the oral anticoagulants is growing.
While three oral Factor Xa inhibitors are now being marketed in Japan—ELIQUIS by BMS and Pfizer, rivaroxaban by Bayer HealthCare, and edoxaban by Daiichi Sankyo—no antidote has yet been approved.
“With Bristol-Myers Squibb and Pfizer leading development and commercialization activities and Bayer providing support, the path forward for andexanet alfa as a Factor Xa inhibitor antidote in Japan will be accelerated,” Portola CEO William Lis said in a statement.
BMS and Pfizer agreed to oversee all development and regulatory activities for andexanet alfa in Japan, as well as drug commercialization in Japan, subject to approval by Japan’s Ministry of Health, Labor, and Welfare (MHLW).
In return, BMS and Pfizer agreed to pay Portola a $15 million upfront, up to $20 million in potential payments tied to achieving regulatory milestones, and up to $70 million in sales-based milestone payments, as well as double-digit royalties based on andexanet alfa net sales in Japan.
Portola previously entered into two separate non-exclusive clinical collaboration agreements with BMS and Pfizer to support Phase II and Phase III development of andexanet alfa and ELIQUIS in the U.S. and EU. Portola said it may receive additional milestone payments under these agreements.
BMS and Pfizer continue to provide development and regulatory guidance to Portola for the andexanet alfa program in the U.S. and the EU.
Under its clinical collaboration with Bayer, Portola will receive $5 million up front and is eligible for an additional undisclosed milestone payment based on Japanese MHLW approval of andexanet alfa as an antidote for rivaroxaban.
Bayer agreed to provide technical support as well as fund clinical studies of andexanet alfa with rivaroxaban in Japan. However, 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, Johnson & Johnson’s Janssen Pharmaceuticals, to support Phase II and Phase III studies of andexanet alfa and rivaroxaban in the U.S. and Europe. Portola said it may also receive additional milestone payments under these agreements.
In the U.S., Portola said in December it completed a BLA submission for Andexanet alfa with the FDA and is awaiting acceptance for filing. The FDA has assigned a PDUFA target decision date of August 17, 2016, under an Accelerated Approval pathway. In Europe, Portola plans to submit a marketing authorization application in 2017.
Andexanet alfa has received the FDA’s breakthrough therapy designation.