Portola Pharmaceuticals Enters Licensing Agreements Worth Up to $120 Million

Portola Pharmaceuticals recently announced it has licensed lead development and commercial rights to its investigational agent andexanet alfa in Japan to Bristol-Myers Squibb Company and Pfizer Inc. 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 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. 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 commercialization of andexanet alfa into Japan, which is a new country for us and the third largest market for Factor Xa inhibitors after the United States and EU 5 countries,” said 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 commercialization 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 FDA-designated breakthrough therapy, for patients treated with a direct or indirect Factor Xa inhibitor when reversal of anticoagulation is needed, such as in life-threatening or uncontrolled bleeding or for emergency surgery/urgent procedures. 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 $15 million and is eligible to receive potential regulatory and sales-based milestone payments totaling $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 commercializing the drug in Japan, assuming it receives regulatory approval from the Japanese Ministry of Health, Labor and Welfare (MHLW).

Portola previously entered into two separate non-exclusive clinical collaboration agreements with Bristol-Myers Squibb and Pfizer to support Phase II and Phase III development 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 EU. Portola has completed a Biologics License Application (BLA) submission with the FDA and is awaiting acceptance for filing. The FDA assigned a PFUDA date of August 17, 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 program in the United States and the EU.

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 MHLW 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 EU.

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% of patients treated with Factor Xa inhibitors may experience major bleeding, and an additional 1% may require emergency surgery. Currently, use of the Factor Xa inhibitor class in Japan is substantial and growing. Based on data from IMS Health, in the 12 months ending September 2015, sales of novel oral anticoagulants in Japan were more than $800 million. There is an unmet need for an antidote for some patients.

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.