SOUTH SAN FRANCISCO, Calif., Feb. 01, 2016 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (NASDAQ:PTLA), announced today that 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 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 in life-threatening or uncontrolled bleeding or for emergency surgery/urgent procedures. Portola retains full, worldwide commercial rights to andexanet alfa outside of Japan.
Bristol-Myers Squibb and Pfizer Agreement Details
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 2 and Phase 3 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.
Bayer Agreement Details
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 2 and Phase 3 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.
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. 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.
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.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that could significantly advance the fields of thrombosis and other hematologic diseases. The Company is advancing its three wholly-owned programs using novel biomarker and genetic approaches that may increase the likelihood of clinical, regulatory and commercial success. These programs include betrixaban, an oral, once-daily Factor Xa inhibitor being evaluated in the APEX Phase 3 study for prophylaxis of venous thromboembolism; andexanet alfa, a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable Factor Xa inhibitor; and cerdulatinib, a Syk/JAK inhibitor in development to treat hematologic cancers. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions. For more information, visit www.portola.com and follow the Company on Twitter @Portola_Pharma.
Portola Forward-looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: potential payments that may be received by Portola under these licensing agreements; the potential of these licensing arrangements to accelerate the development and commercialization of andexanet alfa in Japan; the potential of the availability of an antidote to affect prescribing behavior for Factor Xa inhibitors; continued receipt by Portola of development and regulatory support from our collaboration partners; increasing use of Factor Xa inhibitors and associated increase in patients requiring an antidote; andexanet alfa’s potential to treat patients needing reversal of Factor Xa anticoagulation effects, the projected number of patients that could benefit from andexanet alfa; the potential for andexanet alfa to become the first universal antidote for Factor Xa inhibitors; our plans for pursuit of regulatory approval of andexanet alfa, and the likelihood of clinical, regulatory and commercial success for andexanet alfa and our other product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: our expectation that we will incur losses for the foreseeable future and will need additional funds to finance our operations; we enter into collaborations that place certain aspects of the development of andexanet alfa out of our direct control; the pace of enrollment in our clinical trials; the results of our clinical trials related to the efficacy and safety of our product candidates; the risk that regulatory approval of our product candidates may not be received in a timely manner, or at all; our potential inability to manufacture andexanet alfa and our other product candidates on a commercial scale in a timely or cost-efficient manner; the accuracy of estimates regarding our expenses and capital requirements; our ability to successfully build a hospital-based sales force and commercial infrastructure; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates; and our ability to retain key scientific or management personnel. These and other risks and uncertainties are described more fully in our most recent filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K, which was filed on March 2, 2015, and Quarterly Report on Form 10-Q for the third quarter of 2015, which was filed on November 9, 2015. All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.