Portola Pharmaceuticals Expands Clinical Collaboration Agreement with Daiichi Sankyo Worth Up to $25 Million to Develop AndexXa™ (andexanet alfa) in Germany
SOUTH SAN FRANCISCO, Calif., Nov. 01, 2016 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals Inc.® (Nasdaq:PTLA) today announced that it has expanded its existing clinical collaboration agreement with Daiichi Sankyo to develop AndexXa™ (andexanet alfa) as an antidote for edoxaban, Daiichi Sankyo’s Factor Xa inhibitor. AndexXa is currently under EMA review for reversal of Factor Xa inhibition in patients experiencing a life-threatening or uncontrolled bleed and for patients requiring urgent or emergency surgery. As part of the updated agreement, Portola will expand the ongoing ANNEXA-4 study in bleeding patients in Germany.
“As an industry, we need to address the significant unmet medical need for managing Factor Xa inhibitor-related major bleeding by bringing to market an antidote that specifically reverses anti-Factor Xa activity, the anticoagulant mechanism of these agents. With this support from Daiichi Sankyo, we will be able to improve our ability to gather data on AndexXa as a reversal agent for edoxaban. Germany is the second largest market for Factor Xa inhibitors and one where edoxaban has experienced significant growth,” said Tao Fu, chief commercial and business officer of Portola. “Our long-standing collaboration with Daiichi Sankyo, as well as all of the other manufacturers of Factor Xa inhibitors, demonstrates the confidence these companies have in the AndexXa program.”
Under the terms of the non-exclusive agreement with Daiichi Sankyo, Portola will receive a $15 million upfront payment and is eligible to receive up to an additional $10 million upon meeting site initiation and enrollment targets. Upon AndexXa’s approval, Daiichi Sankyo will be eligible to receive a low single-digit royalty on AndexXa sales up to a total of $8 million.
Portola previously entered into nine separate non-exclusive clinical collaboration agreements with Daiichi Sankyo, BMS, Pfizer, Bayer and Janssen to support Phase 2 and registrational studies of AndexXa in the United States, Europe and Japan. Portola retains all rights, including full commercial and financial rights, for AndexXa outside of Japan.
The Urgent Need for a Factor Xa Inhibitor Antidote
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. Commensurate with the increase in the use of Factor Xa inhibitors -- for stroke prevention in atrial fibrillation; treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism; and prevention of DVT following knee or hip replacement surgery -- the number of hospital admissions due to bleeding associated with these agents continues to grow. In large randomized trials of Factor Xa inhibitors in patients with atrial fibrillation, the 30-day mortality rate in patients with intracranial hemorrhage (ICH) exceeded 40 percent. Based on the current adoption of all three Factor Xa inhibitors in the United States, this results in an estimated 300 deaths per month due to ICH related bleeding.
According to IMS Health, worldwide sales of oral Factor Xa inhibitors were $9.5 billion in the 12 months ending June 2016, a 52 percent growth over the same period of last year. In the EU5, an estimated 73,000 oral Factor Xa inhibitor-treated patients will be hospitalized this year due to major bleeding or will require urgent surgery, with half of those patients in Germany.i
ANNEXA-4 Study Design
ANNEXA-4 is a global, single-arm, open-label clinical trial designed to evaluate AndexXa (andexanet alfa), a U.S. Food and Drug Administration (FDA)-designated Breakthrough Therapy, in patients who present with an acute major bleed while receiving apixaban, edoxaban, enoxaparin or rivaroxaban. For ethical reasons, this multi-center, prospective cohort study is not randomized and all participants receive AndexXa given as a bolus dose over 30 minutes followed by a two-hour infusion. Patients receive a low or high dose depending on which Factor Xa inhibitor they have received and the time they received it. Patients are evaluated for 30 days following AndexXa administration. The co-primary efficacy endpoints are the percent change in anti-Factor Xa activity at two hours and assessment of hemostasis over 12 hours following the infusion. Hemostatic efficacy is assessed by an independent endpoint adjudication committee as either excellent, good or poor/none. To date, ANNEXA-4 has enrolled more than 150 patients with life-threatening bleeds.
AndexXa (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 potentially allowing for the restoration of normal hemostatic processes. AndexXa is the first compound being studied as an antidote for Factor Xa inhibitors that directly and specifically reverses anti-Factor Xa activity – the anticoagulant mechanism of these agents. The European Medicines Agency (EMA) completed the validation period of Portola’s Marketing Authorization Application (MAA) in August 2016 and a decision is expected in 2017.
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 three programs, including betrixaban, an oral, once-daily Factor Xa inhibitor; AndexXa™ (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.
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 the timing of our development efforts for andexanet alfa and the projected need for a Factor Xa inhibitor antidote. Risks that contribute to the uncertain nature of the forward-looking statements include the risk that our data fail to demonstrate safety and efficacy of andexanet alfa to the satisfaction of the FDA or similar regulatory authorities outside the United States, such as the EMA, and the risks that we will not successfully manufacture andexanet alfa on a commercial scale or be able to obtain the capital needed to fund our operations. These and other risks and uncertainties are described more fully in our most recent filings with the Securities and Exchange Commission, including our most recent quarterly report on Form 10-Q, which was filed on August 9, 2016. 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.
i Portola estimate based on IMS reported oral Factor Xa inhibitor sales in the EU5
Ana KaporPortola Pharmaceuticalsir@portola.com
Julie NormartW2O Groupjnormart@w2ogroup.com
Portola Pharmaceuticals, Inc.