Portola to Receive Upfront and Milestone Payments While Retaining Full Worldwide Rights to Andexanet Alfa
SOUTH SAN FRANCISCO, Calif., Jan. 13, 2014 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that it has entered into a second clinical collaboration agreement with Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) to study Portola's investigational Factor Xa inhibitor reversal agent, andexanet alfa* (PRT4445), with the oral Factor Xa inhibitor Eliquis® (apixaban). The original agreement, announced in November 2012, covered the conduct of a Phase 2 proof-of-concept study. Results of the Phase 2 study were presented at the 2013 Congress of the International Society on Thrombosis and Haemostasis (ISTH) and demonstrated andexanet alfa's ability to produce an immediate and either temporary or sustained reversal of the anticoagulation activity of Eliquis. The new clinical collaboration agreement will be in effect through Phase 3 studies with Eliquis and any potential U.S. and EU regulatory approval of andexanet alfa. The Phase 3 studies are expected to start in the first half of 2014.
Under this non-exclusive collaboration agreement, Portola will receive an upfront payment and is eligible to receive additional development and regulatory milestone payments. Bristol-Myers Squibb and Pfizer will continue to provide development and regulatory guidance for the program. Portola retains full, worldwide commercial rights to andexanet alfa, which was designated as a breakthrough therapy by the U.S. Food and Drug Administration (FDA) in November 2013 and for which Portola is pursuing an Accelerated Approval pathway.
"We are pleased to continue our collaboration with Bristol-Myers Squibb and Pfizer, which has been instrumental in accelerating andexanet alfa's development as a potential agent to reverse the anticoagulation effect of Eliquis," said William Lis, chief executive officer of Portola. "The FDA's recent designation of andexanet alfa as a breakthrough therapy recognizes the medical need for this antidote as well as its attributes, which distinguish it from general procoagulant approaches. Andexanet alfa is the only agent that has been shown to reverse the anticoagulation effect of Factor Xa inhibitors in humans."
Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions, and the anticoagulant market is expected to continue to grow with the adoption of novel oral anticoagulants. Clinical trial results suggest that, depending on their underlying medical condition, annually between 1 and 4 percent of these patients will experience uncontrolled bleeding, and an additional 1 percent will require emergency surgery.i Currently, there is no antidote or reversal agent approved for use against Factor Xa inhibitors. Leading clinicians have identified, and the FDA has recognized, the lack of an effective reversal agent for Factor Xa inhibitors as a significant unmet medical need.
About Andexanet Alfa*
Andexanet alfa is a first-in-class recombinant, modified Factor Xa molecule being developed as a direct reversal agent (antidote) for patients receiving a Factor Xa inhibitor who suffer an uncontrolled bleeding episode or who require emergency surgery. Andexanet alfa acts as a Factor Xa decoy that targets and sequesters with high specificity both direct and indirect 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.ii Through its mechanism of action, andexanet alfa has the potential to act as a universal antidote and address the direct cause of the patient's inhibited clotting activity without being prothrombotic.
Portola has entered into clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors, while retaining all rights to the program.
Portola has completed and reported data from a Phase 2 proof-of-concept study of andexanet alfa and Eliquis. Results showed that andexanet alfa produces immediate, dose-dependent and well-tolerated reversal of anti-Factor Xa activity. The reversal can be either temporary through the administration of an intravenous bolus or sustained by the addition of an extended infusion. This is critical in covering the multiple clinical scenarios in which a reversal agent would be needed, which could include patients suffering major uncontrolled bleeding from trauma or those needing emergency surgery.
Portola has also reported data from a Phase 2 proof-of-concept study of andexanet alfa and XARELTO® (rivaroxaban).
The Phase 2 studies, which have included more than 80 volunteers, have shown that andexanet alfa is well tolerated, with no thrombotic events, serious adverse events or antibodies to Factor Xa or Factor X observed.
Additional Phase 2 proof-of-concept studies with the direct Factor Xa inhibitors, betrixaban and SavaysaTM (edoxaban), and the indirect Factor Xa inhibitor, enoxaparin, are either planned or ongoing.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel therapeutics in the areas of thrombosis and hematology.
Portola's wholly-owned lead compound, betrixaban, is a novel, oral, once-daily Factor Xa inhibitor in Phase 3 development for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's properties may be uniquely suited to potentially demonstrate efficacy without significantly increasing bleeding in this patient population. Currently, there is no anticoagulant approved for extended-duration VTE prophylaxis in acute medically ill patients.
Portola's second lead development candidate, andexanet alfa (PRT4445), has the potential to be a first-in-class universal antidote to directly reverse the effects of Factor Xa inhibitors in patients who suffer an uncontrolled bleeding episode or who require emergency surgery. Portola has entered into clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors, including Bristol-Myers Squibb and Pfizer (Eliquis® [apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (XARELTO® [rivaroxaban]), and Daiichi Sankyo (SavaysaTM [edoxaban]), while retaining all commercial rights to the program. Andexanet alfa has been designated as a breakthrough therapy by the U.S. Food and Drug Administration.
Cerdulatinib* (PRT2070) and PRT2607
Portola's third wholly-owned product candidate, cerdulatinib (PRT2070), is an orally available kinase inhibitor that uniquely inhibits two validated tumor proliferation pathways -- spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being studied in patients with leukemias or lymphomas with a focus on genetically-defined subtypes, as well as in patients who have failed therapy due to relapse or acquired mutations. Portola's fourth program is partnered with Biogen Idec and is focused on the development of PRT2607, a selective Syk inhibitor. For more information, visit www.portola.com.
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: Portola's plans for future clinical studies and pursuit of an Accelerated Approval process for andexanet alfa, anticipated growth in the market for anticoagulants, and the potential efficacy, safety and activity of andexanet alfa, betrixaban and cerdulatinib. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to initiate and/or complete its clinical trials; the success of Portola's clinical trials and the demonstrated efficacy of Portola's product candidates thereunder; the accuracy of Portola's estimates regarding its expenses and capital requirements; regulatory developments in the United States and foreign countries; Portola's ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Portola's most recent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Portola undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
*Andexanet alfa and cerdulatinib are proposed International Nonproprietary Names (pINN).
iRivaroxaban ROCKET (3.6% TIMI Major); Apixaban ARISTOTLE (2.1% ISTH Major, 0.96 TIMI Major); Levi, Blood. 2008;111:4471-4476; Circulation. 2012;126:343-348.
iiLu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nature Medicine. Published online March 3, 2013.