Portola Pharmaceuticals Enters Into Clinical Collaboration Agreement With Bayer and Janssen for Phase 3 Studies of Andexanet Alfa*, Investigational Factor Xa Inhibitor Reversal Agent, and XARELTO(R)
Portola to Receive Upfront and Milestone Payments While Retaining Full Worldwide Rights to Andexanet Alfa
SOUTH SAN FRANCISCO, Calif., Feb. 3, 2014 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that it has entered into a second clinical collaboration agreement with Bayer HealthCare and Janssen Pharmaceuticals, Inc. to evaluate its investigational Factor Xa inhibitor reversal agent, andexanet alfa*, in Phase 3 registration studies with the U.S. Food and Drug Administration (FDA)-approved oral Factor Xa inhibitor XARELTO® (rivaroxaban). Portola's original collaboration agreement with Bayer and Janssen, announced in February 2013, covered the conduct of a Phase 2 proof-of-concept study. Interim results of that study were presented in December 2013 at the 55thAmerican Society of Hematology (ASH) Annual Meeting and demonstrated that andexanet alfa can produce an immediate and dose-dependent reversal of the anticoagulation activity of XARELTO®. The new clinical collaboration agreement will be in effect through completion of Phase 3 studies with XARELTO® 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. Portola retains full, worldwide commercial rights to andexanet alfa, which was designated as a breakthrough therapy by the FDA in November 2013 and for which Portola is pursuing an Accelerated Approval pathway.
"We are pleased to continue our excellent working partnership with Bayer and Janssen, who are helping us accelerate the development of andexanet alfa, an FDA-designated breakthrough therapy. Through this expedited pathway, we have the potential to advance the investigation of this first-in-class Factor Xa inhibitor reversal agent from IND (Investigational New Drug Application) to BLA (Biologics License Application) in under four years," said William Lis, chief executive officer.
Currently, millions of patients are treated with XARELTO® and other 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, annually, between 1-4 percent of patients treated with Factor Xa inhibitors will experience major bleeding, and an additional 1 percent will require emergency surgery, depending on the patient's underlying medical condition. Currently, standard clinical measures are employed to manage these events. Development of an agent specifically designed to reverse the activity of Factor Xa inhibitors may provide an important treatment option for patients who experience a major bleeding event or require emergency surgery.
About Andexanet Alfa* (PRT 4445)
Andexanet alfa is a first-in-class recombinant, modified Factor Xa molecule being developed as a direct reversal agent for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who may 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.i Through its mechanism of action, andexanet alfa has the potential to act as a reversal agent and address the direct cause of the patient's inhibited clotting activity without being prothrombotic.
Portola has reported data from a Phase 2 proof-of-concept study of andexanet alfa and XARELTO®. Results showed that andexanet alfa can produce 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 relevant for covering the clinical scenarios in which a reversal agent would be needed, which could include patients suffering major bleeding.
Portola has also reported data from a Phase 2 proof-of-concept study of andexanet alfa and Eliquis® (apixaban).
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 Savaysa™ (edoxaban), and the indirect Factor Xa inhibitor, enoxaparin, are either planned or ongoing.
Portola has entered into multiple clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors, while retaining full worldwide rights to the andexanet alfa program. These include Phase 3 collaborations to study andexanet alfa with Bayer HealthCare and Janssen Pharmaceuticals' XARELTO® and with Bristol-Myers Squibb Company and Pfizer's Eliquis. These studies are expected to begin in the first half of 2014.
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 reversal agent to directly reverse the effects of Factor Xa inhibitors in patients who suffer a major 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 (Savaysa™ [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).
i Lu 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.