-- Phase 3 Collaboration Agreements in Place With All Direct Factor Xa Inhibitor Manufacturers While Portola Retains All Rights to Andexanet Alfa --
SOUTH SAN FRANCISCO, Calif., July 7, 2014 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that it has entered into a second clinical collaboration agreement with Daiichi Sankyo to study andexanet alfa, Portola's investigational Factor Xa inhibitor antidote, in Phase 3 registration studies with Daiichi Sankyo's Factor Xa inhibitor edoxaban. Portola's original collaboration agreement with Daiichi Sankyo, announced in June 2013, covered the conduct of a Phase 2 proof-of-concept study, for which results are anticipated later this year. The Phase 3 edoxaban studies, known as ANNEXA™- E (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors - Edoxaban), are expected to start in 2015.
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, for which Portola is pursuing an Accelerated Approval pathway.
"We have now established Phase 3 clinical collaboration agreements with all of the manufacturers of Factor Xa inhibitors. This, combined with the FDA's designation of andexanet alfa as a breakthrough therapy, underscores the significant need for an antidote for the millions of patients currently being treated with these novel anticoagulants," said William Lis, chief executive officer. "We are pursuing an accelerated approval pathway for andexanet alfa in order to bring this novel therapy to market as quickly as possible for the benefit of patients."
About the Need for a Factor Xa Inhibitor Reversal Agent
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. Recent patient datai confirm earlier clinical trial results showing that, while most novel anticoagulants have lower bleeding rates than warfarin, serious bleeding (annually, between 1-4 percent) could still occur. Development of a specific antidote designed to reverse the anticoagulant 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
Andexanet alfa, an FDA-designated breakthrough therapy, is a first-in-class recombinant, modified Factor Xa molecule. It is 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. Andexanet alfa has the potential to address numerous clinical scenarios by allowing for flexible and controlled reversal, which can be short-acting through the administration of an IV bolus or longer-acting with the addition of an extended infusion.
About the Andexanet Alfa Clinical Development Program
Portola is evaluating andexanet alfa in Phase 3 studies with Bristol-Myers Squibb Company (BMS) and Pfizer Inc.'s Eliquis® (apixaban) and Bayer HealthCare and Janssen's XARELTO® (rivaroxaban). These randomized, double-blind, placebo-controlled studies are designed to evaluate the safety and efficacy of andexanet alfa in reversing Eliquis- or XARELTO®-induced anticoagulation rapidly after an IV bolus and sustaining that effect through a continuous infusion.
Results from three separate Phase 2 proof-of concept studies with Eliquis, XARELTO® and enoxaparin in healthy volunteers demonstrated that andexanet alfa immediately reversed the anticoagulation activity of each Factor Xa inhibitor and that the reversal could be sustained. Andexanet alfa has been shown to be well tolerated in clinical studies, which have included more than 100 healthy volunteers, with no thrombotic events or antibodies to Factor Xa or Factor X observed.
A Phase 2 proof-of-concept study with Daiichi Sankyo's Factor Xa inhibitor edoxaban is ongoing, and a Phase 2 proof-of-concept study with Portola's Factor Xa inhibitor betrixaban is planned.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that have the potential to represent significant advances in 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 of its potentially life-saving therapies. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions.
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor betrixaban is being evaluated in the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's distinct properties may have the potential to allow the agent to demonstrate efficacy without the significant increase in the rate of major bleeding that was seen in this patient population with other Factor Xa inhibitors. If approved, betrixaban could be the first anticoagulant for both hospital and post-discharge VTE prophylaxis and the standard of care in this large market of more than 20 million patients worldwide.
Portola's second product candidate in the area of thrombosis, andexanet alfa, has the potential to be a first-in-class antidote to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Andexanet alfa has been designated as a breakthrough therapy by the U.S. Food and Drug Administration. Portola has entered into clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors – Bristol-Myers Squibb and Pfizer (Eliquis® [apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (XARELTO® [rivaroxaban]), and Daiichi Sankyo (edoxaban) – while retaining all commercial rights to andexanet alfa.
Portola's product candidate in the area of hematologic cancer, cerdulatinib, is an orally available molecule that uniquely inhibits two validated tumor proliferation pathways – spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being evaluated in a Phase 1/2 proof-of-concept study 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.
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: Portola's plans for future clinical studies and pursuit of an Accelerated Approval process for andexanet alfa, anticipated growth in the market for anticoagulants, clinical trial cost, design and timing, and the potential efficacy, safety and activity of andexanet alfa. 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; our ability to manufacture andexanet alfa; 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 our most recent filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K and our Quarterly Report on Form 10-Q for the first quarter of 2014. 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.
*Cerdulatinib is a proposed International Nonproprietary Name (pINN).
i Source: Truven MARKETSCAN® Commercial, Medicare Supplemental and Medicaid Database (12 months ending June 2013).