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|Portola Pharmaceuticals Begins Enrollment in Phase 3 Study of FDA-Designated Breakthrough Therapy Andexanet Alfa and Factor Xa Inhibitor XARELTO(R)|
Second Phase 3 Study of Andexanet Alfa, Potential First-in-Class Factor Xa Inhibitor Reversal Agent, to be Conducted Under Accelerated Approval Pathway
SOUTH SAN FRANCISCO, Calif., May 12, 2014 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that enrollment has begun in a Phase 3 study to evaluate the safety and efficacy of andexanet alfa, the Company's investigational recombinant Factor Xa inhibitor reversal agent, with Bayer HealthCare and Janssen Pharmaceuticals Inc.'s Factor Xa inhibitor XARELTO® (rivaroxaban). Portola is developing andexanet alfa, an FDA-designated breakthrough therapy, as a potential first-in-class agent to reverse the anticoagulation activity of Factor Xa inhibitor-treated patients who are experiencing a major bleeding episode or who require emergency surgery.
"This Phase 3 study with XARELTO® is the second registration-enabling study that we have initiated this year under an Accelerated Approval pathway to achieve our goal of bringing andexanet alfa, an FDA-designated breakthrough therapy, to market as quickly as possible. As the number of patients taking novel oral anticoagulants has increased, so has the number of hospital visits by patients who need an antidote," said John T. Curnutte, M.D., Ph.D., executive vice president, research and development at Portola.
Phase 3 Study Design
The randomized, double-blind, placebo-controlled Phase 3 study is designed to evaluate the efficacy of andexanet alfa (initial IV bolus followed by continuous infusion) in rapidly reversing XARELTO-induced anticoagulation. The study will evaluate the efficacy of andexanet alfa in healthy volunteers (ages 50-75 years) as demonstrated by biomarker endpoints, including anti-Factor Xa levels, plasma free fraction of the anticoagulant and thrombin generation. In the first part of the study, approximately 40 healthy volunteers will be given XARELTO® 20 mg once daily and then randomized in a 2:1 ratio to andexanet alfa administered as an 800 mg IV bolus or to placebo. In the second part of the study, approximately 40 healthy volunteers will be randomized in a 2:1 ratio to andexanet alfa administered as an IV bolus followed by a continuous infusion for 120 minutes or to placebo. Study participants will be followed for up to 43 days to assess safety.
About the Need for a Factor Xa Inhibitor Reversal Agent
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. 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 the Andexanet Alfa Clinical Development Program
Earlier this year, Portola entered into Phase 3 collaboration agreements with BMS/Pfizer and Bayer HealthCare/Janssen that included upfront payments and additional potential milestone payments to cover the costs of the clinical development program with Eliquis and XARELTO®, respectively. Portola retains 100 percent worldwide commercialization rights to andexanet alfa.
Results from two Phase 2 proof-of concept studies demonstrated that andexanet alfa immediately reversed the anti-Factor Xa activity of Eliquis and XARELTO® in healthy volunteers. Andexanet alfa provided temporary reversal through the administration of an IV bolus infusion or sustained reversal with the addition of an extended infusion. In clinical practice, some patients may require short-acting reversal of their anticoagulant, while others, such as those who need emergency surgery, may require long-acting reversal. Andexanet alfa has the potential to address numerous clinical scenarios by allowing for flexible and controlled reversal. Andexanet alfa has been shown to be well tolerated in clinical studies, which have included more than 90 volunteers, with no thrombotic events or antibodies to Factor Xa or Factor X observed.
Data from a Phase 2 proof-of-concept study evaluating andexanet alfa as a reversal agent for enoxaparin, a low molecular weight heparin, will be presented at the 60th Scientific and Standardization Committee meeting of the International Society on Thrombosis and Haemostasis (ISTH) in June. A Phase 2 proof-of-concept study with Daiichi Sankyo's 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's second product candidate in the area of thrombosis, andexanet alfa, has the potential to be a first-in-class reversal agent to 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 -- 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. Andexanet alfa has been designated as a Breakthrough Therapy by the U.S. Food and Drug Administration.
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 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.
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, 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; 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, which we expect to file on or about May 12, 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).