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Portola Pharmaceuticals Announces Phase 3 ANNEXA(TM)-A Study of Andexanet Alfa and Eliquis (Apixaban) Met Primary and Secondary Endpoints With High Statistical Significance
Detailed data will be presented as an oral presentation during the "Clinical Science: Special Reports" session at the
"Andexanet alfa represents a potential important advance to the field of anticoagulation for Factor Xa inhibitor patients who suffer a major bleeding event or those requiring emergency surgery," said
"These highly statistically significant Phase 3 ANNEXA-A data demonstrate that andexanet alfa has the potential to be the first agent approved as a universal Factor Xa inhibitor antidote. We anticipate filing a Biologics License Application with the
ANNEXA-A Study Design and Results
The randomized, double-blind, placebo-controlled Phase 3 ANNEXA-A studies are evaluating the safety and efficacy of andexanet alfa in reversing Eliquis-induced anticoagulation in older healthy volunteers. Efficacy is being evaluated using biomarker endpoints, including anti-Factor Xa levels as the primary endpoint. Secondary endpoints include levels of plasma unbound (free fraction) of Eliquis and thrombin generation. In the first ANNEXA-A study, reported today, 33 older healthy volunteers were given Eliquis 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus or to placebo. The study met its primary and secondary endpoints with high statistical significance. Results showed that andexanet alfa immediately and significantly reversed the anticoagulation activity of Eliquis.
In the second ANNEXA-A study, 32 healthy volunteers will be given Eliquis 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus followed by a continuous infusion of 4 mg/min for 120 minutes or to placebo. These data are expected in early 2015.
About the Andexanet Alfa Clinical Development Program
Portola is evaluating andexanet alfa in Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies -- ANNEXA-A with
Results from three separate Phase 2 proof-of concept studies with Eliquis, XARELTO® and enoxaparin, a low molecular weight heparin and indirect Factor Xa inhibitor, 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 Phase 1 and 2 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 edoxaban is ongoing, and a Phase 2 proof-of-concept study with Portola's Factor Xa inhibitor betrixaban is planned.
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 in the G7 countries alone.
Andexanet alfa, a recombinant modified Factor Xa molecule, 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
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 B cell 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 Portola's product candidates. 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; Portola's ability to manufacture andexanet alfa; regulatory developments in
*Cerdulatinib is a proposed International Nonproprietary Name (pINN).