New Topline Data From Pivotal Study Demonstrate Sustained Reversal of Anticoagulant Effect of Factor Xa Inhibitor Rivaroxaban Following Administration of Portola's FDA-Designated Breakthrough Therapy
SOUTH SAN FRANCISCO, Calif., Sept. 15, 2015 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that the second part of its Phase 3 ANNEXA™-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors – Rivaroxaban) study achieved all primary and secondary endpoints with high statistical significance. Andexanet alfa, a U.S. Food and Drug Administration (FDA)-designated breakthrough therapy, is a recombinant protein specifically designed to reverse the anticoagulant activity of Factor Xa inhibitors. Portola is developing andexanet alfa as a universal reversal agent for patients anticoagulated with an oral or injectable Factor Xa inhibitor who suffer a major bleeding episode or require emergency surgery. Full data from this part of the study have been accepted for presentation during a Late Breaking Clinical Trial session at the American Heart Association's (AHA) Scientific Sessions 2015 in November.
"These positive topline data from Part 2 of the ANNEXA-R study mark the successful completion of our Phase 3 clinical program for andexanet alfa. We believe that the findings support the potential of andexanet alfa to become the first approved universal reversal agent for Factor Xa inhibitors and a standard of care to manage major bleeding associated with these novel anticoagulants," said John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola "We now have results from both parts of each of our two Phase 3 ANNEXA studies and four parts of our Phase 2 proof-of concept, dose-finding study demonstrating that andexanet alfa can rapidly reverse the anticoagulation activity of oral and injectable Factor Xa inhibitors and sustain that reversal.
The ANNEXA-R study evaluated the safety and efficacy of andexanet alfa in reversing the anticoagulant effect of the Factor Xa inhibitor rivaroxaban, as measured by anti-Factor Xa activity, in older healthy volunteers. Part 1 of the study demonstrated rapid reversal with a bolus infusion, and Part 2 of the study now shows the ability of andexanet alfa to sustain that reversal. Topline data from Part 2 show that andexanet alfa, which was administered as an intravenous (IV) bolus followed by a continuous two-hour infusion, produced rapid reversal of the anticoagulant effect of rivaroxaban and sustained it for the duration of the infusion. In the study, andexanet alfa was well tolerated, with no serious adverse events, thrombotic events, or antibodies to Factor X or Xa reported.
"Just as with the ANNEXA-A study with apixaban, we now have clinical evidence that andexanet alfa can rapidly and significantly reverse the anticoagulant effect of rivaroxaban when administered as a bolus only or a bolus plus continuous infusion," continued Dr. Curnutte. "This means that andexanet alfa has the potential to treat patients who may need only short-duration reversal of their Factor Xa inhibitor anticoagulant as well as those who might require longer-duration reversal, such as those experiencing a severe intracranial hemorrhage or requiring emergency surgery."
About the ANNEXA-R Study
The randomized, double-blind, placebo-controlled Phase 3 ANNEXA-R study evaluated the safety and efficacy of andexanet alfa in reversing rivaroxaban-induced anticoagulation in healthy volunteers ages 50-68 years. Efficacy was evaluated using biomarker endpoints, with anti-Factor Xa levels as the primary endpoint. Secondary endpoints included plasma levels of free unbound rivaroxaban and endogenous thrombin potential (ETP), a measure of thrombin generation.
In Part 1, 41 healthy volunteers were given rivaroxaban 20 mg once daily for four days to steady state. They were then randomized in a 2:1 ratio to receive either andexanet alfa administered as an 800 mg IV bolus (n=27) or placebo (n=14).
Full results of Part 1 were presented at the American College of Cardiology's (ACC) 64th Annual Scientific Session in March 2015. Part 1 met all primary and secondary endpoints with high statistical significance. Results demonstrated that andexanet alfa rapidly and significantly reversed the anticoagulant effect of rivaroxaban as measured by anti-Factor Xa activity (>90 percent reduction of mean anti-Factor Xa activity within five minutes of the end of administration) compared with placebo (p<0.0001). Additionally, there was a significant reduction in the level of free (unbound) rivaroxaban in the plasma, and thrombin generation was rapidly restored to within the normal baseline range following administration of andexanet alfa. Andexanet alfa was well tolerated, with no serious or severe adverse events, no thrombotic events, and no antibodies to Factor X or Xa observed.
In Part 2, 39 healthy volunteers were given rivaroxaban 20 mg once daily for four days and were then randomized in a 2:1 ratio to receive either andexanet alfa administered as an 800 mg IV bolus followed by a continuous infusion of 8 mg/min for 120 minutes (n=26) or placebo (n=13). Part 2 of ANNEXA-R met all the primary and secondary endpoints with high statistical significance.
Full data from Part 2 of the ANNEXA–R study have been accepted for presentation during a Late Breaking Clinical Trial session at the American Heart Association's (AHA) Scientific Sessions 2015 in November.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that could significantly advance 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. These programs include betrixaban, an oral, once-daily Factor Xa inhibitor being evaluated in the APEX Phase 3 study for prophylaxis of venous thromboembolism; andexanet alfa, a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable Factor Xa inhibitor; and cerdulatinib, a Syk/JAK inhibitor in development to treat hematologic cancers. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions. 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: andexanet alfa's potential to treat patients needing reversal of Factor Xa anticoagulation effects, Portola's plans for pursuit of regulatory approval of andexanet alfa, and the likelihood of clinical, regulatory and commercial success for andexanet alfa and Portola's other 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 to the satisfaction of regulatory authorities; the accuracy of Portola's estimates regarding its expenses and capital requirements; Portola's 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 Portola's most recent filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K, which was filed on March 2, 2015, and Quarterly Report on Form 10-Q, which was filed on August 5, 2015. 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.
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