Portola Pharmaceuticals (PTLA), Bristol-Myers Squibb Co.(BMY) and Pfizer Inc. (PFE) announced results from the first part of the Phase 3 ANNEXA-A or Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors - Apixaban studies.
Andexanet alfa produced rapid and nearly complete reversal (by approximately 94 percent, p value < 0.0001) of the anticoagulant effect of Eliquis (apixaban) in healthy volunteers ages 50-75. The full data set will be presented today in an oral presentation during the "Clinical Science: Special Reports" session at the American Heart Association (AHA) 2014 Scientific Sessions in Chicago, IL.
This first part of the Phase 3 ANNEXA-A trial achieved all of its primary and secondary endpoints with statistical significance (p value < 0.0001). The trial included 33 subjects, with 24 randomized to andexanet alfa and nine to placebo. In the study, two to five minutes after completion of a bolus dose of andexanet alfa, the anticoagulant activity of Eliquis was reversed by approximately 94 percent (p value < 0.0001) compared with placebo as measured by anti-Factor Xa activity. Every subject treated with andexanet alfa had between 90 and 96 percent reversal of the anticoagulant activity of Eliquis. The reversal of anti-Factor Xa activity correlated with a significant reduction in the level of free, unbound Eliquis in the plasma, consistent with the mechanism of action of andexanet alfa. Additionally, andexanet alfa restored thrombin generation to baseline normal levels (prior to Eliquis therapy). In this study, no serious adverse events, thrombotic events, or antibodies to Factor X or Xa were reported following andexanet alfa administration. Mild infusion reaction was reported in three subjects.
The randomized, double-blind, placebo-controlled Phase 3 ANNEXA-A study is evaluating the safety and efficacy of andexanet alfa in reversing Eliquis-induced anticoagulation in older healthy volunteers ages 50-75. 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 levels.
In the first part of the ANNEXA-A study, reported today, 33 healthy volunteers (ages 50-73) 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 (n=24) or to placebo (n=9). In the second part, 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. Data from the second study are expected in early 2015.
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