SourceNews - Jan. 19, 2015
The primary endpoint was met in the phase III ANNEXA-R study, which evaluates the safety and efficacy of the use of andexanat alfa as an antidote for the factor Xa inhibitor rivaroxaban. Andexanet alfa is being developed as a U.S. Food and Drug Administration (FDA)- designated breakthrough therapy as a universal antidote for patients treated with oral and injectable Factor Xa inhibitors who are experiencing a major bleeding episode or who require emergency surgery.
In the randomized, double-blind, placebo-controlled ANNEXA-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors – Rivaroxaban) study, administration of andexanet alfa as an intravenous (IV) bolus, significantly and immediately reversed the steady-state anticoagulation activity of rivaroxaban and was well tolerated. The efficacy and safety was tested in 41 healthy volunteers aged 50-75 years old. They received rivaroxaban 20 mg once daily for four days and were then randomized in a 2:1 ratio to receive at Cmax either andexanet alfa administered as an 800 mg IV bolus (n=27) or to placebo (n=14). Anti-Factor Xa levels were the primary endpoint.
"Andexanet alfa is unique among the other reversal agents in development in that it has been the only agent to immediately and significantly reverse all of the key pharmacodynamic measurements of coagulation that have been agreed to with the FDA for accelerated approval. These include anti-Factor Xa levels, thrombin generation and unbound anticoagulant (free fraction). This has been demonstrated with all of the Factor Xa inhibitors studied to date – apixaban, rivaroxaban, edoxaban and enoxaparin." According to John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola.
Further data will be presented at the American College of Cardiology's (ACC) 64th Annual Scientific Session in San Diego (March 16, 2015).
The second part of the ANNEXA-R study, which is evaluating a bolus plus a continuous infusion of andexanet alfa to sustain reversal, is ongoing.
Press release Portola Pharmaceuticals January 9 2015