The second part of Portola Pharmaceuticals’ phase 3 ANNEXATM-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 US 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 (7–11 November, Orlando, USA).
“These positive topline data from part two of the ANNEXA-R study mark the successful completion of our phase 3 clinical programme 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,” says John T Curnutte, 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 one of the study demonstrated rapid reversal with a bolus infusion, and part two of the study now shows the ability of andexanet alfa to sustain that reversal. Topline data from part two show that andexanet alfa, which was administered as an intravenous 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,” continues 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 haemorrhage or requiring emergency surgery.”