ORLANDO, FL — The novel agent andexanet alfa (PRT064445, Portola Pharmaceuticals) can immediately reverse the anticoagulant effect of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer/Janssen) in older patients and continue the reversal through use of both a bolus and continuous infusion, according to newly released results[1] from the phase 3 ANNEXA series of studies.

ORLANDO, FL — The novel agent andexanet alfa (PRT064445, Portola Pharmaceuticals) can immediately reverse the anticoagulant effect of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer/Janssen) in older patients and continue the reversal through use of both a bolus and continuous infusion, according to newly released results[1] from the phase 3 ANNEXA series of studies.

As previously reported by heartwire from Medscape, part one of the ANNEXA-A trial evaluated reversal of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), whereas the ANNEXA-R trial evaluated reversal of rivaroxaban. In both, all primary and secondary efficacy end points were met, including significantly reversing anti-Xa activity, in healthy volunteers who received a bolus only of the study drug vs placebo. In part two of the evaluations, the active-drug groups also received continuous infusion; ANNEXA-A part 2 results were released earlier this year.

Findings from ANNEXA-R part 2 were presented last week at the American Heart Association (AHA) 2015 Scientific Sessions, with a summary of all phase 3 results simultaneously published in the New England Journal of Medicine[2].

In his presentation at the AHA meeting, principal investigator Dr Mark Crowther (McMaster University, Hamilton, ON) reported that in 39 healthy volunteers who received rivaroxaban for 4 days, those randomized to an initial 800-mg IV bolus followed by a 2-hour 8-mg/min infusion of andexanet alfa had a significantly greater change in anti-factor Xa compared with those who received matching placebo (P<0.0001).

And, "as in all of our previous work presented at other meetings, we did not see any toxic effects," said Crowther. He added to heartwire that "when we get [FDA] approval for this agent, we'll finally have a reversal agent that will change our approach to bleeding in these patients. Because right now, we don't have that."

Official discussant Dr Jerrold Levy (Duke University School of Medicine, Durham, NC) agreed, noting that despite the impressive safety of novel oral anticoagulants (NOACs), reversal strategies are critical for emergencies.

"For the patient who comes in bleeding, we can take the anticoagulant out of the picture with this specific reversal. But clinicians have to be clinicians and treat the patients and treat the underlying issues," added Levy.

Source: http://www.medscape.com/viewarticle/...D=900076&faf=1