The European Medicines Agency (EMA) has recommended granting a conditional approval for andexanet alfa (Ondexxya) as an antidote to direct factor Xa (FXa) inhibitors when reversal of anti-coagulation is needed because of life-threatening or uncontrolled bleeding.
Andexanet alfa is a recombinant modified FXa protein. In two phase 3 trials (ANNEXA-A and ANNEXA-R), andexanet alfa was shown to reverse the anti-coagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects.
In recently released findings from the ANNEXA-4 trial, andexanet alfa markedly reduced anti-FXa activity in patients presenting with acute major bleeding within 18 hours of the last dose of apixaban, rivaroxaban, edoxaban or enoxaparin.
The EMA has recommended conditional approval for the therapy in the European Union. It points out that andexanet alfa has not been investigated for scenarios where direct oral FXa inhibitors are administered before surgery or other invasive procedures, and that there is insufficient data to support its use in patients with severe bleeding related to direct-oral anticoagulants other than apixaban and rivaroxaban.
The EMA opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation.