Results of phase III/IV ANNEXA-4 study of Andexxa for reversal of anticoagulation published in NEJM.- Portola Pharma

Portola Pharmaceuticals announced full results from ANNEXA-4, the Company�s Phase IIIb/IV trial of its Factor Xa inhibitor antidote Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] in patients experiencing acute major bleeding while taking a Factor Xa inhibitor. Full data from 352 patients (249 of which were evaluable for hemostatic efficacy; all 352 were evaluable for safety) showed that Andexxa rapidly and significantly reversed anti-Factor Xa activity when administered as a bolus, and sustained this reversal when followed by a 120-minute infusion.

Anti-Factor Xa activity is a measure of the anticoagulant activity of apixaban, rivaroxaban, edoxaban and enoxaparin, the anticoagulants studied in ANNEXA-4. Among all 352 patients, 64 percent (n=227) were treated for intracranial hemorrhage (ICH) and 26 percent (n=90) were treated for a gastrointestinal bleed. Of those evaluated for efficacy 82 percent (n=204) achieved excellent or good hemostasis (stoppage of bleeding) over the 12-hour period following treatment with Andexxa, as determined by an independent adjudication committee. Within 30 days of enrollment, thrombotic events occurred in 34 patients (9.7 percent) and death occurred in 49 patients (13.9 percent), consistent with previous ANNEXA-4 trial results and with the high background thrombotic risk of the enrolled patient population. The majority of thrombotic events occurred in patients who delayed or did not re-start anticoagulation therapy with a Factor Xa inhibitor during the follow-up period. Among the 100 patients who re-started oral anticoagulation therapy, no thrombotic events were observed.

Two patients experienced an infusion reaction and none developed antibodies to Factor Xa or Factor X or neutralizing antibodies to Andexxa. Data are being presented as a late-breaking oral presentation at the International Stroke Conference 2019 and published simultaneously online by The New England Journal of Medicine (NEJM).

See: "Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors" Stuart J. Connolly et al. New England Journal of Medicine, February 7, 2019 DOI: 10.1056/NEJMoa1814051