Safety and Use of Eptacog Beta 225 µg/kg in Patients With Haemophilia A or B With Inhibitors.

INTRODUCTION

Eptacog beta is an activated recombinant human factor VII bypassing agent approved for treating bleeding episodes (BEs) in patients aged ≥12 years with haemophilia A or B with inhibitors. Two initial dose regimens (IDRs) of either 75 or 225 µg/kg, followed by 75 µg/kg, are approved. We examined the safety of eptacog beta 225 µg/kg across completed clinical trials.

METHODS

This analysis included data from a Phase 1b trial of single doses of eptacog beta 25, 75 and 225 µg/kg in non-bleeding adults with haemophilia and pooled data from two Phase 3 trials of the 75 and 225 µg/kg IDRs for treating BEs in adolescents and adults (PERSEPT 1) and children (PERSEPT 2).

RESULTS

In the Phase 1b trial, 10 patients received a single eptacog beta infusion at each dose level. In the Phase 3 trials, 48 patients received the 75 µg/kg IDR (median 20.5 infusions/patient, range 1-137 infusions) and 50 patients received the 225 µg/kg IDR (median 14.5 infusions/patient, range 1-117 infusions). There was a similar incidence of treatment-emergent adverse events (TEAEs) across all doses (225, 75 and 25 µg/kg) in the Phase 1b trial (0.8 vs. 1.0 vs. 2.1 events per infusion, respectively) and with the 225 versus 75 µg/kg IDR in the Phase 3 studies (0.046 vs. 0.029 events per infusion, respectively). No treatment-related serious TEAEs, thromboembolic events, hypersensitivity reactions, deaths attributed to eptacog beta or neutralising antibodies were detected.

CONCLUSIONS

These findings demonstrate favourable safety and tolerability regarding the use of the 225 µg/kg IDR.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT01708564, NCT02020369, NCT02448680.