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

Authors: Carcao, M; Hermans, C; Giermasz, A; Kessler, C; Miesbach, W; Quon, D; Windyga, J; Mahlangu, J

Affiliations: The Hospital for Sick Children, Toronto, Canada. Catholic University of Louvain, Hemophilia Center of the Saint-Luc University Hospital, Brussels, Belgium. UC Davis Medical Center, Sacramento, California, USA. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, USA. Goethe University Hospital, Frankfurt, Germany. Orthopaedic Hemophilia Treatment Center, Los Angeles, USA. Institute of Hematology and Transfusion Medicine, Warsaw, Poland. University of the Witwatersrand, Johannesburg, South Africa.

Publication: Haemophilia; 2025

ABSTRACT: 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 neutralizing antibodies were detected. CONCLUSIONS: These findings demonstrate favorable safety and tolerability regarding the use of the 225 μg/kg IDR. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01708564, NCT02020369, NCT02448680.