PERSEPT 1: a phase 3 trial of activated eptacog beta for on‐demand treatment of haemophilia inhibitor‐related bleeding

Haemophilia A or B patients with inhibitors have been treated with FVII a‐containing bypassing agents for over 20 years. However, due to uncertainty regarding dose response and thrombotic risk, the use of a gradual, titrated, minimal dosing strategy remains prevalent, potentially hampering early haemostasis. Aim Evaluate the dose‐dependent efficacy, safety and immunogenicity of activated eptacog beta (rh FVII a), a new recombinant inhibitor bypassing agent for the treatment of bleeding episodes ( BE s). Methods A Phase 3, randomized, cross‐over study of initial dose regimens ( IDR s) in 27 bleeding congenital haemophilia A or B subjects with inhibitors was conducted to evaluate on‐demand treatment of mild/moderate BE s. Intravenous 75 μg/kg or 225 μg/kg initial doses with 75 μg/kg subsequent doses by schedule were administered until clinical response. Results The primary endpoint was sustained clinical response within 12 hours, determined by a composite of objective and pain measures. In the 75 μg/kg IDR , 84.9% (95% CI ; 74.0%, 95.7%) of mild/moderate BE s at 12 hours were successfully treated compared to 93.2% (95% CI ; 88.1%, 98.3%) treated in the 225 μg/kg IDR . Efficacy between the IDR s was statistically different ( P <.020) in mild/moderate bleeding episodes. Both IDR s were well tolerated with no detectable immunogenic or thrombotic responses to rh FVII a or host cell proteins. Conclusion The dose‐dependent efficacy seen in this study supports individualizing the initial dose of eptacog beta to optimize clinical response. By reducing uncertainty, the PERSEPT 1 results should increase the adoption of early haemostasis as a treatment goal for clinicians who treat haemorrhage in the inhibitor population.