Treatment with Eptacog Beta (Factor VIIa, Recombinant) Results in Early Bleed Resolution for Persons with Hemophilia A or B with Inhibitors: Results of the randomized cross-over PERSEPT 1 phase 3 study

Objective Bleeding events (BEs) in persons with hemophilia A or B with inhibitors (PwHABI) impair musculoskeletal structure and function with consequent poor quality of life. An early bleed treatment and resolution is a primary goal in optimal haemophilia management. Eptacog beta (EB - HEMA Biologics and LFB) is a new bypassing agent approved in the USA for the treatment and control of BEs in adult and adolescent PwHABI. In the PERSEPT 1 clinical trial (NCT#02020369), we evaluated efficacy and safety of EB in home treatment in adults and adolescent (age ≥12 years) in different dosages. The aim was to assess the efficacy of 2 initial dose regimens of EB in the treatment of BE in the home setting in PwHABI.

Material and Methods This was a global, prospective, multicenter, controlled, randomized, cross-over phase 3 study, approved by local ethics committees and all participants gave informed consent/assent. 27 male PwHABI were randomized to either 75 µg/kg or 225 µg/kg kg initial dose regimen (IDR); patients were crossed over to the alternate IDR every 3 months. Success was defined as bleed resolution at 12 hours following the IDR, where the lower bound of the 95 % confidence interval was required to be greater than 55 %.

Results EB demonstrated dose-dependent successful clinical response in the first 24 hours with 2 IDRs (75 µg/kg IDR: q3h; and 225 µg/kg IDR: 225 µg/kg then 75 µg/kg q3h after 9 hours if necessary). The success rate at 3 hours was 84 % in the 225 µg/kg IDR compared to 29 % in the 75 µg/kg IDR. At 9 hours, sustained hemostatic efficacy from a single 225 µg/kg dose was observed (84 %) demonstrating a dose-dependent onset of action. After 12h hours 91 % [95 % CI: 84 %, 98 %, p<0.001] of all mild or moderate BEs were treated efficiently in the 225 µg/kg IDR, as did 82 % [95 % CI: 72 %, 91 %, p<0.001] in the 75 µg/kg IDR. At 9 hours, the proportion of success from the first dose in the 225 µg/kg IDR was 84.4 %.

Conclusion Both IDRs showed successful resolution of BEs. However a higher and earlier success rate was seen with the 225 µg/kg dose. These data support the concept that a larger initial thrombin burst may result in an earlier effective clot formation and earlier bleed resolution. These findings addresses the challenge of poor or limited venous access in home treatment.

Fig 1. All mild/moderate bleeds at 3 and 24 hours following the initial dose of eptacog beta. Below: 75 µg/kg and 225 µg/kg IDR for treatment of bleeding. IDR: Initial Dosing Regimen

Publication History

Article published online:
18 June 2021