Population pharmacokinetics of a new long-acting recombinant coagulation factor IX albumin fusion protein for patients with severe hemophilia B

Background: The recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion (R)) exhibits a longer half-life than plasma-derived factor IX (FIX) and the commercially available recombinant FIX products. Objectives: (i) Characterize the population pharmacokinetics (PK) of rIX-FP in hemophilia B patients, (ii) identify covariates that are potential determinants of rIX-FP PK variability and (iii) simulate different dosing scenarios of rIX-FP following single and steady-state dosing. Patients/ Methods: A population PK model was developed based on FIX activity levels of 104 patients who had received treatment with rIX-FP. Patients were aged 1-65 years with FIX activity <= 2 IU dL(-1). PK sampling was performed for up to 14 days (336 h). Results: Simulation of a single intravenous infusion of rIX-FP (25-75 IU kg(-1)) predicted that the median trough exogenous FIX activity levels would remain > 5 IU dL(-1) for up to 16 days in adolescents/adults aged >= 12 years, up to 12 days in children aged 6 to < 12 years, and up to 9.5 days in children aged < 6 years. For steady-state dosing, the median trough exogenous FIX activity levels were maintained at > 5 IU dL(-1) for the duration of the dosing interval for the 25, 35 and 40 IU kg(-1) weekly regimens and for 75 IU kg(-1) every 14 days in adolescents/adults, and for the 35 and 40 IU kg(-1) weekly regimens in children. Conclusion: The population PK model developed here correlates well with observed clinical data and supports prolonged dosing of rIX-FP with intervals of up to 2 weeks.