A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B

Abstract

BackgroundRecombinant factor IX Fc fusion protein(rFIX‐Fc) is an extended half‐life (EHL) factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients ≥12 years of age.AimExternally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real world data.MethodsWe collected prospective and retrospective data from patients with haemophilia B (FIX activity level ≤5 IU/dL) treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kingdom (UK)‐EHL Outcome Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling.ResultsReal world data was obtained from 37 patients (median age: 16 years, range 2‐71) of whom 14 were <12 years of age. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction eror (MdPE) of ‐48.8%. The new model showed a lower MdPE (3.4%) and better described rFIX‐Fc PK, especially for children <12 years of age. In the new model, an increase in age was correlated with a decrease in clearance (p<0.01).ConclusionThe published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children <12 years of age. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.