Dose tailoring of human cell line-derived recombinant factor VIII simoctocog alfa: Using a limited sampling strategy in patients with severe haemophilia A

Aims The use of factor VIII (FVIII) prophylaxis in haemophilia A is considered the standard of care, particularly in children. Despite adjustment of doses for body weight and/or age, a large pharmacokinetic (PK) variability between patients has been observed. PK-tailored prophylaxis may help clinicians adjust coagulation factor FVIII activity (FVIII:C) to the desired level, which may differ in individual patients. The objective was to develop a population PK model for simoctocog alfa based on pooled clinical trial data and to develop a Bayesian estimator to allow PK parameters in individual patients to be estimated using a reduced number of blood samples. Methods PK data from 86 adults and 29 children/adolescents with severe haemophilia A were analysed. The FVIII data measured using 2 different assays (chromogenic and the 1-stage clotting assay) were fit to separate develop population PK models using nonlinear mixed-effect models. A Bayesian estimator was then developed to estimate the time above the threshold of 1%. Results The PK data for chromogenic and the 1-stage clotting assays were both best described by a 2-compartment models. Simulations demonstrated good predictive capacity. The limited sampling strategy using blood sample at 3 and 24 hours allowed an accurate estimation of the time above the threshold of 1% FVIII:C (mean bias 0.01 and 0.11, mean precision 0.18 and 0.45 for 2 assay methods). Conclusion In this study, we demonstrated that a Bayesian approach can help to reduce the number of samples required to estimate the time above the threshold of 1% FVIII:C with good accuracy.