Abstract Number: PB1065
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: rIX-FP, recombinant factor IX (FIX) fusion protein, was developed to extend the half-life of FIX in patients with hemophilia B. Population pharmacokinetics (PPK) has been evaluated using PK data from a phase 3b study that includes extended rIX-FP dosing regimens of 100 IU/kg every 21 days for adults and 75 IU/kg every 14 days for pediatric patients.
Aims: This analysis aims to characterize the PPK of rIX-FP, assess the impact of demographic and clinical factors, and simulate FIX activity-time profiles for different dosing regimens.
Methods: Patient blood samples were collected from 113 patients with hemophilia B (FIX ≤2%) aged 1 to 70 years to determine the FIX activity. A PPK model was developed in NONMEM 7 software, where goodness-of-fit (GOF) and prediction-corrected visual predictive check (pcVPC) were used for model evaluation. Exogenous FIX activity levels were simulated for multiple dosing scenarios.
Results: FIX activity was appropriately described using a 2-compartment PPK model. The final model precision was confirmed by the GOF and pcVPC. Median exogenous rIX-FP simulated trough was approximately 5% in patients ≥12 years receiving 100 IU/kg every 21 days, approximately 5% for pediatric patients aged 6 to < 12 years, and 3% for pediatric patients aged < 6 years. Both pediatric age groups received 75 IU/kg every 14 days.
Conclusions: FIX activity-time profiles for different dosing schedules can be predicted using the PPK model. The PPK simulation data suggests that most adult and pediatric patients with hemophilia B receiving rIX-FP on 21-day and 14-day extended interval dosing regimens reach sufficient FIX activity levels to transition from severe to a mild or moderate hemophilia classification.
To cite this abstract in AMA style:
Zhang Y, McKeand W, Roberts J, Goldstein B, Tortorici MA. Population Pharmacokinetic Simulation Analysis for Extended Dosing Regimens of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Adult and Pediatric Patients with Hemophilia B [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/population-pharmacokinetic-simulation-analysis-for-extended-dosing-regimens-of-recombinant-coagulation-factor-ix-albumin-fusion-protein-rix-fp-in-adult-and-pediatric-patients-with-hemophilia-b/. Accessed April 18, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/population-pharmacokinetic-simulation-analysis-for-extended-dosing-regimens-of-recombinant-coagulation-factor-ix-albumin-fusion-protein-rix-fp-in-adult-and-pediatric-patients-with-hemophilia-b/