Y Zhang1, J Roberts1, D Bensen-Kennedy1, I Jacobs1, E Santagostino2, C Voigt1, A Feussner3, M Morfini4, J Sidhu5. 1. Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA. 2. IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy. 3. Department of Preclinical Research and Development, CSL Behring GmbH, Marburg, Germany. 4. Haemophilia Centre, University Hospital of Florence, Florence, Italy. 5. Clinical Pharmacology and Early Development, CSL Limited, Parkville, Australia.
Abstract
Essentials The new recombinant factor IX (FIX) albumin fusion protein (rIX-FP) has a prolonged half-life. A population pharmacokinetic (PK) model was based on FIX activity levels of hemophilia B patients. The model was used to simulate different dosing scenarios of rIX-FP to help guide dosing. The population PK model supported prolonged dosing of rIX-FP with intervals of up to 2 weeks. Click to hear Prof.Makris's presentation on new treatments in hemophilia SUMMARY: Background The recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion® ) 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.
Essentials The new recombinant factor IX (FIX) albumin fusion protein (rIX-FP) has a prolonged half-life. A population pharmacokinetic (PK) model was based on FIX activity levels of hemophilia Bpatients. The model was used to simulate different dosing scenarios of rIX-FP to help guide dosing. The population PK model supported prolonged dosing of rIX-FP with intervals of up to 2 weeks. Click to hear Prof.Makris's presentation on new treatments in hemophilia SUMMARY: Background The recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion® ) 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 Bpatients, (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.
Authors: Tim Preijers; Laura Bukkems; Max van Spengler; Frank Leebeek; Marjon Cnossen; Ron Mathôt Journal: Eur J Clin Pharmacol Date: 2021-02-24 Impact factor: 2.953
Authors: T Preijers; M W F van Spengler; K Meijer; K Fijnvandraat; K Fischer; F W G Leebeek; M H Cnossen; R A A Mathôt Journal: Eur J Clin Pharmacol Date: 2021-10-15 Impact factor: 2.953
Authors: Tine M H J Goedhart; Laura H Bukkems; Michiel Coppens; Karin J Fijnvandraat; Saskia E M Schols; Roger E G Schutgens; Jeroen Eikenboom; Floor C J I Heubel-Moenen; Paula F Ypma; L Nieuwenhuizen; K Meijer; Frank W G Leebeek; Ron A A Mathôt; Marjon H Cnossen Journal: TH Open Date: 2022-02-03
Authors: Tim Preijers; Lisette M Schütte; Marieke J H A Kruip; Marjon H Cnossen; Frank W G Leebeek; Reinier M van Hest; Ron A A Mathôt Journal: Clin Pharmacokinet Date: 2021-01 Impact factor: 6.447
Authors: Alfonso Iorio; Andrea N Edginton; Victor Blanchette; Jan Blatny; Ana Boban; Marjon Cnossen; Peter Collins; Stacy E Croteau; Katheljin Fischer; Daniel P Hart; Shinya Ito; Joan Korth-Bradley; Stefan Lethagen; David Lillicrap; Mike Makris; Ron Mathôt; Massimo Morfini; Ellis J Neufeld; Jeffrey Spears Journal: Res Pract Thromb Haemost Date: 2018-05-20