title: Population pharmacokinetics of a new long-acting recombinant coagulation factor IX albumin fusion protein for patients with severe hemophilia B.
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-1for 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-1for the duration of the dosing interval for the 25, 35 and 40 IU kg-1weekly regimens and for 75 IU kg-1every 14 days in adolescents/adults, and for the 35 and 40 IU kg-1weekly 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: Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA.
authors: Y
authors: Y
authors: Zhang
authors: Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA.
authors: J
authors: J
authors: Roberts
authors: Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA.
authors: D
authors: D
authors: Bensen-Kennedy
authors: Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA.
authors: I
authors: I
authors: Jacobs
authors: IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy.
authors: E
authors: E
authors: Santagostino
authors: Clinical Pharmacology and Early Development, CSL Behring, King of Prussia, PA, USA.
authors: C
authors: C
authors: Voigt
authors: Department of Preclinical Research and Development, CSL Behring GmbH, Marburg, Germany.
authors: A
authors: A
authors: Feussner
authors: Haemophilia Centre, University Hospital of Florence, Florence, Italy.
authors: M
authors: M
authors: Morfini
authors: Clinical Pharmacology and Early Development, CSL Limited, Parkville, Australia.
authors: J
authors: J
authors: Sidhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000418:Albumins / Q000737:chemistry / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D005164:Factor IX / Q000737:chemistry / Q000493:pharmacokinetics*; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000418:Albumins; D011993:Recombinant Fusion Proteins; D005164:Factor IX
keywords: children; factor IX; hemophilia B; pharmacokinetics; recombinant proteins