title: Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials.
abstract: BACKGROUND
  Nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (FIX) with an extended half-life developed for routine prophylaxis and the prevention and treatment of bleeding episodes in patients with haemophilia B.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the pharmacokinetics (PK) of N9-GP.
  
  
  METHODS
  Data from 41 previously treated haemophilia B patients, enrolled globally (16 adolescents/adults and 25 children; FIX activity ≤0.02 IU mL-1) with no history of FIX inhibitors, were included. N9-GP was administered once-weekly as 10 IU kg-1or 40 IU kg-1in adolescents/adults and 40 IU kg-1in children. Blood was sampled up to 168 h (1 week) post dose. Standard PK was estimated on the basis of plasma FIX activity vs. time (PK profiles) using non-compartmental methods. Furthermore, a population PK analysis and FIX activity predictions were performed.
  
  
  RESULTS
  Incremental recoveries were 0.02 (IU mL-1)/(IU kg-1) in both adolescents/adults and children. The extended half-life resulted in mean trough levels of 0.27 IU mL-1for adolescents/adults and 0.17 IU mL-1for children at steady-state after weekly dosing at 40 IU kg-1. The population PK analysis confirmed a mono-exponential decay in FIX activity and allowed for predictions of FIX activity for adolescents/adults above 0.15 IU mL-1at all times and 6.4 days week-1in children.
  
  
  CONCLUSIONS
  N9-GP has the potential to shift previously treated haemophilia B patients from a severe/moderate disease state into a mild- or non-haemophilic range for most of the dosing interval, which is expected to reduce the number of bleeding episodes.
authors.affiliation: Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-3600-8536
authors.initials: A
authors.lastname: Tiede
authors.affiliation: Hemophilia Clinic, National Blood Centre, Wilayah Persekutuan, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Abdul-Karim
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-5350-1763
authors.initials: M
authors.lastname: Carcao
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Persson
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: W H O
authors.initials: WHO
authors.lastname: Clausen
authors.affiliation: CHCMN Hemophilia and Thrombosis Center, Children's Hospital and Clinics of Minnesota, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kearney
authors.affiliation: Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Centre Regional de Traitement de l'Hemophilie, Hopital Louis Pradel, University Claude Bernard, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Negrier
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Maggiore Hospital, IRCCS Ca Granda Foundation, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Young
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002836:Hemophilia B / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D011994:Recombinant Proteins; C000592276:nonacog beta pegol; D011092:Polyethylene Glycols; D005164:Factor IX
keywords: blood coagulation disorders; extended half-life; haemophilia B; nonacog beta pegol; pharmacokinetics