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

A. Tiede, F. Abdul-Karim, M. Carcao, P. Persson, W. H.O. Clausen, S. Kearney, T. Matsushita, C. Negrier, J. Oldenburg, E. Santagostino, G. Young

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Abstract

Introduction: 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. Aim: 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−1 or 40 IU kg−1 in adolescents/adults and 40 IU kg−1 in 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−1 for adolescents/adults and 0.17 IU mL−1 for 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−1 at all times and 6.4 days week−1 in children. Conclusion: 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.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalHaemophilia
Volume23
Issue number4
DOIs
Publication statusPublished - Jul 1 2017

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Keywords

  • blood coagulation disorders
  • extended half-life
  • haemophilia B
  • nonacog beta pegol
  • pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Tiede, A., Abdul-Karim, F., Carcao, M., Persson, P., Clausen, W. H. O., Kearney, S., Matsushita, T., Negrier, C., Oldenburg, J., Santagostino, E., & Young, G. (2017). 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. Haemophilia, 23(4), 547-555. https://doi.org/10.1111/hae.13191