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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Hemophilia B
Phase III Clinical Trials
Factor IX
Half-Life
Pharmacokinetics
Hemorrhage
nonacog beta pegol
Population

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

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. / 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.

In: Haemophilia, Vol. 23, No. 4, 01.07.2017, p. 547-555.

Research output: Contribution to journalArticle

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. / 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. In: Haemophilia. 2017 ; Vol. 23, No. 4. pp. 547-555.
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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.",
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T2 - results from two phase 3 clinical trials

AU - Tiede, A.

AU - Abdul-Karim, F.

AU - Carcao, M.

AU - Persson, P.

AU - Clausen, W. H.O.

AU - Kearney, S.

AU - Matsushita, T.

AU - Negrier, C.

AU - Oldenburg, J.

AU - Santagostino, E.

AU - Young, G.

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N2 - 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.

AB - 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.

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