A Tiede1, F Abdul-Karim2, M Carcao3, P Persson4, W H O Clausen4, S Kearney5, T Matsushita6, C Negrier7, J Oldenburg8, E Santagostino9, G Young10. 1. Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 2. Hemophilia Clinic, National Blood Centre, Wilayah Persekutuan, Kuala Lumpur, Malaysia. 3. Division of Haematology/Oncology, Department of Paediatrics, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 4. Novo Nordisk A/S, Søborg, Denmark. 5. CHCMN Hemophilia and Thrombosis Center, Children's Hospital and Clinics of Minnesota, MN, USA. 6. Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan. 7. Centre Regional de Traitement de l'Hemophilie, Hopital Louis Pradel, University Claude Bernard, Lyon, France. 8. Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany. 9. Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Maggiore Hospital, IRCCS Ca Granda Foundation, Milan, Italy. 10. Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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.
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 Bpatients, 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 Bpatients 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: 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
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