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

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.