Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX

Collins, Peter William ORCID: https://orcid.org/0000-0002-6410-1324, Moss, J., Knobe, K., Groth, A., Colberg, T. and Watson, E. 2012. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. Journal of Thrombosis and Haemostatis 10 (11) , pp. 2305-2312. 10.1111/jth.12000

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Abstract

Background: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. Objectives: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. Methods: A population pharmacokinetic model was developed from single-dose data derived from the first human-dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU kg−1 every third day). Plasma activity following dosing with N9-GP, rFIX and pdFIX for surgery and on-demand treatment of bleeds was also simulated. Results: A linear two-compartmental model best described the pharmacokinetic profiles of N9-GP, rFIX and pdFIX. A prophylactic regimen of 10 U kg−1 N9-GP once weekly predicted mean peak and trough levels of 18 and 4.2 U dL−1, while 40 U kg−1 once weekly predicted values of 72 and 17 U dL−1, respectively. Standard prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels of 34 and 3.9 IU dL−1 for rFIX, and mean values of 43 and 2.1 IU dL−1 for pdFIX. Additional simulations predicted significantly reduced dosing frequency and factor concentrate consumption for N9-GP vs. rFIX and pdFIX for surgery and the treatment of bleeds. Conclusions: N9-GP may allow prophylaxis, surgical dosing regimens and on-demand treatment of bleeding episodes with less frequent injections and lower factor concentrate consumption; this possibility is being investigated in prospective clinical trials.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	hemophilia B, nonacog beta pegol, pharmacokinetic modeling, prophylaxis, recombinant factor IX
Publisher:	Wiley-Blackwell
ISSN:	1538-7933
Last Modified:	24 Oct 2022 09:50
URI:	https://orca.cardiff.ac.uk/id/eprint/42320

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