Association between FIX levels & bleeding rates in hemophilia B patients receiving rFIXFc or N9-GP

Introduction Extended half-life (EHL) factor IX (FIX) concentrates reduce treatment burden and improve outcomes over standard half-life FIX. Differences in EHL pharmacokinetic (PK)/pharmacodynamic properties suggest that plasma FIX levels may not completely explain hemostatic control levels. The aim is to explore the association between plasma FIX levels and bleeding rates in people with hemophilia B (PWHB) treated with rFIXFc or N9-GP. Method Retrospective analysis of PWHB treated with rFIXFc (2016–2018) or N9-GP (2018 onward) for≥3 months using data from Canadian Bleeding Disorders Registry (CBDR) and Web-Accessible Pharmacokinetic Service-Hemophilia (WAPPS) platform. Bayesian predictive analysis and population PK models were used to calculate plasma FIX levels at the time of reported bleeds; shared frailty gamma model compared associations of FIX levels with bleeding rates between products. Results Among 210 PWHB in CBDR, 72 were treated with rFIXFc and 67 with N9-GP; PK data were available in WAPPS for 33 and 34 patients, respectively. rFIXFc and N9-GP were given at 1 infusion/week (median) with a median dose of 60 and 41 IU/kg, respectively. Predicted FIX plasma levels at the time of bleeding and trough levels in both bleeding and non-bleeding patients were higher for N9-GP versus rFIXFc ([ Fig. 1 ]). The association of FIX levels (per quartile) with bleeds was significantly different for each product (p=0.008 for interaction effect). The risk of spontaneous bleeding with N9-GP was higher in 2nd, 3rd, and 4th quartiles versus 1st quartile ([ Fig. 2 ]), as indicated by point estimates for hazard ratio>1. However, these estimates were highly imprecise and statistically non-significant. Fig. 1 Factor IX levels by concentrate type and bleed status in PWHB Fig. 2 Comparison of associations of FIX levels with spontaneous bleeding between rFIXFc and N9-GP after fitting an age-adjusted shared frailty model Conclusion The PK profiles of EHL FIX products can differ considerably. High plasma levels do not necessarily equate with improved bleed protection, nor may low plasma levels equate with reduced protection. For patients experiencing breakthrough bleeds at high plasma FIX levels, switching to alternative concentrates may be more effective than increased dosing. Funding: This study was funded by Sanofi. Acknowledgment: We would like to thank Sobi for their valuable review support. We would also like to thank Charu Pundir and Deepshikha Roy from Sanofi for providing the medical writing assistance. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany