Brief Reports
Vol. 5 No. 1 (2026)
https://doi.org/10.4081/btvb.2026.413

Pharmacokinetics of extended half-life albumin-fused factor IX and heterogeneous F9 variants in hemophilia B: a retrospective cohort study

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Published: 2 March 2026
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Hemophilia B, F9 variants, extended half-life rFIX, pharmacokinetics, clearance

Authors

Barbara Lunghi
Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
Massimo Morfini
Italian Association or Hemophilia Centers (AICE), Milan, Italy.
Silvia Linari
Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy.
Dario Balestra
Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
Alessio Branchini
Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
Lisa Pieri
Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy.
Donata Belvini
Oncohematology-Oncologic Institute of Veneto, Castelfranco Veneto Hospital, Castelfranco Veneto, Italy.
Laura Banov
Thrombosis and Hemostasis Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Cristina Santoro
Department of Hematology, University Hospital Policlinico Umberto I, Rome, Italy.
Giancarlo Castaman
Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy.
Francesco Bernardi
francesco.bernardi@unife.it
https://orcid.org/0000-0003-0305-2212
Department of Life Sciences and Biotechnology, University of Ferrara, Italy.

No information is available about the influence exerted by F9 variants on extended half-life (EHL)-recombinant factor IX (rFIX) pharmacokinetics (PK). Adult patients with severe HB (n=41), infused with EHL albumin-fused-rIX-FP, were investigated for key parameters, obtained by Non-Compartmental Analysis (NCA), and for F9 variants, grouped by non-null (n=27) and null (n=14) lesions. Distribution of PK parameters did not differ between genotype groups. However, clearance in the first tertile, including favorable PK profiles, was slower (p=0.003) in patients with null (mean 0.52 mL/h/kg) than in non-null (mean 0.62 mL/h/kg) variants, and non-null genotypes were more frequent in the third tertile (p=0.046). Missense variant bioinformatics analyses predicted more severe disease features in the third than in the first tertile. These exploratory results suggest i) a moderate role of F9 variant type in inter-individual EHL-rFIX clearance variability and ii) differences in F9 genotype-PK NCA parameter association between EHL- and standard half-life-rFIX products.

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Ethics Approval

Patients with severe HB were enrolled in a global phase 3 study (www.clinicaltrials.gov, #NCT0101496274), Italian Association of Hemophilia Centres (AICE) initiatives (Genotype-Phenotype PK Study, GePKHIS, EudraCT ID2017‐003902–42)

CRediT authorship contribution

Massimo Morfini, Giancarlo Castaman, Francesco Bernardi, conception and design; Barbara Lunghi, Silvia Linari, Dario Balestra, Alessio Branchini, Lisa Pieri, Donata Belvini, Laura Banov, Cristina Santoro, data analysis and interpretation; Barbara Lunghi, Massimo Morfini, Giancarlo Castaman, Francesco Bernardi, writing – manuscript drafting; all authors, writing – manuscript review for important intellectual content. All authors have read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work.

Supporting Agencies

European Union – NextGenerationEU

Data Availability Statement

All relevant data are included in the manuscript. Further original data will be made available by contacting the corresponding author within the regulations of the ethical approval.  

How to Cite



1.
Lunghi B, Morfini M, Linari S, Balestra D, Branchini A, Pieri L, et al. Pharmacokinetics of extended half-life albumin-fused factor IX and heterogeneous F9 variants in hemophilia B: a retrospective cohort study. Bleeding Thromb Vasc Biol [Internet]. 2026 Mar. 2 [cited 2026 Apr. 25];5(1). Available from: https://www.btvb.org/btvb/article/view/413
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