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

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.