Real-World Experience after Switching to FIX Extended Half Life Using Pharmacokinetic Poblacional Software and One- Compartimental MODEL

Background: New products have been developed for the prophylactic treatment of patients with haemophilia, such as extended half-life factor concentrates (EHL). These products have shown favourable pharmacokinetic (PK) properties, attaining a half-life 3 to 5-fold-longer in FIX EHL compared to standard FIX concentrates.

Aims: The aim of this study is to analyze PK parameters of severe hemophilia B patients who received prophylactic treatment with FIX-EHL: rFIX-FP and rFIXFc using two different PK models.

Methods: Multicenter, observational and prospective study. Data was collected between January 2021 and March 2022.

The PK parameters assessed were elimination rate constant (Ke; h-1), volume of distribution (Vd (dL/kg)), clearance (Cl (dL/h/kg)) and half-life time (t½). The PK assessment was performed by using the online population pharmacokinetic software WAPPS-HEMO and one-compartmental model. The pK parameters were compared between both models.

One-stage assay for FIX activity was used. Student's T- Fisher test was employed for comparison of medians using SPSS software.

Results: Fifteen patients from 3 Spanish hospitals were recruited. Nine patients were treated with rFIX-FP (median age, 33 years; median weight 60 Kg). Six patients were treated with rFIXFc (median age, 49 years; median weight, 86Kg). The mean activity-time points per patient were 3.4 and 3.2, respectively.

Using the WAPPS-HEMO population model, the PK parameters obtained for rFIX-FP versus rFIXFc were: Ke (h-1)= 0.0054 vs 0.0048 (p=0.338); Vd (mL/kg) =108.81 vs 217.41 (p<0.001); Cl (mL/h/Kg)= 0.229 vs 0.120 (p=0.331) and t ½ (h)= 135.7 vs 148.6 (p=0.428).

Using the one-compartmental model, the PK parameters of rFIX-FP versus rFIXFc were: Ke (h-1)= 0.008 vs 0.0278 (p=0.203); Vd (mL/kg) =117.29 vs 161.63 (p=0.123); Cl (mL/h/Kg)= 0.906 vs 1.59 (p=0.014) and t ½ (h)= 91.4 vs 71.9 (p=0.05).

Conclusions: There were differences in Cl and T½ when both products were evaluated using the one-compartment model. Thus, rFIX-FP t ½ was longer (91h) than rFIXFc t ½ (71.9h). Nevertheless, no differences between rFIX-FP and rFIXFc were observed using the online population pharmacokinetic software.

Alvarez Roman:Bayer: Consultancy, Honoraria, Research Funding; Biomarin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CSL-Behring: Consultancy, Honoraria, Research Funding; Novo-Nordisk: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Bosch:Roche: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria; Karyospharm: Honoraria; Takeda: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Beigene: Consultancy, Honoraria.