Pharmacokinetics of a high‐purity plasma‐derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency

Hereditary factor X ( FX ) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics ( PK ) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high‐purity plasma‐derived FX concentrate (pd FX ) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. Aim This analysis assessed pd FX PK after a single 25 IU kg −1 bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [ FX :C] <5 IU dL −1 ). Methods For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on‐demand pd FX treatment and treatment of ≥1 bleed with pd FX , subjects underwent repeat PK assessment. Samples were assayed for plasma FX :C (measured using the clotting and chromogenic assays) and FX antigen. Results FX :C peaked at 0.4–0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline ( n = 16) and repeat ( n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits ( n = 31). The mean terminal half‐life and incremental recovery of pd FX was 29.4 h and 2.00 IU dL −1 per IU kg −1 respectively. Conclusion This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pd FX and provide the PK data required for the treatment of hereditary FX deficiency using pd FX replacement therapy.