Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis--new insight provided by pharmacokinetic modelling.

Abstract

The pharmacokinetics (PK) of extended half-life factor VIII (FVIII) products might allow longer dosing intervals in prophylaxis, potentially affecting its efficacy. We used published population PK models of a recombinant full-length FVIII (rAHF-PFM) and a recombinant B-domain-deleted FVIII Fc fusion product (rFVIIIFc) to assess the time spent weekly with FVIII levels below 3IUdL(-1) or above 10IUdL(-1) . These FVIII levels were chosen based on the observation that trough levels of 1IUdL(-1) may not be sufficient in all patients. This approach was applied to a simulated population of 1000 severe haemophilia A subjects with dosing regimens included in the prescribing information or evaluated in clinical trials. FVIII levels remained ≥3IUdL(-1) in 57% of patients treated with rAHF-PFM 30IUkg(-1) every 48h compared with 41.1%, 18.3%, 0.9% and 0% of patients treated with rFVIIIFc 30IUkg(-1) every 72h, 50IUkg(-1) every 96h or 120h and 65IUkg(-1) every 168h respectively. Patients on rAHF-PFM 30IUkg(-1) every 48h spent more time weekly with FVIII levels above 10IUdL(-1) than those on rFVIIIFc 50IUkg(-1) every 96h or 120h, and 65IUkg(-1) every 168h. In conclusion, PK modelling indicates that choice and dosing intervals of standard and extended half-life FVIII products require careful evaluation of individual PK to allow more time at protective levels, especially in patients with active lifestyles.