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

Summary 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 3 IU dL−1 or above 10 IU dL−1. These FVIII levels were chosen based on the observation that trough levels of 1 IU dL−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 ≥3 IU dL−1 in 57% of patients treated with rAHF‐PFM 30 IU kg−1 every 48 h compared with 41.1%, 18.3%, 0.9% and 0% of patients treated with rFVIIIFc 30 IU kg−1 every 72 h, 50 IU kg−1 every 96 h or 120 h and 65 IU kg−1 every 168 h respectively. Patients on rAHF‐PFM 30 IU kg−1 every 48 h spent more time weekly with FVIII levels above 10 IU dL−1 than those on rFVIIIFc 50 IU kg−1 every 96 h or 120 h, and 65 IU kg−1 every 168 h. 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.