Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A.
rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient's half-life and/or response to treatment.
Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
Pratima
P
Chowdary
Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
Emma
E
Fosbury
Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
Anne
A
Riddell
Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK; Haemophilia Centre, Great Ormond Street Hospital for Children, London, UK.
Mary
M
Mathias
FVIII; efraloctocog alfa; extended half-life factors; hemophilia A; prophylaxis; rFVIIIFc
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