Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real life and comparison with non-extended half-life FVIII concentrates

Authors : Pouplard, C., Sattler, L., Ryman, A., Eschwege, V., de, Maistre E., Flaujac, C., Szymezak, J., Grand, F., Repesse, Y., Galinat, H., Donnard, M., Ternisien, C., Iorio, A., Chelle, P., and Jeanpierre, E.

Publication : Haemophilia March 2020

Affiliations : Universite de Tours, Tours, France ; Service d’Hematologie-Hemostase, CHU de Tours, Tours, France ; Laboraoire d’Hematologie, CHU de Strasbourg, Strasbourg, France ; Service d’Hematologie Biologique, CHU de Bordeaux, Bordeaux, France ; Service d’Hematologie Biologique, CHU Nancy, Nancy, France ; Service d’Hematologie Biologique, CHU Dijon, Dijon, France ; Laboratoire d’Hematologie, Centre Hospitalier de Versailles, Le Chesnay, France ; Laboratoire d’Hematologie, CHU de Reims, Reims, France ; Service d’Hematologie Biologique, CHU Poitiers, Poitiers, France ; Laboratoire d’Hematologie, CHU de Caen, Caen, France ; Laboratoire d’Hematologie, CHU de Limoge, Limoge, France ; laboratoire d’Hemostase, Service d’Hematologie Biologique, CHU de Nantes, Nantes, France ; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada ; Department of Medicine, McMaster University, Hamilton, ON, Canada ; School of Pharmacy, University of Waterloo, Waterloo, ON, Canada ; Laboratoire d’Hemostase Hemobiologie, CHU de Lille, Lille, France.

Abstract: The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII-Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non-EHL FVIII. The in vivo recovery (IVR) of rFVIII-Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8 IU/mL per IU/kg, respectively. The median half-life (T1/2 ) of rFVIII-Fc was 14.5 hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels (r = .76). Both IVR and T1/2 were lower in patients under 12 years old (2.4 IU/mL per IU/kg and 11.1 hours, respectively; CSA). PK study of rFVIII-Fc vs non-EHL FVIII showed a T1/2 ratio of 1.4 in favour of rFVIII-Fc, regardless of the patient’s age. However the relative increase in T1/2 with rFVIII-Fc was lower than 30% in one-third of patients evaluated, particularly when the previous FVIII administered was a BHK-derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.