Abstract
Background The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII)
concentrates differ, leading to variation in the optimal dosing regimen for the individual
patient. The aim of this study was to establish these PK differences for various EHL
FVIII concentrates by in silico simulations.
Methods FVIII level over time profiles of rFVIII-SC, BAY 81–8973, rFVIII-Fc, BAX 855, BAY
94–9027, and standard half-life (SHL) rFVIII concentrates were simulated for 1,000
severe hemophilia A patients during steady-state dosing of 40 IU/kg every 72 hours
or dosing as advised in the summary of product characteristics (SmPC).
Results Although the elimination half-life values were comparable for rFVIII-FC, BAX 855,
and BAY 94–9027, a higher area under the curve (AUC; 2,779 IU/h/dL) for BAY 94–9027
was obtained. During steady-state dosing of 40 IU/kg every 72 hours, 58.5% (rFVIII-SC),
69.3% (BAY 81–8972), 89.0% (rFVIII-Fc), 83.9% (BAX 855), and 93.7% (BAY 94–9027) of
the patients maintained a trough level of 1 IU/dL, compared with 56.0% for SHL rFVIII.
Following dosing schemes described in the SmPC, between 51.0 and 65.4% or 23.2 and
31.1% of the patients maintained a target trough level of 1 IU/dL or 3 IU/dL, respectively.
Conclusion BAY 94–9027 showed the largest increase of AUC and best target attainment compared
with SHL rFVIII, followed closely by BAX 855 and rFVIII-Fc. BAY 81–8973 and rFVIII-SC
showed smaller PK improvements. Although our analyses increase insight into the PK
of these FVIII concentrates, more studies evaluating the relation between factor levels
and bleeding risk are needed.
Keywords
factor VIII - hemophilia A - half-life
