Pharmacokinetic parameters of simoctocog alfa in children with hemophilia A without inhibitors in real clinical practice

Abstract

In our country, experience in using simoctocog alfa in children with hemophilia A (HA) without inhibitors in real clinical practice is scarce and limited to few case reports without pharmacokinetic analysis. Aim of the study: to investigate the pharmacokinetics of simoctocog alfa in children with HA in real clinical practice. We carried out a retrospective analysis of data from medical records of children with HA treated with simoctocog alfa at a single healthcare center in the Russian Federation. For pharmacokinetic characterization of simoctocog alfa, we also measured the following parameters using the Sysmex 2000 Hematology System: factor VIII activity before the administration of simoctocog alfa, and then 4 hours and 24 hours after the infusion (one-stage clotting assay performed with Pathromtin SL reagent). All measured values were entered into the WAPPS-Hemo platform for the estimation of pharmacokinetic parameters, which were then used to calculate the expected activity of the deficient factor. Ethics committee approval was not required for this study because it involved the use of aggregated retrospective data from routine clinical practice that were fully anonymized. The study included 8 patients with severe and moderate HA. The median age at the time of pharmacokinetic study was 9 years 6 months. In most patients, 1 IU/kg of simoctocog alfa led to an increase in factor VIII activity of more than 1 %; the maximum and the minimum values were 1.7 % and 0.82 %, respectively. Four patients received adequate doses of factor concentrate (43–50 IU/kg), 1 patient received factor concentrate at an insufficient dose (22 IU/kg), and 3 patients received high doses of simoctocog alfa (60 IU/kg, 71 IU/kg and 95 IU/kg). The median ‘balanced’ half-life estimate for FVIII was 11.75 hours. The median ‘balanced’ estimates of time to reach 5 % FVIII activity (0.05 IU/mL), 2 % activity (0.02 IU/mL) (n = 5) and 1 % activity (0.01 IU/mL) (n = 3) were 53.5 hours, 71.5 hours and 82.5 hours, respectively. Our results obtained in clinical settings demonstrate that simoctocog alfa can be effectively used for prophylaxis in children with HA without inhibitors. It can be administered every other day to achieve high residual activity (at least 5 %) or every third day in patients with FVIII residual activity of at least 1 % in order to reduce the number of injections.