Pharmacokinetic study of Kovaltry in thirty-five pediatric patients aged

Abstract

Kovaltry (BAY81-8973) is an unmodified full-length factor VIII (FVIII) concentrate that enhances the pharmacokinetic (PK) profiles as compared to some other standard half-life time FVIII concentrates. However, the PK of Kovaltry in haemophiliac patients aged <12years has not been reported previously. To investigate the pharmacokinetics and clinical outcomes of Kovaltry in 35 paediatric patients aged <12years. A total of 35 boys with severe haemophilia A were enrolled from August 2019 to May 2020 in Beijing Children's Hospital. After 72-hour washout, PK tests were performed post-infusion of 50IU/kg Kovaltry in a five-timepoint assay. WinNonlin software was used to generate individual PK parameters. The dose, frequency and bleeding details were collected within the first 6months after switching to Kovaltry from other FVIII concentrates. Compared to the blood group O, patients with blood group non-O showed longer mean half-life (t1/2 ) (p<.01), lower mean clearance (CL) (p=.01) and similar in vivo recovery (IVR) (p=.51). Higher von Willebrand factor antigen (VWF:Ag) level was correlated to longer t1/2 (p<.0001) and lower CL (p<.01). IVR was correlated to body mass index (BMI) (p<.0001). Patients with trough level >3IU/dL demonstrated lower annual bleeding rate (ABR) (p<.01), annual joint bleeding rate (AJBR) (p<.01) and annual spontaneous bleeding rate (ASBR) (p<.01). This study firstly reported the PK profiles of Kovaltry in 35 paediatric patients <12years old. The great inter-individual variability of PK parameters was also confirmed in these patients. VWF:Ag and blood group were major influencing factors of t1/2 and CL of Kovaltry, while BMI was a vital predictor for IVR. Patients with high trough FVIII level in routine prophylaxis had reduced bleeding rates.