BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies

Introduction: Recombinant factor VIII (rFVIII) products with extended half-lives, such as BAY 94-9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard-acting FVIII products. Aim: To characterize the pharmacokinetic (PK) profile of BAY 94-9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A Methods: Patients with severe haemophilia A (FVIII < 1%) with > 50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18-65 years, >= 150 EDs), PROTECT VIII (12-65 years, >= 150 EDs) and PROTECT VIII Kids (< 12 years, > 50 EDs) trials. PK parameters were assessed following a 25-IU/kg or 60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was used to assess FVIII activity. Results: Compared with sucrose-formulated rFVIII, BAY 94-9027 had reduced clearance that resulted in a similar to 1.4-fold increase in half-life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile was comparable after single-and repeated-dose administrations. Dose-proportional increases were observed between 25-and 60-IU/kg administrations. BAY 94-9027 PK characteristics were age dependent, consistent with other FVIII products. Conclusions: BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.