Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII

Introduction: Hemophilia A is routinely treated by administration of exogenous coagulation factor VIII (FVIII). As safety and efficacy of FVIII products have improved over the years, development of FVIII-neutralizing antibodies (FVIII inhibitors) has emerged as the most serious complication. The new human cell line-derived recombinant human FVIII (human-cl rhFVIII) is the first recombinant FVIII product produced in a human cell line without additive animal proteins, with a goal of minimizing the risk of inhibitor development. Materials and methods: Biochemical analyzes of purity, molecular and functional attributes of the novel human-cl rhFVIII were undertaken for product characterization. Results and conclusions: Human-cl rhFVIII was shown to be highly pure, with host-cell protein and DNA traces comparable to, or lower than, currently marketed recombinant FVIII (rFVIII) products. Human-cl rhFVIII was shown to have high specific FVIII activity and characteristics similar to full-length rFVIII products. Furthermore, no significant discrepancy between one-stage and chromogenic assay results were observed for human-cl rhFVIII, indicating potency ratios of these assays comparable to the full-length rFVIII products. In functional tests, human-cl rhFVIII exhibited physiological thrombin generation and a normal rate of inactivation by activated protein C. Importantly, human-cl rhFVIII displayed higher binding capacity with von Willebrand factor than comparator products, thus minimizing circulating unbound FVIII and further reducing the potential risk of inhibitor development. (C) 2012 Elsevier Ltd. All rights reserved.