Porcine recombinant factor VIII (Obizur; OBI‐1; BAX801): product characteristics and preclinical profile

Abstract

Introduction: Acquired haemophilia A (AHA) is a rare, often severe, auto‐immune bleeding disorder caused by the development of inhibitory antibodies (inhibitors) to factor VIII (FVIII). Bypassing agents, recombinant activated FVII or activated prothrombin complex concentrate, are currently recommended as first‐line treatments to control bleeding events in patients with AHA.Aim: A plasma‐derived porcine FVIII (Hyate:C, Ipsen, UK) was used as a first‐line treatment for AHA but was discontinued in 2004 due to viral safety concerns. A recombinant pFVIII (rpFVIII), Obizur (OBI‐1; BAX801), which is expected to have a similar efficacy profile to Hyate:C but with a superior safety profile was developed and recently approved by the US Food and Drug Administration for the treatment of AHA.Methods: Obizur manufacturing begins with the expression of B domain deleted rpFVIII by genetically modified baby hamster kidney‐derived cells. The final purified and lyophilized drug product has a negligible risk of viral contamination and contains no animal‐derived plasma proteins. Obizur was evaluated for immunogenicity, tolerability, pharmacokinetics and bleeding times in preclinical models including in haemophiliac dogs, cynomolgus monkeys and FVIII‐knockout mice.Results: Preclinical animal studies show that the efficacy and immunogenicity of Obizur are similar to that of Hyate:C and that Obizur has a more favourable safety profile.Conclusions: Obizur is a highly purified recombinant porcine FVIII drug product that has been demonstrated to have a favourable safety and efficacy profile when compared with Hyate:C and can be a valuable treatment option for control of bleeding in AHA patients.