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


OBJECTIVE
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.
Queen's University Kingston, Kingston, ON, Canada.
D
D
Lillicrap
Baxalta Innovations GmbH, Vienna, Austria.
A
A
Schiviz
Baxalta Innovations GmbH, Vienna, Austria.
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C
Apostol
Baxalta US Inc., Milford, MA, USA.
P
P
Wojciechowski
Baxalta Innovations GmbH, Vienna, Austria.
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F
Horling
Baxalta US Inc., Milford, MA, USA.
C K
CK
Lai
Baxalta Innovations GmbH, Vienna, Austria.
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C
Piskernik
Baxalta Innovations GmbH, Vienna, Austria.
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W
Hoellriegl
Emory University School of Medicine, Atlanta, GA, USA.
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P
Lollar
FVIII; FVIII inhibitors; Obizur; acquired haemophilia A; bypass agents; recombinant porcine FVIII