Abstract Number: PB1144
Meeting: ISTH 2020 Congress
Background: Despite the availability of non-factor treatment options, subcutaneous prophylaxis with FVIII replacement therapies is highly desirable as frequent intravenous injections are a great burden for patients.
Aims: The development of a new recombinant FVIII with outstanding subcutaneous bioavailability, maintaining full prophylactic properties compared with intravenous treatment.
Methods: Biotest’s novel recombinant FVIII proteins containing four albumin-binding domains (FVIII-ABD) were injected intravenously and subcutaneously into hemophilia A mice (n=10/group) and Göttingen minipigs (n=3/group) with Moroctocog alfa used as comparison. Blood samples taken at defined time points (0 – 240 h) after administration, were analyzed for chromogenic FVIII activity and/or FVIII antigen levels. Non-compartmental analysis was performed to determine half-life, and area under the curve (AUC) comparison was done to assess subcutaneous bioavailability.
Results: While a subcutaneous bioavailability of 15.3% (mean) and 18.6% (median) was determined for FVIII-ABD in hemophilia A mice, Moroctocog alpha was not detectable. In the Göttingen minipig model, which provides a dermal structure closer to the human setting, subcutaneous bioavailability of up to 50% was observed for FVIII-ABD, depending on the dose and formulation.
Conclusions: A next generation recombinant FVIII molecule fused to four albumin-binding domains resulted in a feasible treatment option allowing subcutaneous hemophilia A prophylaxis with the benefit of a substantial half-life extension.
To cite this abstract in AMA style:Herbener P, Schüttrumpf J, Daufenbach J, Kistner S. A Next Generation Recombinant Factor VIII for Subcutaneous Hemophilia A Prophylaxis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-next-generation-recombinant-factor-viii-for-subcutaneous-hemophilia-a-prophylaxis/. Accessed May 16, 2021.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-next-generation-recombinant-factor-viii-for-subcutaneous-hemophilia-a-prophylaxis/