Figure 3.
Animal models to estimate FVIII equivalence of nonfactor therapies. Different types of animal models have been used to estimate FVIII equivalence for nonfactor therapies. For emicizumab, a primate acquired hemophilia A model has been used21,63 and a semi-humanized mouse model for FVIII-deficiency.64 In both models, the use of an FVIII calibrator allowed to estimate the FVIII equivalence to be 10% to 20%. For fitusiran, FVIII-deficient mice displayed a strong reduction of their bleeding tendency.27 However, no FVIII calibrator curve was used to determine an FVIII equivalence. In an alternative approach using anti-antithrombin nanobodies, inhibition of antithrombin activity appeared to correspond to an FVIII equivalence of ≥20%.52 Regarding concizumab, a rabbit model for acquired hemophilia has been described.65 Also in this model, an FVIII calibrator was unavailable. Based on the observed efficiency in the cuticle bleeding model, the FVIII equivalence seems to be ≥20% FVIII.

Animal models to estimate FVIII equivalence of nonfactor therapies. Different types of animal models have been used to estimate FVIII equivalence for nonfactor therapies. For emicizumab, a primate acquired hemophilia A model has been used21,63  and a semi-humanized mouse model for FVIII-deficiency.64  In both models, the use of an FVIII calibrator allowed to estimate the FVIII equivalence to be 10% to 20%. For fitusiran, FVIII-deficient mice displayed a strong reduction of their bleeding tendency.27  However, no FVIII calibrator curve was used to determine an FVIII equivalence. In an alternative approach using anti-antithrombin nanobodies, inhibition of antithrombin activity appeared to correspond to an FVIII equivalence of ≥20%.52  Regarding concizumab, a rabbit model for acquired hemophilia has been described.65  Also in this model, an FVIII calibrator was unavailable. Based on the observed efficiency in the cuticle bleeding model, the FVIII equivalence seems to be ≥20% FVIII.

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