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 used^21,63 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.