Abstract Number: PB0223
Meeting: ISTH 2022 Congress
Background: Mim8 is a factor IXa/factor X (FIXa/FX) bispecific antibody (BiAb) that demonstrates superior hemostatic properties in vitro and in hemophilia A (HA) mouse models compared with emicizumab. HA patients without inhibitors treated with a BiAb may require concomitant administration of factor VIII (FVIII), for treatment of breakthrough bleeds or surgeries. Both molecules compete for the same substrates; therefore, to evaluate the hemostatic potential of Mim8 and FVIII combined, we performed the thrombin generation test (TGT) with different activators.
Aims: To evaluate the effect of Mim8+FVIII over a broad range of concentrations in severe HA plasma, using tissue factor (TF) and factor XIa (FXIa) as activators in TGT.
Methods: Thrombin generation was evaluated in severe HA plasma with added FVIII and Mim8 at concentrations between 0–2 IU/ml and 3–100 nM, respectively. TGT was initiated by 0.001 and 0.008 U/mL FXIa, or 1 pM TF.
Results: When evaluating the concentration response for FVIII or Mim8 in TGT, the amount of thrombin generated appeared dependent on the amount of FIXa generated by the activator. The effect of combining Mim8 and FVIII was similar across all respective activation conditions tested. For all Mim8 concentrations tested, an additive effect was observed for thrombin generation when combining with up to 0.3 IU/mL FVIII. At higher FVIII concentrations, thrombin generation was similar or slightly lower compared to samples without Mim8 (Figure 1).
Conclusion(s): Mim8 does not affect FVIII function in hemophilia A, thus per-label FVIII doses can be used with Mim8 treatment, when necessary. Our TGT data suggest that patients with FVIII plasma levels up to 0.3 IU/mL may benefit from supplemental treatment with Mim8. Above 0.3 IU/mL FVIII, the added effect of Mim8 was limited and at very high concentrations of Mim8 and FVIII there was minimal competition for substrate.
To cite this abstract in AMA style:Lund J, Jensen K, Ezban M. Mim8 does not affect FVIII function in hemophilia A [abstract]. https://abstracts.isth.org/abstract/mim8-does-not-affect-fviii-function-in-hemophilia-a/. Accessed November 30, 2023.
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