Wolfgang Miesbach: Direct Comparison Reveals Distinct Mechanisms Among FVIIIa Mimetics
Wolfgang Miesbach, Head of Hemostasis/Hemophilia Center at Medical Clinic 2 at University Hospital Frankfurt, shared a post on LinkedIn about a recent article by Jacob Lund et al, published in Journal of Thrombosis and Haemostasis, adding:
“Three FVIIIa mimetics, one assay system: finally comparable. FVIIIa mimetics are bispecific antibodies that stand in for factor VIII by holding FIXa and FX together so that FX can be activated. Emicizumab, denecimig (Mim8) and zemocimig (NXT007) all work this way, but their published data came from different labs, assays and reagent lots. Lund et al. have now tested all three under identical conditions (RPTH).
Binding: zemocimig holds the FIXa/FX complex most tightly (KD 0.31 nM), emicizumab intermediate (1.06 nM), denecimig only loosely (16.4 nM).
Turnover: denecimig compensates with >200-fold higher catalytic activity (29.6 vs 0.11–0.14 min⁻¹). It binds briefly, activates FX and lets go, then starts again.
Net effect: in thrombin generation in severe haemophilia A plasma, denecimig ≈ zemocimig, both clearly above emicizumab.
Two opposite design routes, hold tight or let go fast, arrive at the same haemostatic endpoint.
Worth keeping in mind: in vitro, company-sponsored, deliberately simplified system. More thrombin in a tube is not the same as better outcomes. Once generation reaches or exceeds the normal range, the questions become therapeutic window, thrombogenicity and dosing.
Congratulations to Jacob Lund and co-authors.”
Title: In vitro effects of combining Mim8 with factor VIII, FVIIa, and activated prothrombin complex concentrates in thrombin generation assays
Authors: Jacob Lund, Kasper Jensen, Laurent Burnier, Mirella Ezban
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