FVIII Mimetics in Hemophilia: Comparing Emicizumab, Mim8, and NXT007 – Key Insights from BIC Meeting
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, posted on LinkedIn:
”FVIII mimetics – How different are these products? Fascinating insights from Peter Lenting at the BIC meeting on the evolving landscape of FVIII-mimetic therapies․
Emicizumab – The established pioneer with proven clinical efficacy, stimulating FIXa activity ~10-fold less than FVIIIa but effectively promoting thrombin generation and fibrin formation
Mim8 – Next-generation optimization with >20,000-fold increase in FIXa proteolytic activity and 15-fold higher potency vs emicizumab in vitro
NXT007 – Enhanced affinity through novel light chain engineering, showing 30-40 fold higher affinity for FX/FXa with improved ternary complex formation
Different epitopes, different mechanisms: While all target the FIXa-FX interaction, each product has unique binding sites and kinetic properties. Mim8’s distinct epitope includes loop 333-338 (FVIIIa binding site), potentially explaining its enhanced cofactor activity.
Clinical implications beyond haemophilia A: FVIII mimetics show promise for various bleeding disorders:
– Acquired hemophilia A – bypassing FVIII inhibitors effectively
– Type 3 von Willebrand disease – addressing the associated FVIII deficiency component
– Patients with alloantibodies to VWF or FVIII
Note: Inno8 was not part of this session, as this innovative oral development was presented in a dedicated session earlier at the meeting by Jan Astermark.”
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