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. 2023 Nov;29(6):1633-1637.
doi: 10.1111/hae.14884. Epub 2023 Oct 12.

A next generation FVIII mimetic bispecific antibody, Mim8, the impact on non-factor VIII related haemostasis assays

Annette Elizabeth Bowyer  1 , Kieron Hickey  1 , Steve Kitchen  1 , Mirella Ezban  2
Affiliations

A next generation FVIII mimetic bispecific antibody, Mim8, the impact on non-factor VIII related haemostasis assays

Annette Elizabeth Bowyer et al. Haemophilia. 2023 Nov.

Abstract

Introduction and aims: Mim8 is a next generation bispecific antibody developed for the treatment of haemophilia A (HA). Mim8 has an increased potency compared to first generation molecules. The impact on Mim8 on non-FVIII measuring haemostasis assays was assessed in plasma containing Mim8.

Methods: Congenital severe HA plasma was spiked with increasing concentrations of Mim8 (0-20 μg/mL). 28 routine and specialist haemostasis assays were used to measure activities. These included tests for prothrombin time (PT), fibrinogen, thrombin, D-dimer, anti-Xa, heparin induced thrombocytopenia (HIT), clotting factors II-XII, factor XIII, von Willebrand factor (VWF), thrombophilia and DRVVT.

Results and conclusions: Less than 10 % difference was calculated between plasma without Mim8 and plasma spiked to 15 μg/mL Mim8 in all assays except thrombin time (-10.5%), APTT-based factor IX, XI and XII, Werfen VWF:RCo (10.6%) and Siemens LA1 (-26.4%) and LA2 (-16.9%). At the expected therapeutic steady state levels of Mim8 (5-8 μg/mL), less than 10% difference was calculated for thrombin time and Werfen VWF:RCo. APTT-based assays of FIX, XI and XII are significantly elevated in the presence of Mim8 and should not be performed. A chromogenic FIX assay could be used to accurately measure FIX activity in the presence of Mim8. There was some interference in the DRVVT method we used so local assessment of other DRVVT methods is advised. Differences in all other tests would not be predicted to affect patient management.

Keywords: Mim8; bispecific antibody; chromogenic; haemophilia; one-stage.

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References

REFERENCES

    1. Graf L. Extended half-life factor VIII and factor IX preparations. Transfus Med Hemother. 2018;45:86-91.
    1. Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822.
    1. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818.
    1. Østergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice. Blood. 2021;138(14):1258-1268.
    1. Chowdary P, Jaime F, Mahlangu J, et al. FRONTIER1: a phase 1/2 dose escalation study of a novel factor VIIIa mimetic bispecific antibody, mim8, for evaluation of safety, pharmacokinetics, and efficacy. Res Pract Thromb Haemost. 2022;6(S1):101. [abstract].

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