ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 
  • Home
  • Congress Archive
    • ISTH 2022 Congress
    • ISTH 2021 Congress
    • ISTH 2020 Congress
  • Resources
  • Search

Measuring the FVIII Mimetic Activity of the New Bispecific Antibody, Mim8, in Severe Haemophilia A Plasma Using APTT and One-stage FVIII Assays

A. Bowyer1, M. Ezban2, S. Kitchen1

1Sheffield Haemophilia and Thrombosis Centre, Sheffield, United Kingdom, 2Novo Nordisk A/S, Måløv, Denmark

Abstract Number: PB0680

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Novel Biotherapeutics in Hemophilia

Background: Mim8 is a new human bispecific antibody designed for the subcutaneous prophylactic treatment of patients with haemophilia A (HA) with or without inhibitors. Mim8 mimics the function of activated factor (F)VIII by binding FIXa and FX, to facilitate activation of FX. Mim8 can influence the results of the one-stage activated partial thromboplastin time (APTT)-based FVIII clotting assays (OSA). Therefore, modification of OSA is needed to assess Mim8 drug concentration levels.

Aims: We investigated APTT and OSA using 7 reagents in severe HA (SHA) plasma spiked with Mim8. OSA were calibrated using both human plasma and product-specific calibrators.

Methods: Mim8 was spiked into SHA plasma at 0–20µg/mL. APTT and human plasma calibrated (1/10 dilution) OSA were evaluated on either a Sysmex CS5100 or ACL TOP 700 analyser. Modified OSA were evaluated on three days with each APTT reagent using a Mim8 reference product (at 10.26µg/mL) as calibrator and 1/80 plasma dilution.

Results: The APTT with all reagents was shortened to within normal limits at 1µg/mL Mim8 (Table 1). Standard mimetic FVIII activity OSA were >250IU/dL at Mim8 concentrations above 1µg/mL (data not shown).
Mim8 reference product calibrated modified OSA demonstrated some reagent variation (Table 2). However, the between-day coefficient of variance was <20% for all reagents and Mim8 concentrations. The recovery of Mim8 compared to expected target concentration was within 22% for all reagents and Mim8 concentrations.

Table 1 Actin® APTT (s) Actin® FS APTT (s) Actin® FSL APTT (s) Pathromtin® SL APTT (s) APTT SP
APTT (s)
SynthASil® APTT (s) SynthAFax® APTT (s)
Reference range (s) 20.9-30.3 19.2-27.9 25-31.3 26.4-37.5 25.4-36.9 23.2-33.4 22.4-32.9
Mim8 0 µg/mL 105.6 82.8 92.2 138.4 102.2 119 51.3
Mim8 1 µg/mL 19.7 22.4 26 32.7 25.9 28.4 16.9
Mim8 2 µg/mL 16.6 19.4 23.2 27.5 22.5 24.9 14.9
Mim8 5 µg/mL 13.9 16.9 20.8 23.1 19.8 21.4 13.3
Mim8 8 µg/mL 12.5 15.8 19.6 22 18.2 20 12.7
Mim8 10 µg/mL 12.2 15.4 19.3 20.7 18 19.2 12.2
Mim8 15 µg/mL 11.3 14.6 18.7 19 16.6 18.3 12.1
Mim8 20 µg/mL 11.1 14.2 18.3 18.5 16.6 17.8 11.9

APTT of severe haemophilia A plasma spiked with Mim8.

Table 2 Actin®
(Mim8 µg/mL)
Actin® FS
(Mim8 µg/mL)
Actin® FSL
(Mim8 µg/mL)
Pathromtin® SL
(Mim8 µg/mL)
APTT SP
(Mim8 µg/mL)
SynthASil®
(Mim8 µg/mL)
SynthAFax®
(Mim8 µg/mL)
Mim8 0 µg/mL <0.6 <0.6 <0.6 <0.6 <1 <1 <1
Mim8 1 µg/mL 0.97 1.11 0.90 0.93 0.98 1.22 1.08
Mim8 2 µg/mL 2.00 2.19 1.97 2.20 2.16 2.24 2.28
Mim8 5 µg/mL 4.80 4.97 4.70 4.87 5.14 4.97 5.37
Mim8 8 µg/mL 8.10 8.16 8.23 8.03 8.56 8.09 8.47
Mim8 10 µg/mL 9.93 9.95 9.87 9.80 9.89 10.00 10.12
Mim8 15 µg/mL 15.77 16.24 16.10 15.73 14.93 15.47 15.38
Mim8 20 µg/mL 20.73 22.38 22.97 20.73 20.25 19.61 21.38
Mim8 reference product 10.26 µg/mL 10.40 10.55 10.23 10.40 10.07 10.23 11.14

Mim8 concentration in spiked severe haemophilia A plasma measured using modified one-stage assays and product-specific standard

Conclusions: The APTT with all reagents was shortened to within normal limits at the lowest Mim8 concentration studied; this corresponded to falsely elevated FVIII:C measurements using standard OSA. Standard OSA should not be performed in patients treated with Mim8. A modified OSA calibrated using a Mim8 calibrator enabled accurate measurement of Mim8 drug concentration and was reproducible with all APTT reagents studied.

To cite this abstract in AMA style:

Bowyer A, Ezban M, Kitchen S. Measuring the FVIII Mimetic Activity of the New Bispecific Antibody, Mim8, in Severe Haemophilia A Plasma Using APTT and One-stage FVIII Assays [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/measuring-the-fviii-mimetic-activity-of-the-new-bispecific-antibody-mim8-in-severe-haemophilia-a-plasma-using-aptt-and-one-stage-fviii-assays/. Accessed November 29, 2023.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/measuring-the-fviii-mimetic-activity-of-the-new-bispecific-antibody-mim8-in-severe-haemophilia-a-plasma-using-aptt-and-one-stage-fviii-assays/

Simple Search

Supported By:

Takeda logo

ISTH 2022 Congress site

Visit the official web site for the ISTH 2022 Virtual Congress »

  • Help & Support
  • About Us
  • Cookies & Privacy
  • Wiley Job Network
  • Terms & Conditions
  • Advertisers & Agents
Copyright © 2023 John Wiley & Sons, Inc. All Rights Reserved.
Wiley