PB0218 - Adaptative methods using one-stage and chromogenic substrate assays for the quantitative measurement of Mim8 in human plasma

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

NM

Nathalie Martineau

R&D Supervisor
Diagnostica Stago
Gennevilliers, Ile-de-France, France
LF

Laurence Fauconnier

R&D Manager
Diagnostica Stago
Gennevilliers, Ile-de-France, France
NR

Nicole Roland

Team manager
Diagnostica Stago
Gennevilliers, Ile-de-France, France

Presenting Author(s)

Audrey Carlo, MSc

Scientific Marketing Manager
Stago
Asnières-sur-seine,, Ile-de-France, France

Co-Author(s)

TH

Tristan Hervé

Pharma Development Director
Diagnostica Stago
Asnières sur Seine, Ile-de-France, France
FD

François Depasse, PharmD, PhD

Clinical Development Director
Diagnostica Stago
Asnières Sur Seine, Ile-de-France, France
ME

Mirella Ezban

Senior Vice President Rare Disorders
NovoNordisk A/S
Copenhagen, Hovedstaden, Denmark
LN

Lydie Nicoud

R&D Director
Diagnostica Stago
Gennevilliers, Ile-de-France, France

Background: Mim8 is a new bispecific antibody that mimics the cofactor function of activated factor VIII (FVIIIa) by bridging activated factor IX (FIXa) and factor X, and enhancing the proteolytic function of FIXa to activate FX. It is currently in phase 3 clinical development for prophylaxis in patients with haemophilia A (HA), independent of inhibitor status.
Measurement of the drug concentration in a plasma sample may be useful to follow up Mim8 therapy.

Aims: Evaluate the use of Stago modified one stage assay (OSA) and chromogenic substrate assay (CSA) to determine plasma levels of Mim8.

Methods: A severe haemophilia A plasma was spiked with Mim8 at concentrations ranging from 0 to 30 µg/mL. The concentration of Mim8 samples is determined with modified FVIII:C OSA using STA-PTT Automate / STA-Deficient FVIII or STA-CK Prest / STA-ImmunoDef FVIII and a modified FVIII:C CSA using TriniCHROM Factor VIII:C (all reagents Stago, Asnières sur Seine, France) on a STAR Max analyzer (Stago). Mim8 reference material from Novo Nordisk A/S (Malov, Denmark) was used as calibrator.

Results: Recovery of measured Mim8 concentration compared to the expected target concentration is similar for the different reagents tested with modified FVIII:C OSA and modified FVIII:C CSA, with a relative difference lower than 10% in most cases (12% for the lowest Mim8 concentration tested with STA-CK Prest and STA-ImmunoDef VIII) (table 1 and figure 1).

Conclusion(s): Modified method using either aPTT or chromogenic reagents from Stago can be used to quantify Mim8 concentration in a hemophiliac plasma sample using Mim8 reference material as calibrator.