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Multicenter Study
. 2025 May;23(5):1516-1521.
doi: 10.1016/j.jtha.2024.12.034. Epub 2025 Jan 9.

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab

Christophe Nougier  1 , Steven W Pipe  2 , Ingrid Pabinger  3 , Claire Pouplard  4 , Roger E G Schutgens  5 , Cedric Hermans  6 , Guy Young  7 , Edison Sexton  8 , Peter Quehenberger  9 , Eve-Anne Guery  4 , Albert Huisman  5 , Marie-Astrid Van Dievoet  6 , Elizabeth Marquez  7 , Yesim Dargaud  10
Affiliations
Multicenter Study

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab

Christophe Nougier et al. J Thromb Haemost. 2025 May.

Abstract

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion factor (F)VIII linked to the D'D3 domain of von Willebrand factor and 2 XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab.

Objectives: To test whether the bovine chromogenic FVIII assay, specifically calibrated for efanesoctocog, could provide an accurate assessment of efanesoctocog activity.

Methods: Seven centers across 5 countries received 12 plasma samples to measure in triplicate using 2 calibration methods across 3 independent days. Samples (n = 6) contained either only efanesoctocog (FVIII activity [FVIII:C]= 5 to 150 IU/dL), or efanesoctocog (FVIII:C = 5 to 150 IU/dL) in combination with emicizumab (50 μg/mL; n = 5). One sample contained efanesoctocog (FVIII:C = 50 IU/dL) and a high dose of emicizumab (80 μg/mL); another sample contained efanesoctocog (FVIII:C = 50 IU/dL) with a low dose of emicizumab (20 μg/mL). Each center used its own analyzers, along with their usual reagents.

Results: Chromogenic assay (CSA) calibrated with standard calibrators highly overestimates FVIII:C. However, specific calibration with efanesoctocog enabled accurate measurement of FVIII:C, with low inter- and intra-laboratory variability, and no interference from emicizumab. All CSA reagents used in the study demonstrated low variability across different laboratories (interlaboratory coefficient of variation ranges between 9% and 20%).

Conclusion: Specific calibration of the FVIII CSA using efanesoctocog and bovine reagents allows for accurate measurement of FVIII:C in patients receiving efanesoctocog, even in the presence of emicizumab.

Keywords: chromogenic assay; efanesoctocog alfa; emicizumab; factor VIII; specific calibration.

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Conflict of interest statement

Declaration of competing interests R.E.G.S. has received speaker fees and/or research grants from Bayer, CSL, Hemab, Novartis, Novo Nordisk, Octapharma, Roche, Sobi, and Takeda. M-.A.V.D. received consultancy fees from Sobi. C.H. has received research funding from Sobi as well as honoraria/speaker’s fees from Hoffmann-La Roche, Sobi, and Sanofi. Y.D. has received consultancy and/or research grants from Bayer, CSL, Pfizer, Novo Nordisk, Octapharma, Roche, Sobi, LFB, BioMarin, Apcintex-Centessa, and Takeda. S.W.P. has served as a consultant to Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, GeneVentiv, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Roche/Genentech, Sanofi, Takeda, Spark Therapeutics, and uniQure. G.Y. has received consulting fees from ASC Biotherapeutics, BioMarin, Centessa, CSL Behring, Genentech/Roche, Hema Biologics/LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi Genzyme, Spark, and Takeda, and funds for research support from Sanofi. The remaining authors stated that they had no interests which might be perceived as posing a conflict of interest or bias with the present study.

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