Abstract Number: VPB0206
Meeting: ISTH 2022 Congress
Background: Emicizumab is a factor (F) VIII function-mimetic anti-FIXa/X humanized bispecific monoclonal antibody for use in hemophilia A patients with or without inhibitors. Although the incidence of anti-drug antibodies (ADAs) to emicizumab is low, caution should be exercised in loss of efficacy due to ADAs. Further characterization of the ADAs (e.g. epitope analysis) would be useful.
Aims: To characterize ADAs using repository samples from ADA-positive subjects/patients in phase I, phase I/II and bioavailability studies conducted in Japan.
Methods: This research was conducted in accordance with relevant ethical standards. Neutralizing activity of ADAs against emicizumab was measured in 10 subjects/patients who tested positive for ADAs in the clinical studies, and epitope analysis was performed in 8 of these subjects/patients. Neutralizing activity was assessed by a modified Bethesda assay using FVIII-deficient plasma spiked with emicizumab, and epitope analysis was assessed by an electrochemiluminescence immunoassay.
Results: Neutralizing activity was observed in 3 subjects of 10 subjects/patients, and all epitopes were on the common light chain of emicizumab. ADAs developed in these 3 subjects were associated with decreased emicizumab exposure. Neutralizing activity could not be measured in 7 subjects/patients, including 1 subject who had decreased exposure, because ADA titers were low or the assay was affected by coexisting emicizumab. In 5 of the 7 subjects/patients for whom epitope analysis could be performed, ADAs recognized the Fab-regions (FIXa/FX-arms or FIXa-arm only) or the common light chain.
Conclusion(s): This research confirmed the neutralizing activity of ADAs in 3 subjects of 10 ADA-positive subjects/patients. The epitopes of ADAs in these 3 subjects included regions of the common light chain of emicizumab that is important to exert the pharmacological activity.
To cite this abstract in AMA style:Matsumoto N, Abe H, Kawasaki R, Tashiro Y, Noguchi M, Harada S, Yoneyama K, Niino T, Soeda T, Yoshimura Y. Characterization of Anti-Emicizumab Antibodies Using Repository Samples Obtained in Clinical Studies of Emicizumab Conducted in Japan [abstract]. https://abstracts.isth.org/abstract/characterization-of-anti-emicizumab-antibodies-using-repository-samples-obtained-in-clinical-studies-of-emicizumab-conducted-in-japan/. Accessed February 28, 2024.
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