A proposed biosimilar of eculizumab, SB12, is highly similar to both the US and EU eculizumab reference product, which treats paroxysmal nocturnal hemoglobinuria (PNH), in terms of structural, physicochemical, biophysical, and biological features, according to a new study published in BioDrugs.
Eculizumab is a complement inhibitor that has been approved by the US Food and Drug Administration (FDA).
“Compared with ABP 959 and Elizaria®, which were previously disclosed as eculizumab proposed biosimilars, the novelty of the study is that it clearly suggested similarity with a more objective and accurate similarity evaluation by analyzing a relatively large number of EU and US eculizumab RPs [reference products],” the authors said.
SB12 and the eculizumab reference product showed similar biological activity. Their performance was comparable in terms of C5 binding activity, neonatal Fc receptor binding affinity, and Fc gamma receptor binding affinity.
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Comprehensive analytical characterization confirmed that SB12 and the eculizumab reference product had identical amino acid sequences, molecular weights, sequence variants, and post-translational modifications. Moreover, they had very similar secondary and tertiary structure profiles.
Purity analysis revealed that SB12 and the eculizumab reference product had comparably low levels of high molecular weight species. The levels of immunoglobulin G species, amino acid heavy chains and light chains, 2 heavy chains, 1 light chain, and nonglycosylated heavy chain were also similar between the 2 products.
Furthermore, all samples had equivalent isoelectric point values and electropherograms, which, together with other findings, suggested similar charge heterogeneity.
The study’s authors observed 32 N-glycans in both SB12 and the eculizumab reference product. With few exceptions, the N-glycans identified were similar. The differences in N-glycan profiles might be associated with a difference in the expression system, as SB12 is produced by recombinant DNA technology in a mammalian cell line and eculizumab is produced in an murine cell line.
In addition, similar pharmacokinetic, pharmacodynamic, immunogenicity, and safety profiles were observed between SB12 and the eculizumab reference product in a previously published phase 1 study.
Reference
Kim H, Hong E, Lee J, et al. Characterization for the similarity assessment between proposed biosimilar SB12 and eculizumab reference product using a state-of-the-art analytical method. BioDrugs. Published online April 15, 2023. doi:10.1007/s40259-023-00591-9
