First Remicade® mAb biosimilar approved in Europe

Following our series of posts in biosimilars and immunogenicity testing, a recent paper by Korea company Celltrion describes the characterisation of Remsina®, the first mAb biosimilar (for Remicade® – infliximab) approved in Europe. In this study, ELISA arrays for conformational studies were used for the Higher Order Structure characterisation and compatibility analysis.

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Antibody conformation array of CT-P13 and RMP: (A) variable region (Abs 1–12); (B) constant region. Epitope exposure in both the variable and constant regions is illustrated in the figure. The error bars suggest noisy data rather than real differences between the products. All seven lots of CT-P13 were found to be consistent, as well as within the range of responses defined by the RMP, meaning that the seven CT-P13 and RMP are similar in terms of higher order structure. In contrast, another study on biosimilar mAbs using antibody array ELISA observed significant differences in higher order structure (HOS) among various biosimilar mAbs under development.

Indications for Remicade® include rheumatoid arthritis, adult Crohn’s disease, ulcerative colitis, pediatric ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. To choose the best biosimilar, Celltrion conducted extensive physicochemical characterization of Remsima® in relation to Remicade®, in order to demonstrate the highly similar properties between the two molecules. A multitude of state-of-the-art analyses revealed that Remsima® has identical primary as well as indistinguishable higher order structures compared with the original product. Monomer and aggregate contents of Remsima®were also found to be comparable with those of Remicade®.

In terms of charge isoforms, although Remsima® was observed to contain slightly less basic variants than the original antibody, the difference was shown to be largely due to the presence of C-terminal lysine. On the other hand, this lysine was found to be rapidly clipped inside serum in vitro and in vivo, suggesting it has no effect on the biological potency or safety of the drug.

Analysis of the glycan contents of the antibodies showed comparable glycan types and distributions. Recent results of clinical studies have further confirmed that the two antibody products are highly similar to each other. Based on this research as well as previous clinical and non-clinical comparability studies, Remsima®can be considered as a highly similar molecule to Remicade®in terms of physicochemical properties, efficacy, and safety for its final approval as a biosimilar product to Remicade®.

This article shows how the validation of a biosimilar has major differences with that demanded for a standard generic drug, including a wide variety of in vitro and in vivo assays, as well as clinical studies.

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