Abstract
Background and objective: Tocilizumab is a recombinant, humanised monoclonal antibody of the immunoglobulin G1 (IgG1) subclass, which specifically targets the interleukin-6 receptor (IL-6R). The RGB-19 product was developed as a biosimilar to the reference medicinal product RoActemra® (authorised for use in the European Union [EU]). The current study focuses on the demonstration of structural, physico-chemical and functional similarity between RGB-19 (intravenous [IV] and subcutaneous [SC] presentations) and EU-sourced RoActemra® (IV and SC presentations). Methods: The RGB-19 biosimilar tocilizumab product was comprehensively tested using an extensive state-of-the-art analytical and functional panel of 44 methods to demonstrate similarity to the EU-sourced RoActemra®. Biosimilarity was rigorously evaluated through an extensive array of orthogonal physico-chemical and functional assays, supplemented by a detailed comparative characterisation of the primary and higher order structures of the therapeutic proteins. Results: Extensive structural analyses confirmed that the primary and higher order structures of tocilizumab proteins in RGB-19 IV and SC drug products are identical or exhibit a high degree of similarity to those of the RoActemra® reference products. The impurity profiles of RGB-19 and RoActemra® products were found to be highly comparable, as demonstrated by a series of physico-chemical techniques. A high level of similarity was shown for the most critical (soluble IL-6R binding and cell-based anti-proliferation assay) and for all other bioassay attributes. Based on the statistical evaluation, negligible differences could be detected for sialylation, glycation, fragments and charge variants, which do not affect the functional properties. Conclusion: Based on the similarity study, RGB-19 and RoActemra® can be considered highly similar drug products. The minor differences found for some physico-chemical attributes do not affect the biological potency, binding and other critical attributes, and are therefore not considered clinically meaningful.