Comprehensive Physico-chemical and Functional Similarity Assessment Study of RGB-14-P and RGB-14-X Drug Products as Proposed Biosimilars to Denosumab Reference Products.

BACKGROUND AND OBJECTIVE: Denosumab is a fully human monoclonal antibody (IgG2) k subclass that targets and binds with high affinity and specificity to receptor activator of nuclear factor-κB ligand (RANKL). Gedeon Richter's denosumab RGB-14-P and RGB-14-X are proposed biosimilar drug products to the reference medicinal products Prolia(®) and Xgeva(®) (marketing authorisation holder: Amgen Europe B.V. in the European Union [EU] and Amgen Inc. in USA, respectively). The present study demonstrates the structural, physico-chemical and functional similarity between RGB-14 and reference drug products marketed in the EU and US. METHODS: Using an extensive, state-of-the-art analytical and functional panel of 38 methods ensured the comprehensive characterisation of the biosimilar and reference drug products. To assess biosimilarity, physico-chemical and biological functional tests were performed using multiple orthogonal techniques, in addition to the in-depth comparison of the primary and higher-order structures of the therapeutic proteins. RESULTS: It has been demonstrated that the primary and higher order structures of RGB-14-P and RGB-14-X drug products are identical or highly similar to those of EU/US Prolia(®) and Xgeva(®). The purity profiles of the biosimilar and reference products were similar. Only minor differences were observed in glycosylation patterns and charge variant profiles. A wide range of bioassays was used demonstrating similarity in terms of potency, ligand and receptor binding. Additionally, during comprehensive analysis of the reference product data as the function of expiry dates, shifts were revealed in certain quality parameters, although these did not impact the biological activity of the products. CONCLUSION: The extensive analytical and functional similarity assessment study provides robust evidence that the structure and function of RGB-14-P and RGB-14-X are highly similar to those of EU/US Prolia(®) and Xgeva(®).