Characterization for the Similarity Assessment between SB12 (Eculizumab Biosimilar) and Eculizumab Using State-of-the-Art Analytical Method

Background: SB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive, and Neuromyelitis Optica Spectrum Disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) positive antibody.

Objective: This study was to demonstrate structural, physicochemical, and functional similarity between SB12 and eculizumab RP using state-of-the-art analytical procedures.

Methods: Comprehensive analytical characterization was conducted with side-by-side comparison with SB12, EU and US eculizumab RP using various analytical methods (more than 40 state-of-the-art assays). Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.

Results: Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to EU and US eculizumab RP by showing qualities that met the criteria for similarity assessment set with the eculizumab RP. In the structural aspects, it was confirmed that there is no difference between post-translational modification profiles and higher order structures of SB12 compared to the reference product. Product-related size, charge variants, and aggregates were also confirmed to be similar. In case of MoA-related biological activities showed that SB12 is highly similar to EU and US eculizumab RP with respect to overall critical and non-critical quality attributes performed. Moreover, similarity of comparative binding tendency of SB12 and eculizumab RP to Fc gamma receptors and C1q was confirmed through additional characterization. Based on these results, SB12 is expected to have highly similar safety and efficacy comparable to eculizumab RP.

Conclusion: In summary, the overall characterization results show that SB12 is highly similar to EU and US eculizumab RP in terms of structural, physicochemical, biophysical, and biological attributes

Hong:Samsung Bioepis, Co., Ltd.: Current Employment. Kim:Samsung Bioepis, Co., Ltd.: Current Employment. Kim:Samsung Bioepis, Co., Ltd.: Current Employment. Yoo:Samsung Bioepis, Co., Ltd.: Current Employment. Lee:Samsung Bioepis, Co., Ltd.: Current Employment.