Evaluation of the Structural, Physicochemical, and Biological Characteristics of SB11, as Lucentis (Ranibizumab) Biosimilar.

Introduction: SB11 was recently approved as a ranibizumab biosimilar by the US Food and Drug Administration (FDA) and the European Commission (EC) as a therapy for retinal vascular disorders under the brand name Byooviz™. This study was performed to assess the analytical similarity between SB11 and reference products from the European Union (EU-ranibizumab) and United States (US-ranibizumab).

Methods: A comprehensive structural, physicochemical, and biological characterization was performed utilizing state-of-the-art analytical methods. Comparisons included the following: primary structure related to amino acid sequence and post-translational modifications; higher order structure; product-related substances and purity/impurity including size and charge variants. In addition, biological characterization included a series of mechanism of action (MoA)-related bioassays such as vascular endothelial growth factor (VEGF)-A binding assay (VEGF-A 165 and its isoforms), cell-based VEGF-A 165 neutralization assay, and anti-proliferation assay using human umbilical vein endothelial cells (HUVEC).

Results: The amino acid sequence of SB11 was identical to that of reference products, and post-translational modification profiles and higher order structures of SB11 were shown to be indistinguishable from the reference products. Product-related size and charge variants and aggregates were also similar. Using a broad range of VEGF-related functional assays, we demonstrated that SB11 has similar biological properties to reference products in VEGF-A binding activities (VEGF-A 165 and isoforms (VEGF-A 110, VEGF-A 121, and VEGF-A 189)), VEGF-A 165 neutralization, and HUVEC anti-proliferation. Overall, SB11 exhibits high similarity compared to EU/US-ranibizumab.

Conclusion: Based on the comprehensive analytical similarity assessment, SB11 is highly similar to the EU/US-ranibizumab with respect to structural, physicochemical, and biological properties.