Analytical Similarity Assessment of an Aflibercept Biosimilar SB15 to Its Commercially Available Reference Product (Eylea)

Abstract

Purpose : SB15 has been developed as a proposed biosimilar of aflibercept, for the treatment of retinal diseases including neovascular (wet) age-related macular degeneration (nAMD). The purpose of this study was the assessment of the similarity between SB15 and its commercially available reference product (RP) Eylea obtained in the United States in terms of structural and physicochemical properties and biological functions.

Methods : A characterization of structural and functional properties was conducted by state-of-the-art analytical methods. For the structural and physicochemical characterization, primary structure; higher-order structure; post-translational modifications; purity and impurities including size and charge variants; and protein concentration were compared. In addition, biological characterization including ligand binding region related and Fc-related biological activities was employed.

Results : The amino acid sequence of SB15 was identical to that of its RP. In terms of the higher-order structure, and purity and impurity in size of SB15 was concluded as similar to the RP aflibercept. In addition, SB15 and RP were similar in terms of biological activities including VEGF binding activities, potencies and Fc-related biological functions. In detail, the relative binding activities of SB15 and RP representative batches analyzed using VEGF-A 165 binding assay were evaluated as 101% (SD=5%) and 99% (SD=6%), respectively. The relative potencies by HUVEC anti-proliferation assay were 102% (SD=6%) for SB15 and 100% (SD=6%). Furthermore, the relative potencies by VEGF-A 165 neutralization assay were evaluated as 101% (SD=3%) for SB15 and 101% (SD=7%) for RP, respectively. The relative binding activities by VEGF-A 121 binding assays were 98% (SD: 2%) for SB15 and 97% (SD: 5%) for RP. The relative binding activities by FcRn binding assay were 100% (SD: 3%) for SB15 and 105% (SD: 6%) for the RP.

Conclusions : Based on comprehensive analytical similarity assessments, SB15 appears to be highly similar to the RP aflibercept in terms of structural, physicochemical and biological properties, supporting safe and effective use of SB15.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.