Abstract
Purpose :
The European Commission has granted pan-EU marketing authorization for XSB-001 (as Ximluci®), a ranibizumab biosimilar, as a therapy for retinal vascular disorders. The study objective was to demonstrate that XSB-001 is a biosimilar to EU/US ranibizumab (Lucentis®) using a comprehensive set of comparative analytical assessments.
Methods :
The comparative analytical assessments included: primary structure related to amino acid sequence and post-translational modifications; higher order structure; product-related species and purity/impurity including size and charge variants. In addition, biological characterization included the following mechanism of action (MoA)-related bioassays: a vascular endothelial growth factor (VEGF)-A binding assay (VEGF-A 165 and its isoforms) using surface plasmon resonance (SPR), a cell-based VEGF-A 165 neutralization assay in HEK293 cells, and an anti-proliferation assay in human umbilical vein endothelial cells (HUVEC). The comparative analytical assessment included physicochemical and biological characterization of 18 batches of EU ranibizumab, 13 batches of US ranibizumab, and 11 representative batches of XSB-001.
Results :
The amino acid sequence of XSB-001 was identical to that of reference ranibizumab, and post-translational modification profiles and higher order structures of XSB-001 were shown to be similar to the reference products. Product-related size and charge variants and aggregates were also similar. XSB-001 had similar biological properties to reference products in terms of 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.
Conclusions :
Findings of the comprehensive comparative analytical assessments including structural, physiochemical and functional studies demonstrate that XSB-001 is highly similar to reference ranibizumab.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.