Reference Bevacizumab and Proposed Biosimilar Show High Similarity

A study showed that a proposed biosimilar of bevacizumab (BAT1706) comparably matches with reference bevacizumab (EU/US-sourced Avastin) in terms of physiochemical and functional qualities reviewed, according to Drugs in R&D.

A thorough physicochemical and functional similarity study is a necessary part of showing biosimilarity between a reference biologic and a proposed biosimilar and was carried out for BAR1706 and reference bevacizumab.

Reference bevacizumab is a vascular endothelial growth factor (VEGF)- targeting biologic used to treat multiple cancers, including metastatic colorectal cancer.

Study authors reported on the physiochemical and functional similarity of BAT1706 and reference bevacizumab obtained from the United States (US-bevacizumab) and the European Union (EU-bevacizumab).

First, a wide range of product qualities, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-sourced reference bevacizumab using sensitive state-of-the art analytical methods. Up to 18 lots of US-bevacizumab and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706 were evaluated.

BAT1706 presented an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-sourced reference bevacizumab. BAT1706 and EU/US-bevacizumab also showed similar post-translational modifications, glycan profiles, and change variants. Potency was evaluated through a large range of bioassays and also displayed comparably between BAT1706 and EU/US-bevacizumab, with statistical equivalence showed for VEGF-A binding and neutralizing activity.

A risked-based tier approach was used for all attributes and offers a systematic way to review analytical similarity with a high confidence level and low potential for bias.

“Greater than 90% of the measured biological activities of all BAT1706 lots fall within the range of the quality range of EU/US-bevacizumab (mean 3 AU),” said the study authors.

These results strongly back the deduction that BAT1706 shows highly similar functional properties compared with reference bevacizumab.

Furthermore, quality range and visual comparison analyses showed that BAT1706 and reference bevacizumab have identical primary structures and indistinguishable higher-order structures, and highly similar purity profiles and charge isoforms.

Small differences in the ratio of galactosylation and afucosylation were found, but not expected to affect clinical safety and efficacy.

Additionally, the stability of BAT1706 and EU/US-bevacizumab was reviewed in a series of degradation experiments. The degradation pathways and degradation rates were shown to be similar for BAT1706 and the reference bevacizumab under all conditions measured.

“In conclusion, the current demonstrated and positive regulatory biosimilarity review, regardless the minor differences were observed, but these differences were not clinical meaningful, therefore it can be concluded that overall product quality of BAT1706 can be considered highly similar to EU/US Bevacizumab,” said the study authors.

Reference

Cao D, Deng C, Wang G, et al. Physicochemical and functional similarity assessment between proposed bevacizumab biosimilar BAT1706 and reference bevacizumab Drugs R D. Published online June 26, 2023. Accessed July 26, 2023. doi:10.1007/s40268-023-00432-8