Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab
Abstract Background BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key compo...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Adis, Springer Healthcare
2023-07-01
|
| Series: | Drugs in R&D |
| Online Access: | https://doi.org/10.1007/s40268-023-00432-8 |
| _version_ | 1797740723491045376 |
|---|---|
| author | Di Cao Chunping Deng Guangying Wang Xiong Mei Jianhua Xie Yuanmei Liu Yujie Liu Yili Yang Shengfeng Li Cuihua Liu |
| author_facet | Di Cao Chunping Deng Guangying Wang Xiong Mei Jianhua Xie Yuanmei Liu Yujie Liu Yili Yang Shengfeng Li Cuihua Liu |
| author_sort | Di Cao |
| collection | DOAJ |
| description | Abstract Background BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key component of demonstrating biosimilarity between a reference biologic and a proposed biosimilar. Here we report the physicochemical and functional similarity of BAT1706 and reference bevacizumab sourced from both the United States (US-bevacizumab) and the European Union (EU-bevacizumab). Method A large range of product attributes, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-bevacizumab using sensitive state-of-the-art analytical techniques. Up to 18 lots of US- and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706, were assessed. Result BAT1706 was shown to have an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-bevacizumab. BAT1706 and EU/US-bevacizumab also exhibited similar post-translational modifications, glycan profiles, and charge variants. Potency, assessed using a wide range of bioassays, was also shown to be comparable between BAT1706 and EU/US-bevacizumab, with statistical equivalence demonstrated for VEGF-A binding and neutralizing activity. Conclusion Overall, this extensive comparability exercise demonstrated BAT1706 to match EU/US-bevacizumab in terms of all physicochemical and functional attributes assessed. |
| first_indexed | 2024-03-12T14:16:30Z |
| format | Article |
| id | doaj.art-64d41053842d46c0a84d01975702167f |
| institution | Directory Open Access Journal |
| issn | 1174-5886 1179-6901 |
| language | English |
| last_indexed | 2024-03-12T14:16:30Z |
| publishDate | 2023-07-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Drugs in R&D |
| spelling | doaj.art-64d41053842d46c0a84d01975702167f2023-08-20T11:14:11ZengAdis, Springer HealthcareDrugs in R&D1174-58861179-69012023-07-0123326728810.1007/s40268-023-00432-8Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference BevacizumabDi Cao0Chunping Deng1Guangying Wang2Xiong Mei3Jianhua Xie4Yuanmei Liu5Yujie Liu6Yili Yang7Shengfeng Li8Cuihua Liu9Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Bio-Thera Solutions, Ltd.Abstract Background BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key component of demonstrating biosimilarity between a reference biologic and a proposed biosimilar. Here we report the physicochemical and functional similarity of BAT1706 and reference bevacizumab sourced from both the United States (US-bevacizumab) and the European Union (EU-bevacizumab). Method A large range of product attributes, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-bevacizumab using sensitive state-of-the-art analytical techniques. Up to 18 lots of US- and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706, were assessed. Result BAT1706 was shown to have an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-bevacizumab. BAT1706 and EU/US-bevacizumab also exhibited similar post-translational modifications, glycan profiles, and charge variants. Potency, assessed using a wide range of bioassays, was also shown to be comparable between BAT1706 and EU/US-bevacizumab, with statistical equivalence demonstrated for VEGF-A binding and neutralizing activity. Conclusion Overall, this extensive comparability exercise demonstrated BAT1706 to match EU/US-bevacizumab in terms of all physicochemical and functional attributes assessed.https://doi.org/10.1007/s40268-023-00432-8 |
| spellingShingle | Di Cao Chunping Deng Guangying Wang Xiong Mei Jianhua Xie Yuanmei Liu Yujie Liu Yili Yang Shengfeng Li Cuihua Liu Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab Drugs in R&D |
| title | Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab |
| title_full | Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab |
| title_fullStr | Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab |
| title_full_unstemmed | Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab |
| title_short | Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab |
| title_sort | physicochemical and functional similarity assessment between proposed bevacizumab biosimilar bat1706 and reference bevacizumab |
| url | https://doi.org/10.1007/s40268-023-00432-8 |
| work_keys_str_mv | AT dicao physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT chunpingdeng physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT guangyingwang physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT xiongmei physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT jianhuaxie physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT yuanmeiliu physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT yujieliu physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT yiliyang physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT shengfengli physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab AT cuihualiu physicochemicalandfunctionalsimilarityassessmentbetweenproposedbevacizumabbiosimilarbat1706andreferencebevacizumab |