Etrolizumab (rhuMAb Beta7) is a biopharmaceutical drug candidate being developed for the treatment of ulcerative colitis and Crohn's disease. It is a humanized monoclonal antibody against the β7 subunit of integrins α4β7 and αEβ7.[1] Etrolizumab was developed by Genentech[2][3] by engineering the FIB504 antibody to include human IgGl-heavy chain and κ-light chain frameworks; it is manufactured in CHO cells.[4]
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from rat) |
| Target | β7 subunit of α4β7 and αEβ7 integrin heterodimers |
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| Chemical and physical data | |
| Formula | C6396H9874N1702O2010S42 |
| Molar mass | 144119.77 g·mol−1 |
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As of 2016, it was in phase III studies for induction and maintenance therapy in people with ulcerative colitis and Crohn's.[2][5][6] According to data of one meta-analysis efficacy of Etrolizumab is comparable with conventional therapies such as Infliximab with less adverse events.[7]
Phase III clinical trials produced mixed results; and, on October 14, 2020, Hoffmann-La Roche, the parent company of Genentech, abandoned further efforts to develop etrolizumab for ulcerative colitis, but continued development for Crohn's disease,[8] until disappointing trial results led to this being abandoned too in February 2022.[9]
References
edit- ^ Adis Insight Etrolizumab Archived 2016-06-03 at the Wayback Machine Latest Information Update: 16 Dec 2015
- ^ a b UK Medicines Information. etrolizumab at UKMI Archived 2016-06-04 at the Wayback Machine Page accessed May 10, 2016
- ^ "Genentech: Our Pipeline". www.gene.com. Archived from the original on 2020-05-24. Retrieved 2020-05-22.
- ^ WO 2012135589, "Methods of administering beta7 integrin antagonists", assigned to Genentech and Roche For the FIB504 mAb, see Andrew DP et al. Distinct but overlapping epitopes are involved in alpha 4 beta 7-mediated adhesion to vascular cell adhesion molecule-1, mucosal addressin-1, fibronectin, and lymphocyte aggregation. Andrew DP, Berlin C, Honda S, Yoshino T, Hamann A, Holzmann B, Kilshaw PJ, Butcher EC (November 1994). "Distinct but overlapping epitopes are involved in alpha 4 beta 7-mediated adhesion to vascular cell adhesion molecule-1, mucosal addressin-1, fibronectin, and lymphocyte aggregation". Journal of Immunology. 153 (9): 3847–61. doi:10.4049/jimmunol.153.9.3847. PMID 7523506. S2CID 32434092. as referenced in paragraph 146 of the PCT application.
- ^ Makker J, Hommes DW (2016). "Etrolizumab for ulcerative colitis: the new kid on the block?". Expert Opinion on Biological Therapy. 16 (4): 567–72. doi:10.1517/14712598.2016.1158807. PMID 26914639. S2CID 24706213.
- ^ Rosenfeld G, Parker CE, MacDonald JK, Bressler B (December 2015). "Etrolizumab for induction of remission in ulcerative colitis". The Cochrane Database of Systematic Reviews. 2015 (12): CD011661. doi:10.1002/14651858.CD011661.pub2. PMC 8612697. PMID 26630451.
- ^ Motaghi E, Ghasemi-Pirbaluti M, Zabihi M (January 2019). "Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis: A systematic review and indirect comparison". Pharmacological Research. 139: 120–125. doi:10.1016/j.phrs.2018.11.003. PMID 30395950. S2CID 53235342.
- ^ Tong, Amber (October 15, 2020). "Roche writes off ulcerative colitis portion of etrolizumab program, days after dissecting PhIII setback". Endpoints. Archived from the original on 24 November 2020. Retrieved 2 January 2021.
- ^ "Archived copy". Fierce Biotech. Archived from the original on 8 March 2023. Retrieved 8 March 2023.
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