Etrolizumab

Etrolizumab

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from rat)
Target	β7 subunit of α4β7 and αEβ7 integrin heterodimers
Clinical data
ATC code	none
Identifiers
CAS Number	1044758-60-2^N
IUPHAR/BPS	8407
ChemSpider	none
UNII	I2A72G2V3J
KEGG	D09901^N
Chemical and physical data
Formula	C6396H9874N1702O2010S42
Molar mass	144119.77 g·mol^−1
^NY (what is this?)  (verify)

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]

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

1. Adis Insight Etrolizumab Archived 2016-06-03 at the Wayback Machine Latest Information Update: 16 Dec 2015
2. UK Medicines Information. etrolizumab at UKMI Archived 2016-06-04 at the Wayback Machine Page accessed May 10, 2016
3. "Genentech: Our Pipeline". www.gene.com. Archived from the original on 2020-05-24. Retrieved 2020-05-22.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. "Archived copy". Fierce Biotech. Archived from the original on 8 March 2023. Retrieved 8 March 2023.