Etrolizumab

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]

Etrolizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from rat)
Targetβ7 subunit of α4β7 and αEβ7 integrin heterodimers
Clinical data
ATC code
  • none
Identifiers
CAS Number
IUPHAR/BPS
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6396H9874N1702O2010S42
Molar mass144119.77 g·mol−1
 ☒NcheckY (what is this?)  (verify)

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 Feb 2022. [9]

References
  1. Adis Insight Etrolizumab 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".
  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. PMID 7523506. 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. Retrieved 2 January 2021.
  9. Fierce Biotech https://www.fiercebiotech.com/biotech/roche-lets-go-etro-dumping-phase-3-crohn-s-prospect-18-months-after-posting-weak-colitis. Retrieved 8 March 2023. {{cite web}}: Missing or empty |title= (help)


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