|
Synonyms: PRO145223 | RG-7413 | RG7413 | rhuMAb Beta7
Compound class:
Antibody
Comment: Etrolizumab is a humanized monoclonal antibody targeting integrin receptors containing the ITGB7 (β7) subunit (namely α4β7 and αEβ7).
Peptide sequence information for this antibody is available from its IMGT/mAb-DB record. Peptide sequence matches indicate that US7528236 is the covering patent [4]. The likely candidate antibody clone is that designated hu504.32R. Etrolizumab has a slightly different mechanism of action compared to the already approved ulcerative colitis biologic vedolizumab (Entyvio®), which targets only α4β7 integrin. 
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| No information available. |
Summary of Clinical Use  |
| Etrolizumab was progressed to Phase 3 clinical trials as a potential treatment for Crohn's disease and ulcerative colitis (UC) [11]. All four of the UC trials have completed (as of August 2020), with mixed and somewhat dissapointing results, although nothing has yet been published (see Fierce Biotech summary here). At this time etrolizumab trials in Crohn's are still proceeding. |
| Mechanism Of Action and Pharmacodynamic Effects |
| The targeted intergrin receptors appear to play a role in inflammatory bowel diseases, by modulating lymphocyte numbers entering the gut [1,5-6]. Gut-selective blockade of lymphocyte trafficking is being pursued as a potential treatment for inflammatory bowel dieases [2-3,10] in an attempt to improve upon the non-selective nature of currently used therapies such as azathioprine, mercaptopurine, infliximab, adalimumab and golimumab. Etrolizumab antagonises the interaction of α4β7 integrin receptors with their ligand, MAdCAM-1. This action inhibits the migration of lymphocytes from the mucosal vasculature into the gatrointestinal lumen. In addition, antibody-induced inhibition of binding between αEβ7 receptors and E-cadherin increases lymphocyte retention within the intraepithelial compartment [7-8]. The overall effect is to selectively reduce the numbers of lymphocytes, and hence the inflammatory response in the gut of patients with ulcerative colitis or Crohn's disease. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT02163759 | A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors (Study #1) | Phase 3 Interventional | Hoffmann-La Roche | HIBISCUS I induction study- in people without prior anti-TNF treatment. | |
| NCT02171429 | A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors (Study #2) | Phase 3 Interventional | Hoffmann-La Roche | HIBISCUS II induction study- in anti-TNF treatment naive patients | |
| NCT02100696 | A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors | Phase 3 Interventional | Hoffmann-La Roche | HICKORY study- in patients with prior anti-TNF treatment experience | |
| NCT02165215 | A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors | Phase 3 Interventional | Hoffmann-La Roche | LAUREL maintenance study- in patients without prior anti-TNF treatment | |
