About Etrolizumab

Specific Targets. Global Trial Program.

Proposed Mechanism of Action1-3

Etrolizumab is the first dual-action anti-integrin antibody in Phase III trials designed to selectively control disease in the gut of patients with Ulcerative Colitis (UC) and Crohn’s.

Activated white blood cells enter the gut mucosa when the α4β7 integrin on their surface bind to MAdCAM-1, a cell adhesion molecule found selectively on the surface of blood vessels in the gut mucosa. An excess of inflammatory cells builds up in the gut mucosa when the αEβ7 integrin on these cells binds to a cell adhesion molecule, E-cadherin, found in the gut mucosa.

This clinical trial program tests whether the proposed dual mechanism of action of etrolizumab prevents inflammatory cells from entering and being retained in the gut mucosa by specifically binding the β7 integrin subunit.

Proposed Dual MOA

DualMOA

 

The above image depicts the proposed mechanism of action (MOA) for etrolizumab. The exact MOA is unknown at this time. Etrolizumab is still being tested and has not been approved by any regulatory authorities, including the U.S. Food and Drug Administration (FDA). It is currently only available through clinical trials. The safety and effectiveness of etrolizumab are currently not known.

Patient Focused Studies

Etrolizumab investigational treatment in patients with UC resulted in full occupancy of β7 receptors on gut-homing lymphocytes in the peripheral blood and colonic tissue and coincident increases in gut-homing lymphocytes in the blood.

  • Administration of etrolizumab in group 1 (100 mg) and group 2 (420 mg loading dose followed by 300 mg) resulted in maximal occupancy of β7 receptors on β7+ gut-homing lymphocytes in the peripheral blood.
  • Etrolizumab treatment did not affect the numbers of non-intestinal homing β7− T-cells in peripheral blood of patients.
  • Administration of etrolizumab in group 1 (100 mg) and group 2 (420 mg loading dose followed by 300 mg) resulted in maximal occupancy of β7 receptors on β7-expressing T-cell subsets in colonic biopsies.

 

References:
1. Stefanich EG, et al. Br J Pharmacol. 2011;162:1855-70.
2. Rutgeerts PJ, et al. Gut. 2013;62:1122-30.
3. Vermeire S, et al. Lancet. 2014;384:309-18.

 

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