Anti-MADCAM therapy for ulcerative colitis

Expert Opin Biol Ther. 2020 Apr;20(4):437-442. doi: 10.1080/14712598.2020.1691520. Epub 2019 Nov 13.

Abstract

Introduction: The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) plays a key role in the endothelial adhesion and migration of lymphocytes to sites of inflammation in inflammatory bowel disease. Therapies that target this pathway appear to be a promising therapeutic approach in the management of ulcerative colitis (UC).Areas covered: This review provides a summary of the preclinical and available clinical data on the safety and efficacy of ontamalimab (SHP647), a fully human monoclonal antibody that binds and inhibits the action of MAdCAM-1.Expert opinion: Intestinal immune cell trafficking is emerging as an important component in the pathogenesis of UC. Ontamalimab (SHP647) inhibits this process by preventing the binding of integrins found on the surface of lymphocytes and the endothelial ligand adhesion molecule MAdCAM-1. This monoclonal antibody has already demonstrated safety and efficacy in phase II clinical trials. Its targeted mechanism of action suggests a superior safety profile as compared with the current systemic immunosuppressive therapies. Results from the phase III trials are awaited to establish ontamalimab (SHP647) as a therapeutic option in the management of UC.

Keywords: SHP647; Ulcerative colitis; anti-MAdCAM; inflammatory bowel disease; ontamalimab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Clinical Trials as Topic
  • Colitis, Ulcerative / drug therapy*
  • Endothelial Cells / metabolism
  • Headache / etiology
  • Humans
  • Mucoproteins / immunology*
  • Mucoproteins / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Cell Adhesion Molecules
  • MADCAM1 protein, human
  • Mucoproteins
  • ontamalimab