Anti-MADCAM therapy for ulcerative colitis

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:

• Ulcerative colitis
• inflammatory bowel disease
• anti-MAdCAM
• ontamalimab
• SHP647

Article highlights

• Intestinal immune cell trafficking is emerging as an important factor in the pathogenesis of ulcerative colitis.

• Ontamalimab (SHP647) is a human IgG2 monoclonal antibody that binds to MAdCAM-1, preventing adhesion with integrins on lymphocytes, thereby reducing lymphocyte migration to the gut.

• Ontamalimab has demonstrated efficacy in Phase II clinical trials, with significant improvements in clinical remission, response, and mucosal healing.

• Phase III studies, evaluating the safety and efficacy of ontamalimab in ulcerative colitis are currently in progress.

This box summarizes the key points contained in the article.

Declaration of interest

S Picardo has received speaker fees from Pfizer, Takeda, and Janssen. R Panaccione has acted as a consultant for Abbvie, ActoGeniX, AGI Therapeutics, Alba Therapeutics Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Aptalis, Astellas, Athersys, Atlantic Healthcare, Biobalance, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek, Cellerix, Cerimon, ChemoCentryx, CoMentis, Cosdmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle, Eisai Medical Research, Elan, EnGene, Eli Lilly, Enteromedics, Exagen Diagnostics, Ferring, Flexion Therapeutics, Funxional Therapeutics, Genentech, Genzyme, Gilead, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood, Janssen, KaloBios, Lexicon, Lycera, Meda, Merck and Co., Merck Research Laboratories, MerckSerono, Millenium, Nisshin Kyorin, Novo Nordisk, NPS Pharmaceuticals, Optimer, Orexigen, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb, Purgenesis Technologies, Receptos, Relypsa, Salient, Salix, Santarus, Shire Pharmaceuticals, Sigmoid Pharma, Sirtris (a GSK company), S.L.A Pharma (UK), Targacept, Teva, Therakos, Tillotts, TxCell SA, UCB Pharma, Vascular Biogenics, Viamet and Warner Chilcott UK; has received speakers fees from Abbvie, Allergan, AstraZeneca, Ferring, Janssen, Merck, Prometheus, Pfizer, Shire and Takeda; is on an Advisory Board for Abbvie, Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Biogen Idec, Eisai, Ferring, Genentech, Janssen, Merch, Shire, Elan, Glaxo-Smith Kline, Hospira, Pfizer, Bristol-Myers-Squibb, Takeda, Cubist, Celgene, Salix; has received research/educational support from Abbvie, Ferring, Janssen, Shire and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.