New therapies for inflammatory bowel disease

2016-06-11
John Marshall

What new therapies for inflammatory bowel disease (IBD) can we expect in the near future?

John Marshall: We are in a very good era for development of new therapies both for Crohn disease and ulcerative colitis. In fact I have to tell my newly diagnosed patients that there has never been a better time to have either of these disorders.

Already in the last few years we have seen new therapies appear, for example, biologic therapies. We have seen development of a new class of biologics. We have had the anti-tumor necrosis factor (TNF) therapies, now we have a new class to target leukocyte trafficking, related to how white blood cells are delivered to the intestinal compartment to incite and sustain the inflammation in Crohn disease. Vedolizumab is the first agent which has become commercially available for treatment of IBD that targets the alpha-4-beta-7 integrin. Previously we had a monoclonal antibody against the alpha-4 integrin, but there were some safety issues because it was not specific to the gut. But in the near future we will also have monoclonal antibody targeting the beta-7 integrin, which has some very specific potential advantage over the alpha-4-beta-7 blockade. We also have a monoclonal antibody in development targeting the other side of that interaction, which is mucosal addressin cell adhesion molecule (MAdCAM), to which the alpha-4-beta-7 integrin binds. So that is blocking the same interaction at the other side and that antibody is in development as well. Just recently, in the last few months, we have had news about the efficacy of ustekinumab, which is a monoclonal antibody that blocks both interleukin (IL) 12 and IL-23, and that has shown strong efficacy in Crohn disease and is already on the market for psoriasis. Those data are new and just later this month the Digestive Disease Week (DDW) 2016 will see data on maintenance with that agent.

But behind that there is a whole host of therapies in late-stage development that could appear in the next few years. One, for example, is tofacitinib, an oral janus kinase inhibitor – cause the holy grail in IBD drug development is to find treatment that is orally administered, efficacious, and well-tolerated. So we have several oral therapies in late-stage development. Tofacitinib for ulcerative colitis might be the first to receive approval in the world. But then behind that we also have apremilast, another oral therapy for ulcerative colitis, and of course we have mongersen, an oral antisense oligonucleotide against SMAD7, which is in phase 3 trials now for treatment of Crohn disease, with very strong phase 2 data showing a high therapeutic gain over placebo with very early response. That agent has generated a lot of excitement and it remains to be seen whether that strong signal is confirming in phase 3 trials. To see all these encouraging oral therapies on the horizon is very good, so I do not doubt that in the next 5 years our toolbox is going to be a lot bigger.

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