Dr Chiorean discusses his presentation at Digestive Disease Week on the promise of S1P modulators for the treatment of ulcerative colitis.

Michael Chiorean, MD, is codirector of the IBD Center at Swedish Medical Center in Seattle, Washington.

TRANSCRIPT

Michael Chiorean:  My name is Dr. Michael Chiorean. I'm a gastroenterologist at Swedish Medical Center in Seattle.

At the recent symposium which I presented at DDW, I discussed about new mechanisms of action that can be utilized or are upcoming in ulcerative colitis, specifically the advent of S1P receptor modulators.

The reason this important is because there is clearly still an unmet need as far as treatment options for patients with ulcerative colitis, as there is for patients with Crohn's disease. Certainly, biologics and small molecules have made a big difference in terms of treatment options and outcomes over the last 20 years, but there is still a substantial proportion of patients with UC who do not respond to these therapies and, as is the case with biologics, there is a substantial proportion of patients who will lose response to therapy over time.

So new mechanisms of action are always welcome, especially when they bring something novel, perhaps better efficacy, or efficacy in a niche portion of patients who have not responded to our other therapies, or a safety profile that is favorable.

That is the case with S1P receptor modulators. S1P stands for sphingosine 1-phosphate, which is an extracellular small molecular that works as a signaling molecule directing lymphocytes, specialized immune cells, to migrate within and outside lymph nodes, where this mechanism is more important, and during the traffic within lymph nodes, where lymphocytes use the S1P gradient as a guide to move from the periphery of the lymph node towards the efferent, or exit, from the lymph node, where they will then flow into the systemic circulation and reach the gut microcirculation. And from there, they join the inflammatory process in the intestine gas promoting and perpetuating inflammation.

S1P receptor modulators can blind the lymphocytes inside the lymph nodes and trap them inside the lymph nodes, thus preventing this positive feedback loop that essentially promotes the inflammation in the intestine. They can be considered lymph node trafficking inhibitors.

We now have several in the pipelines. One of them is in very advanced stages of development, specifically ozanimod. The phase 3 data was recently presented. I think this will provide a very good option for patients for several reasons. Again, it's an addition to the class of small molecules in a way. These are oral therapies that are very convenient in terms of patient preference, or the means of administration.

Also, the efficacy and safety profile is very favorable. Certainly, efficacy comparable to other advanced therapeutics, including biologic agents, and a safety profile that's also very good in terms of serious adverse events, such as serious infections and malignancy.

So I’m very excited to have a new therapeutic class in our armamentarium for ulcerative colitis for now, potentially for Crohn's disease in the future.