David Rubin, MD, reviews his presentation from the Advances in Inflammatory Bowel Diseases regional meeting on the newly-approved, first-in-class S1P receptor modulator, ozanimod, for treating ulcerative colitis.

David T. Rubin, MD, is the Joseph Kirsner Professor of medicine and chief of gastroenterology, hepatology, and nutrition at the University of Chicago.

TRANSCRIPT:

Dr. David Rubin:  Hi, I'm Dr. David Rubin. I'm a professor of medicine at the University of Chicago. At the Advances in IBD regional meeting, I gave a lecture on the new class of therapy we have in inflammatory bowel disease, the S1P receptor modulators.

Sphingosine 1-phosphates are signaling molecules that are related to how activated lymphocytes make their way through lymph ducts to find their way to areas of inflammation, injury, or infection.

The S1P receptor modulator therapies are targeted synthetic small molecules—that means they're oral— that modulate the transmembrane receptors of lymphocytes that enable them to follow the S1P signaling molecules to their targets.

When you modulate these receptors, you essentially make the activated white blood cells unable to leave lymph nodes and find their way, and then it down-regulates inflammation. We now have a first-in-class approved S1P receptor modulator for moderately to severely active ulcerative colitis. The therapy is called ozanimod, and it is an S1P1 and S1P5 inhibitor.

In my lecture, I go through the evidence supporting its efficacy and safety and I also talk about some other drugs within the class that are in development and other therapies that have already been studied and are available for multiple sclerosis.

The other therapy that I review in more detail is etrasimod, which is an S1P1, S1P4, and S1P5 receptor modulator. What we've learned about ozanimod is that it works quite rapidly to down-regulate inflammation. It was successful in its phase 3 trial called True North at achieving clinical remission and actually endoscopic response and an endpoint called mucosal healing, which included histologic response and remission as well, so obviously very effective.

S1Ps are present throughout our body. The different S1P types are present in different organ systems, or related to different physiologic processes. Because of this, what we've learned and what we need to do in understanding this therapy is that there may be some overlap in the cardiac conduction. So this isn’t a therapy we'd use in people who have type-2 heart block, which obviously is not common at all in our ulcerative colitis patients, and in which we would check an EKG to make sure we know their cardiac rhythm before we give the therapy.

We also want to make sure that if somebody has a history of uveitis, or diabetes, or other things that might affect the eyes, we make sure we work with an ophthalmologist. Now that may occur more commonly given that uveitis is an extraintestinal manifestation of IBD, and therefore, we'd want to make sure we understand whether we could use the therapy in that specific scenario.

We look for transient but important elevation of liver enzymes that we should know about. The usual targets and monitoring strategies we use for our different therapies across the field of IBD. Overall, this is an interesting class of therapy that offers a novel mechanism.

Ozanimod was approved without requiring that patients fail other therapies before they get it, so it might be positioned earlier in our management strategies.

I hope you have the time to learn more about this. If you can, please check out my lecture and learn the actual details of these data and how we might start using these therapies. Thank you very much.