Dr Jairath discusses the phase 2B study results of icotrokinra, a novel, oral interleukin-23 peptide, for the treatment of moderately to severely active ulcerative colitis, which were presented at the ACG 2025 Scientific Meeting.

Vipul Jairath, MBChB, is Professor of Medicine, Epidemiology, and Biostatistics and director of the Advanced IBD fellowship at Western University in London, Ontario, Canada.

TRANSCRIPT:

My name is Vipul Jairath. I'm a gastroenterologist and professor of medicine at Western University in London, Ontario, Canada. I was part of the steering committee for the ANTHEM UC trial, which was presented at this meeting. And I'm going to summarize the results.

So we know the IL 23 pathway is very important in the pathogenesis of inflammatory bowel disease, both in ulcerative colitis and Crohn's disease. And IL 23s have been well established now in clinical practice. And there's 3 IL-23 inhibitors now approved. ANTHEM UC was a phase 2B dose ranging study of icotrokinra in patients with moderate to severely active ulcerative colitis. And I think the very novel aspect of this compound is, first it's an oral therapy and second, a peptide. And thirdly, it blocks the IL 23 receptor directly.

So the drug is orally administered once a day, and it has a very high potency for the IL 23 receptor. It has very low systemic bioavailability, less than 1%, but high potency for the receptor. And in this trial, patients were randomized in an equal ratio to 1 of 3 doses of icotrokinra or placebo. So it was 400 milligrams daily, 200 milligrams daily, 100 milligrams daily or placebo. And the primary endpoint was at week 12 for clinical response.

We presented those top line data just 2 or 3 weeks ago at the UEGW Congress and we saw a very clear dose response relationship versus placebo for each dose of icotrokinra and for the highest dose, almost touching a 40% delta of the placebo for clinical response.

The data that we presented this meeting with a continued data out to week 28, and what we saw for the primary endpoint of clinical response was some evidence of continued incremental benefit over time with treatment and also persistence. And this was also seen consistently for most of the secondary endpoints as well. Those include clinical remission, endoscopic remission, and the combined endpoint of endoscopic and histological remission. There were no unexpected safety signals seen in this trial, and specifically there were no adverse events of specialist interest, specifically no VTS thrombosis, MACE, or cardiovascular events. Based upon the results of these trials, the compound will now progress into phase 3 trials, which are being planned at this time.