Icotrokinra ulcerative colitis tablet roughly doubles week 12 response in a phase 2 trial

A phase 2 trial of icotrokinra ulcerative colitis treatment reports that the oral peptide produced a clinical response at week 12 in more than half of patients, against about a quarter on placebo. The study randomised 252 adults with moderately to severely active disease to one of three daily tablet strengths or a dummy tablet. Results appeared in the New England Journal of Medicine in October 2026, with Maria Abreu of Cedars Sinai in Los Angeles as first author. Johnson and Johnson, which develops the drug, funded the work.

What icotrokinra is and why a tablet matters

Icotrokinra is an oral peptide built to block the interleukin 23 receptor, the docking point for a signalling protein that sustains part of the chronic inflammation in the gut lining. Antibodies acting on the same pathway are already used for inflammatory bowel disease, but they are given by infusion or injection because digestion breaks down large proteins. Icotrokinra is far smaller and was engineered to survive long enough to work as a once daily tablet. Current antibodies grab the signalling protein, while this peptide sits on the receptor and stops the signal from landing, Abreu told a gastroenterology meeting this month, according to Healio. The drug is not new to regulators. The FDA approved it in March 2026 under the brand name Icotyde for moderate to severe plaque psoriasis.

For ulcerative colitis it remains investigational, and the study reported here is the step that decides whether larger trials make sense. People with this disease often cycle through steroids, immune suppressants and injected biologics, and many lose their response over time. An oral drug aimed at a validated pathway would change the routine of care, since no infusion chair or injection training would be needed, and the investigators stress that convenience. The trial cannot yet say whether a tablet works as well as the injected antibodies that share its target, because it never compared them. It measured the peptide only against placebo, which is the usual design at this stage but leaves the most practical question for patients and doctors open. Background on why so few peptides survive the gut is in our explainer on peptide pills.

Week 12 results of the icotrokinra ulcerative colitis trial

Adults entered the ANTHEM UC trial with moderately to severely active disease on the modified Mayo scale and visible inflammation at endoscopy. Many had already failed conventional drugs or advanced therapies such as biologics, according to the paper and a conference account in Healio. Participants were split almost evenly across four arms of 62 to 64 people and took one tablet a day without knowing which arm they were in. The main measure was clinical response at week 12, a composite that combines stool frequency, rectal bleeding and the endoscopic picture. Clinical remission, a stricter bar, came next along with symptomatic remission and endoscopic improvement. These secondary measures were tested in a fixed order starting with the highest strength, and formal testing stopped once a comparison failed.

All three tablet strengths beat placebo on the main measure, with response rates of 55 to 63 percent against 27 percent.

All three tablet strengths beat placebo on the main measure, with response rates of 55 to 63 percent against 27 percent. The gap was widest at the highest strength. On the stricter measures the highest strength again separated from placebo: clinical remission reached 30 percent against 11 percent, symptomatic remission 46 percent against 19 percent, and endoscopic improvement 37 percent against 14 percent. The middle strength reached 24 percent remission, which fell short of statistical significance, and under the prespecified order that ended the formal secondary analysis. That detail matters for anyone reading the paper closely. Several comparisons involving the two smaller strengths are descriptive only, so apparent differences between them should not be treated as established, and the best dose for later trials is still an open choice.

Side effects and the longer follow up

Through week 28, adverse events of any kind were reported by 60 to 66 percent of people on icotrokinra and by 62 percent on placebo, so the overall rate did not rise with the drug. Serious adverse events were uncommon in every arm and were most frequent on placebo, at 10 percent, against 0 to 5 percent on the active tablets. One plausible reading is that uncontrolled colitis itself leads to hospital stays, which the drug arms partly avoided, but the trial was not designed to test that idea. The arms were also small. With about 63 people in each, one or two events move a percentage by several points, and rare harms of a new drug usually surface only in larger and longer studies.

The trial continued into a long term extension that ran to week 76, presented at the American College of Gastroenterology meeting in Nashville. Healio reported that 136 patients entered that phase, that most kept their response, and that 97 percent of those in clinical remission at week 76 were free of corticosteroids. Those figures come from people who stayed on treatment and chose to continue, which tends to flatter any drug, since patients who did badly have often left by then. Abreu also noted that people who had never received an advanced therapy did better than those who had. That pattern is common in bowel disease research, and if it holds in larger studies it would point toward using the tablet earlier in the course of the illness.

What a phase 2 trial cannot show

A phase 2 trial of 252 people is built to choose doses and decide whether a bigger programme is justified, not to establish how well a drug works in everyday care. The uncertainty around each response rate is wide, and the main comparison came after only twelve weeks. There was no active comparator, so nothing yet shows how the tablet stacks up against injected interleukin 23 antibodies or other oral drugs used in colitis. The study also cannot speak to people with mild disease or to children. Because Johnson and Johnson funded the work and the first author reports consulting for several companies including the sponsor, independent phase 3 data will carry more weight for the icotrokinra ulcerative colitis programme than this first result.

For readers following peptide drugs in people, the result shows that oral delivery is no longer limited to the gut hormone class. Icotrokinra joins a short list of peptides engineered to survive digestion, and its psoriasis approval shows that regulators accept the approach when the trial data hold up. Whether the same tablet can earn a colitis label depends on larger trials that must confirm the response rates, follow safety over years and enrol a more varied group of patients. Until then the drug is approved only for psoriasis, and use in bowel disease outside a study would be off label. The trial is registered as NCT06049017, and patients curious about the research should raise it with their own gastroenterologist rather than act on a single paper.

Conclusion

The icotrokinra ulcerative colitis trial gives a clear but early signal. A once daily peptide tablet roughly doubled the week 12 response rate against placebo in adults with moderate to severe disease, without a rise in overall side effects. The study was small, sponsor funded and short, and it compared the drug only with a dummy tablet. Larger trials will decide whether a medicine already approved for psoriasis earns a second use in the gut.

Source Abreu MT and colleagues. Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis. The New England Journal of Medicine, October 2026. DOI 10.1056/NEJMoa2604435. ClinicalTrials.gov NCT06049017

Amino Weekly reports research. It is not medical advice and never gives doses.