Icotrokinra an oral IL-23 Receptor Blocker Shows Sustained Efficacy in Ulcerative Colitis: NEJM

To determine the efficacy and safety of oral icotrokinra, a randomized, placebo-controlled trial at Phase 2b was performed among 252 adults who had moderately to severely active ulcerative colitis. Subjects were divided randomly into four parallel groups wherein they were given once daily dose of 400 mg oral icotrokinra (n=63), 200 mg oral icotrokinra (n=62), 100 mg oral icotrokinra (n=64), or placebo (n=63).

The primary end point is the proportion of subjects who had a clinical response by week 12. Secondary end points measured at week 12 include clinical remission, symptomatic remission, and mucosal endoscopic improvement. End points related to safety and adverse events are monitored among all subjects receiving the drug up to week 28.

Key findings:

• Evaluation among the 252 subjects who participated in the trial showed dose-dependent superiority over placebo along with safety profiles up to week 28.
• The three oral doses of icotrokinra were statistically significantly superior to placebo regarding clinical response at week 12, which occurred in 63% for the 400-mg dose, 58% for the 200-mg dose, 55% for the 100-mg dose, compared to 27% for the placebo group (P < 0.001 for all comparisons).
• For the 400-mg dose group, there was statistical significance in clinical remission at week 12 (30% vs. 11%, P = 0.006), symptomatic remission (46% vs. 19%, P < 0.001), and endoscopic improvement (37% vs. 14%, P = 0.002).
• For the 200-mg dose group, clinical remission occurred in 24% (P = 0.054 vs. placebo group), and according to fixed-sequence testing, there was no need for any further formal secondary tests in lower dose groups.
• Adverse events occurred in 60% of the 400-mg dose group, 66% of the 200-mg dose group, 66% of the 100-mg dose group, and 62% of the placebo group during week 28.
• The percentage of serious adverse events was 2%, 5%, 0%, and 10%, respectively.

The results from the Phase 2b trial have demonstrated that once daily oral administration of icotrokinra has elicited a significant clinical response, symptom remission, and endoscopic response in patients suffering from active ulcerative colitis. The conclusions drawn from this trial have underscored the fact that oral icotrokinra is an extremely efficacious and well-tolerated targeted therapy modality.

Reference:

Abreu, M. T., Siegmund, B., Surace, L., Erondu, N., Chen, M., Chachu, K., Louis, E., Matsuoka, K., Limdi, J., Arthur, E., Houck, N., Marano, C., Vetter, M. L., Zou, B., Zhan, J., Frustaci, M. E., Kannan, A. K., Rydzewska, G., Loftus, E. V., & Jairath, V. (2026). Phase 2 trial of icotrokinra for patients with ulcerative colitis. New England Journal of Medicine, 395(15), 1495–1504. https://doi.org/10.1056/nejmoa2604435