Johnson & Johnson announced positive Week 12 results from the Phase 2b ANTHEM-UC study of icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis. The study met its primary endpoint, with all once-daily icotrokinra dose groups achieving clinical response at Week 12 and showing clinically meaningful improvements versus placebo across key secondary endpoints.
Dose-Dependent Clinical Response
At Week 12, patients treated with 400 mg of icotrokinra once-daily achieved a clinical response rate of 63.5% versus 27% for placebo (p<0.001), while patients treated with 200 mg and 100 mg of icotrokinra once-daily achieved 58.1% and 54.7% response rates, respectively. Clinical response was defined as a decrease from baseline in the modified Mayo score by greater than or equal to 30% and greater than or equal to 2 points, with either a greater than or equal to 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
Secondary Endpoint Achievements
Across multiple secondary endpoints, the 400 mg icotrokinra group demonstrated significantly greater proportions of patients achieving clinical remission (30.2% vs 11.1% placebo, p=0.006), symptomatic remission (46.0% vs 19% placebo, p<0.001), and endoscopic improvement (36.5% vs 14.3% placebo, p=0.002) at Week 12 compared to placebo. Both the 200 mg and 100 mg once-daily dosing groups also showed meaningful improvements in these secondary endpoints relative to placebo.
All icotrokinra doses demonstrated higher rates of symptomatic remission compared to placebo as early as Week 4, indicating rapid onset of therapeutic benefit.
Safety Profile
Similar proportions of participants reported adverse events and serious adverse events through Week 12 across all icotrokinra dose groups and the placebo group, suggesting a favorable safety profile for the investigational therapy.
"Ulcerative colitis can bring unpredictable and often debilitating symptoms that make even simple daily activities a challenge for many patients," said Maria T. Abreu, M.D., Executive Director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai in Los Angeles and study investigator. "The ANTHEM-UC study results highlight how icotrokinra can selectively target the IL-23 pathway and address the underlying inflammation using a once-daily, oral therapy that is easy for patients, while offering therapeutic benefit and a favorable safety profile."
Advancing to Phase 3 Development
Based on results from the Phase 2b ANTHEM-UC study, Johnson & Johnson has initiated the ICONIC-UC Phase 3 protocol in adults and adolescents with moderately to severely active UC as well as the ICONIC-CD Phase 2b/3 protocol in adults with moderately to severely active Crohn's disease. Icotrokinra is also being studied in the pivotal Phase 3 ICONIC program in moderate-to-severe plaque psoriasis and the ICONIC-PSA 1 and ICONIC-PSA 2 studies in active psoriatic arthritis.
A New Drug Application (NDA) was submitted to the U.S. Food and Drug Administration (FDA) in July 2025 seeking the first approval of icotrokinra for the treatment of adults and pediatric patients 12 years of age and older with moderate to severe plaque psoriasis.
Novel Mechanism of Action
Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque psoriasis, ulcerative colitis and offers potential in other IL-23-mediated diseases. Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signalling in human T cells.
"Icotrokinra marks the next chapter in our history of innovation in inflammatory bowel disease, building on our deep scientific expertise in the IL-23 pathway to develop targeted solutions that address the complexity of disease biology and meet the real-world needs of patients," said Esi Lamousé-Smith, M.D., Ph.D., Vice President, Gastroenterology Disease Area Lead, Immunology, Johnson & Johnson.
Study Design and Patient Population
ANTHEM-UC (NCT06049017) is a Phase 2b multicenter, randomized, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of icotrokinra in patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics (TNF antagonists or vedolizumab) and/or ozanimod or approved JAK inhibitors. The study evaluated three once-daily dosages of icotrokinra taken orally.
The license and collaboration agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company, in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra. Johnson & Johnson retains exclusive worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.
