ANTHEM-UC: Icotrokinra Shows Sustained Efficacy in Moderate-to-Severe Ulcerative Colitis, With Vipul Jairath, MBChB, DPhil

When treated with Johnson and Johnson’s icotrokinra, adults with moderate to severe ulcerative colitis (UC) experienced dose-dependent improvements in clinical and endoscopic outcomes with a durable response, and favorable safety in the phase 2b ANTHEM-UC study’s patient population.1

The findings were presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting by Vipul Jairath, MBChB, DPhil, MRCP1, a professor of medicine, epidemiology, and biostatistics at Western University, and reported on the safety and efficacy findings for 3 doses of icotrokinra.

Investigational icotrokinra is a first-in-class targeted oral peptide designed to selectively block IL-23 receptor activation, with the potential to modulate or inhibit the inflammatory response in moderate-to-severe plaque psoriasis, ulcerative colitis, and other IL-23 mediated diseases. The drug is being investigated in the ongoing phase 3 ICONIC clinical development program.2

“Icotrokinra has a novel mechanism of action. It’s a pill and it’s a peptide, so it can be taken orally. It’s also highly potent for the IL-23 receptor, and I think that’s the key differentiating factor,” said Jairath in an interview in HCPLive. “It has low oral bioavailability, but very high potency for the IL-23 receptor itself. So it blocks the receptor, the site of action, and its subunits, and in doing so, it blocks the downstream inflammatory cytokines mediated through the IL-23 pathway.”

The results presented at ACG come from a 28-week follow-up of ANTHEM-UC, a phase 2b, randomized, double-blind, placebo-controlled, treat-through, dose-ranging study. In adults with moderate to severe UC, participants were randomly assigned in a 1:1:1:1 ratio to once-daily oral icotrokinra 100 mg, 200 mg, 400 mg, or placebo. At week 16, any patient meeting inadequate response criteria had a treatment adjustment where patients in placebo switched to icotrokinra 400 mg, while icotrokinra patients had a sham adjustment.

Investigators noted a week 12 primary endpoint of clinical response and week 28 exploratory endpoints of clinical response, clinical remission, symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI).

Among the 252 randomized participants, the mean modified Mayo score (mMS) was 6.63, with 31.9% having mMS >7 and 58.7% presenting with a Mayo endoscopy subscore (MES) of 3, indicating moderate to severe disease activity. Nearly half (43.3%) were biologic, JAK inhibitor, or sphingosine-1-phosphate receptor modulator inadequate responders (BIO/JAKi/S1P-IR). Patients were stratified by prior biologic, JAKi, or S1P receptor modulator inadequate response status (BIO/JAKi/S1P-IR; yes or no [Y/N]) and by MES 2 or 3.

By week 16, inadequate response criteria were met by 38.1% of placebo-treated patients (n = 24) compared with 17.2%, 17.7%, and 11.1% of those receiving icotrokinra 100 mg (n = 11), 200 mg (n = 11), and 400 mg (n = 7), respectively.

At week 28, all icotrokinra doses demonstrated clinically meaningful improvements versus placebo in clinical response, clinical and symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI), with response rates increasing from week 12 through week 28.

Per each dose group, adverse events occurred in 61.9%, 65.6%, 66.1%, and 60.3% of patients. Serious adverse events and discontinuations were 11.1%, 0%, 6.5%, and 3.2%. No serious infections, malignancies, hepatic events, venous thromboembolism, major cardiovascular events, or deaths were reported in the patient population treated with icotrokinra.

“I think what you see clearly with that is some incremental benefit with continued treatment and persistence of response, said Jairath. “There's been no new safety concerns that would be expected from this class of action. I think most importantly, we haven't seen any areas of specialist interest. No cardiovascular events, no thrombosis, no tuberculosis.”

Editor’s Note: Jairath reports relevant disclosures with AbbVie, Alimentiv, Arena, and others.

References:

1. Jairaith, V, Siegmund, B, Surace, L, et al. Efficacy and Safety of Icotrokinra, a Targeted Oral Peptide That Selectively Blocks IL-23 Receptor Activation, in Ulcerative Colitis: Results From Week 28 of ANTHEM-UC, a Phase 2b Dose-Ranging Trial Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

2. Icotrokinra long-term results affirm promise of targeted oral peptide with high rates of durable skin clearance and favorable safety profile in difficult-to-treat scalp and genital psoriasis. Jnj.com. Published 2023. Accessed November 12, 2025. https://www.investor.jnj.com/investor-news/news-details/2025/Icotrokinra-long-term-results-affirm-promise-of-targeted-oral-peptide-with-high-rates-of-durable-skin-clearance-and-favorable-safety-profile-in-difficult-to-treat-scalp-and-genital-psoriasis/default.aspx