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ICOTYDE - Treatment of Ulcerative Colitis (ANTHEM-UC)
Last Updated: 05/20/2026
SUMMARY
- The company cannot recommend any practices, procedures, or usage of ICOTYDE that deviate from the approved labeling.
- ANTHEM-UC (NCT06049017) is an ongoing phase 2b clinical trial evaluating the efficacy and safety of ICOTYDE in adult patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response (IR) or intolerance to advanced or conventional therapy and assessing the impact of ICOTYDE on systemic and tissue biomarkers of inflammatory burden.1
- Results through week 28 of the phase 2b, randomized, double-blind, placebo-controlled, treat-through dose-ranging study are reported below.2
- 5
CLINICAL DATA
ANTHEM-UC Phase 2b Dose-Ranging Study
Study Population and Design
- Adults with a modified Mayo Score (mMS) of 5-9 and a Mayo endoscopic subscore (MES) of ≥2.2,
3 - History of IR/intolerance to advanced therapy (ADT; tumor necrosis factor [TNF]-alpha inhibitors, vedolizumab, ustekinumab, Janus kinase [JAK] inhibitors, sphingosine type-1 receptor modulators [S1PRMs]) or conventional therapy (corticosteroids, azathioprine [AZA], mercaptopurine [MP]).2,3
- Patients were stratified by MES 2 or 3 and by history of IR to ADT (yes or no) and randomized 1:1:1:1 to either2,3:
- ICOTYDE 100 mg by mouth (PO) once daily
- ICOTYDE 200 mg PO once daily
- ICOTYDE 400 mg PO once daily
- Placebo
- Primary endpoint: clinical response at week 12 (decrease in the mMS by ≥30% and ≥2 points, with either a ≥1-point decrease in rectal bleeding from baseline or a rectal bleeding score [RBS] of 0 or 1).2,3
- The study was powered to detect a treatment difference between ICOTYDE 400 mg and placebo for the primary endpoint; it was not powered for the secondary or exploratory endpoints.2
- Patients meeting IR criteria at week 16 underwent treatment adjustment3:
- Placebo patients were switched to ICOTYDE 400 mg PO once daily.
- ICOTYDE patients had a sham adjustment.
- All patients meeting IR criteria were considered nonresponders moving forward.3
- Systemic biomarkers (clinical biomarkers, including C-reactive protein [CRP] and fecal calprotectin [FCP], and serum interleukin [IL]-23 pathway biomarkers, including IL-22, IL-17A, and IL-17F) and tissue biomarkers (gene expression changes in colonic biopsy) were evaluated to determine the impact of ICOTYDE on systemic and tissue inflammation.5
Results
Efficacy
- At week 12, ICOTYDE met the primary endpoint at doses of 100 mg, 200 mg, and 400 mg once daily.2 For details, see Table: Week 12 Endpoints vs PBO.
| ICOTYDE 400 mg Once Daily N=63 | ICOTYDE 200 mg Once Daily N=62 | ICOTYDE 100 mg Once Daily N=64 | PBO N=63 | |
|---|---|---|---|---|
| Primary endpoint, % | ||||
| Clinical response | 63.5 P<0.001 | 58.1 P<0.001 | 54.7 P<0.001 | 27.0 |
| Secondary endpoints, % | ||||
| Clinical remissiona | 30.2 P=0.006 | 24.2 P=0.054 | 21.9 P=0.092 | 11.1 |
| Symptomatic remissionb | 46.0 P<0.001 | 41.9 Nominal P-valuec | 53.1 Nominal P-valuec | 19.0 |
| Endoscopic improvementd | 36.5 P=0.002 | 33.9 Nominal P-valuec | 26.6 P=0.072 | 14.3 |
| HEMIe | 28.6 Nominal P-valuec | 25.8 Nominal P-valuec | 15.6 P=0.419 | 11.1 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; MES, Mayo endoscopic subscore; PBO, placebo. aClinical remission was defined as stool frequency subscore of 0 or 1, rectal bleeding score of 0, and MES of 0 or 1. bSymptomatic remission was defined as a stool frequency subscore of 0 or 1 and a rectal bleeding score of 0. cNominal P-value for ICOTYDE vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established. dEndoscopic improvement was defined as MES of 0 or 1. eHEMI was defined as histologic remission (absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement (MES of 0 or 1). | ||||
- Compared to placebo, all ICOTYDE doses demonstrated clinically meaningful rates of clinical response, clinical remission, symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI) at week 28.
- Relative to week 12 outcomes, rates of clinical response, clinical remission, endoscopic improvement, and HEMI continued to increase through week 28 in each ICOTYDE group.3 See Table: Week 28 Endpoints vs PBO.
| PBO N=63 | ICOTYDE 400 mg Once Daily N=63 | ICOTYDE 200 mg Once Daily N=62 | ICOTYDE 100 mg Once Daily N=64 | |
|---|---|---|---|---|
| Endpoints, % | ||||
| Clinical response | 25.4 | 66.7 Nominal P-valuec | 62.9 Nominal P-valuec | 60.9 Nominal P-valuec |
| Clinical remissiona | 9.5 | 31.7 Nominal P-valuec | 33.9 Nominal P-valuec | 40.6 Nominal P-valuec |
| Symptomatic remissionb | 20.6 | 52.4 Nominal P-valuec | 53.2 Nominal P-valuec | 51.6 Nominal P-valuec |
| Endoscopic improvementd | 11.1 | 38.1 Nominal P-valuec | 38.7 Nominal P-valuec | 50.0 Nominal P-valuec |
| HEMIe | 11.1 | 33.3 Nominal P-valuec | 30.6 Nominal P-valuec | 40.6 Nominal P-valuec |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; MES, Mayo endoscopic subscore; PBO, placebo. aClinical remission was defined as stool frequency subscore of 0 or 1, rectal bleeding score of 0, and MES of 0 or 1. bSymptomatic remission was defined as a stool frequency subscore of 0 or 1 and a rectal bleeding score of 0. cNominal P-value for ICOTYDE vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established. dEndoscopic improvement was defined as MES of 0 or 1. eHEMI was defined as histologic remission (absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement (MES of 0 or 1). | ||||
Subgroup Analyses at Week 12
Loftus et al (2026)4
Results
- Of 252 patients, 143 (56.7%) and 109 (43.3%) patients were randomized into the
non- ADT-IR and ADT-IR subpopulations, respectively. - Among the ADT-IR subpopulation, exposure to prior ADT classes varied across treatment groups.
- In the ICOTYDE 100 mg, 200 mg, and 400 mg groups, 73.1% (n=19), 80.8% (n=21), and 51.7% (n=15) of patients, respectively, had exposure to one ADT class. In the PBO group, 78.6% (n=22) of patients had exposure to one ADT class.
- A total of 23.1% (n=6), 19.2% (n=5), and 48.3% (n=14) of patients treated with ICOTYDE 100 mg, 200 mg, and 400 mg had exposure to two ADT classes, respectively. Notably, one patient (3.8%) in the ICOTYDE 100 mg group had exposure to more than two ADT classes. In the PBO group, 21.4% (n=6) had exposure to two ADT classes.
- At week 12, clinically meaningful efficacy was observed with ICOTYDE vs placebo across 5 endpoints in ADT-IR and non-ADT-IR populations; results are summarized in Figures: Efficacy of ICOTYDE at Week 12 in Non-ADT-IR Subpopulation and Efficacy of ICOTYDE at Week 12 in ADT-IR Subpopulation.
Abbreviations: ADT, advanced therapy; CI, confidence interval; HEMI, histologic-endoscopic mucosal improvement; ICO, icotrokinra; IR, inadequate response; PBO, placebo.
Clinical response: A decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1
Symptomatic remission: Stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0
Clinical remission: Stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and Mayo endoscopic subscore of 0 or 1
Endoscopic improvement: Mayo endoscopic subscore of 0 or 1
Histologic–endoscopic mucosal improvement: Histologic remission (absence of neutrophils from the mucosa in both lamina propria and epithelium, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement (Mayo endoscopic subscore of 0 or 1).
Abbreviations: ADT, advanced therapy; CI, confidence interval; HEMI, histologic-endoscopic mucosal improvement; ICO, icotrokinra; IR, inadequate response; PBO, placebo.
Clinical response: A decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1
Symptomatic remission: Stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0
Clinical remission: Stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and Mayo endoscopic subscore of 0 or 1
Endoscopic improvement: Mayo endoscopic subscore of 0 or 1
Histologic–endoscopic mucosal improvement: Histologic remission (absence of neutrophils from the mucosa in both lamina propria and epithelium, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement (Mayo endoscopic subscore of 0 or 1.
Participants with intercurrent events of ostomy or colectomy, prohibited changes in UC medication, or discontinuation of study intervention for any reason except those due to major disruptions (e.g., COVID-19– related reasons or regional crisis, excluding COVID-19 infection) were considered non-responders. For participants discontinuing study intervention due to major disruptions, their observed values, if available, were used. After accounting for these scenarios, participants who were missing data necessary for calculation of the outcome measure at the assessment timepoint were considered not to have achieved that endpoint.
Safety
- Through week 12, no opportunistic infections, tuberculosis, malignancies, clinically important hepatic disorders, major adverse cardiovascular events (MACEs), or deaths were reported in ICOTYDE groups.2
- Similar proportions of adverse events and serious adverse events were reported among patients receiving placebo and ICOTYDE. See Table: Safety through Week 28.3
- Through week 28, no serious or opportunistic infections, tuberculosis, malignancies, clinically important hepatic disorders, venous thromboembolism (VTE), MACEs, or deaths were reported with ICOTYDE.3
| PBO N=63 | ICOTYDE 100 mg Once Daily N=64 | ICOTYDE 200 mg Once Daily N=62 | ICOTYDE 400 mg Once Daily N=63 | |
|---|---|---|---|---|
| ≥1 AEs, % | 61.9 | 65.6 | 66.1 | 60.3 |
| SAEs, % | 9.5 | 0 | 4.8 | 1.6 |
| AEs leading to discontinuation of study agent, % | 11.1 | 0 | 6.5 | 3.2 |
| Abbreviations: AE, adverse event; PBO, placebo; SAE, serious adverse event. | ||||
Additional Analyses
Inflammatory Biomarkers
- Clinical inflammatory biomarkers including C-reactive protein (CRP), fecal calprotectin (FCP), IL-22, IL-17A, and IL-17F were assessed to evaluate the effects of ICOTYDE on inflammation. Changes in gene expression within colonic biopsy samples were analyzed to confirm these findings.
- At week 12, all ICOTYDE doses reduced CRP and FCP levels. In addition, all ICOTYDE doses, but not placebo, reduced serum IL-22, IL-17A, and IL-17F levels compared to baseline, with greater reductions observed with the 200 mg and 400 mg doses compared with the 100 mg dose. See Figure: Impact of ICOTYDE on Clinical Inflammatory Biomarkers and Serum Levels of IL-23 Pathway Cytokines in Patients with UC.5
- At week 12, all ICOTYDE doses, but not placebo, reduced the expression of gene sets associated with IL-23-driven inflammation compared to baseline. See Figure: Impact of ICOTYDE on Tissue Expression of IL-23 Pathway Genes in Patients with UC.5
- With ICOTYDE, tissue transcriptome more closely resembled healthy individuals, with decreased expression of gene sets associated with UC and increased expression of genes characteristics of healthy epithelial cells.
- Through week 28, reductions in systemic and tissue inflammation were sustained.5
Note: *, **, *** = nominal P-value for log2 fold change from baseline. Nominal P-value for icotrokinra vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established. Track mean values or estimated marginal means were plotted using a linear mixed effect model that accounted for treatment*time interaction, age, and sex, with subject as random effect. Error bars are model-based standard errors.
Abbreviations: CRP, C-reactive protein; FCP, fecal calprotectin; ICO, icotrokinra; IL, interleukin; PBO, placebo.
Quantification of IL-23 pathway gene enrichment score using GSVA at the indicated time points after PBO or ICO treatment.
GSVA scores are depicted and compared at week 0 and week 12, or week 28 with a t-test.
Note: *** = nominal P-value. Nominal P-value for icotrokinra vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established. Error bars are 95% CI.
Abbreviations: CI, confidence interval; GSVA, gene set variation analysis; ICO, icotrokinra; IL, interleukin; PBO, placebo.
Literature Search
A literature search of MEDLINE®
References
| 1 | Janssen Research & Development, LLC. A study of JNJ-77242113 in participants with moderately to severely active ulcerative colitis (ANTHEM-UC). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 February 13]. Available from: https://clinicaltrials.gov/study/NCT06049017 NLM Identifier: NCT06049017. |
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