ICOTYDE - Treatment of Ulcerative Colitis (ANTHEM-UC)

SUMMARY

• The company cannot recommend any practices, procedures, or usage of ICOTYDE (icotrokinra) that deviate from the approved labeling.
• ANTHEM-UC (NCT06049017) is an ongoing phase 2b clinical trial evaluating the efficacy and safety of icotrokinra 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 icotrokinra on systemic and tissue biomarkers of inflammatory burden.¹
• Results through week 28 of the phase 2b, randomized, double-blind, placebo (PBO)-controlled, treat-through dose-ranging study are reported below.^2-6
• Results from the long-term extension (LTE) are summarized below.⁷

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 either^2,3:
  • Icotrokinra 100 mg by mouth (PO) once daily
  • Icotrokinra 200 mg PO once daily
  • Icotrokinra 400 mg PO once daily
  • PBO
• 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 icotrokinra 400 mg and PBO 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:
  • PBO patients were switched to icotrokinra 400 mg PO once daily.
  • Icotrokinra 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 icotrokinra on systemic and tissue inflammation.⁵

Results

• Overall, 252 patients were randomized. The mean age and UC duration were 41.6 years and 7.8 years, respectively. At baseline, 37.3% of patients were receiving concomitant corticosteroids and 43.3% had a history of IR to ADT.²
• At week 16, 38.1% of patients were nonresponders.³

Efficacy

• At week 12, icotrokinra 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.

• Compared to PBO, all icotrokinra 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 icotrokinra group.³ See Table: Week 28 Endpoints vs PBO.

Subgroup Analyses at Week 12

Loftus et al (2026)⁴ evaluated the efficacy of icotrokinra through week 28 in patients with moderately to severely active UC, including subpopulations with and without prior inadequate or intolerance to advanced therapies (ADT-IR).

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 icotrokinra 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 1 ADT class. In the PBO group, 78.6% (n=22) of patients had exposure to 1 ADT class.
  • A total of 23.1% (n=6), 19.2% (n=5), and 48.3% (n=14) of patients treated with icotrokinra 100 mg, 200 mg, and 400 mg had exposure to 2 ADT classes, respectively. Notably, 1 patient (3.8%) in the icotrokinra 100 mg group had exposure to more than 2 ADT classes. In the PBO group, 21.4% (n=6) had exposure to 2 ADT classes.
• At week 12, clinically meaningful efficacy was observed with icotrokinra vs PBO across 5 endpoints in ADT-IR and non-ADT-IR populations; results are summarized in Figures: Efficacy of icotrokinra at Week 12 in Non-ADT-IR Subpopulation and Efficacy of icotrokinra at Week 12 in ADT-IR Subpopulation.

Safety

• Through week 12, no opportunistic infections, tuberculosis, malignancies, clinically important hepatic disorders, major adverse cardiovascular events (MACEs), or deaths were reported in icotrokinra groups.²
• Similar proportions of adverse events (AEs) and serious AEs were reported among patients receiving PBO and icotrokinra. 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 icotrokinra.³

Additional Analyses

Inflammatory Biomarkers

• Clinical inflammatory biomarkers including CRP, FCP, IL-22, IL-17A, and IL-17F were assessed to evaluate the effects of icotrokinra on inflammation. Changes in gene expression within colonic biopsy samples were analyzed to confirm these findings.
• At week 12, all icotrokinra doses reduced CRP and FCP levels. In addition, all icotrokinra doses, but not PBO, 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 icotrokinra on Clinical Inflammatory Biomarkers and Serum Levels of IL-23 Pathway Cytokines in Patients with UC.⁵
• At week 12, all icotrokinra doses, but not PBO, reduced the expression of gene sets associated with IL-23-driven inflammation compared to baseline. See Figure: Impact of icotrokinra on Tissue Expression of IL-23 Pathway Genes in Patients with UC.⁵
• With icotrokinra, 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

Exploratory Endoscopic and Histologic Endpoints

• Histologic improvement, histologic remission, endoscopic remission, and the composite of histologic remission and clinical remission were additional exploratory endpoints and were assessed at weeks 12 and 28.⁶
• At week 12, greater proportions of patients receiving all icotrokinra doses vs those receiving PBO were in endoscopic remission, histologic remission, histologic improvement, and histologic remission and clinical remission.⁶
• For endoscopic and histologic endpoints at weeks 12 and 28, see Figures: Exploratory Endoscopic and Histologic Endpoints at Week 12 and Exploratory Endoscopic and Histologic Endpoints at Week 28.

LTE Analyses

Study Population and Design

• Patients achieving clinical response at week 28 could enter the LTE.⁷
• In the LTE, dose adjustment or initiation of 5-ASA, corticosteroids, and immunomodulators were permitted.
• After week 28 analyses were complete, the treatment was unblinded, and patients receiving PBO were discontinued from the study.
• At week 76, clinical response, clinical remission, and endoscopic improvement were evaluated with nonresponder imputation (NRI) applied. Endpoints using the Mayo score were determined using local endoscopy subscores.
• The final safety evaluation was performed at week 78.

Results

• Of 136 patients who entered the LTE, the majority were in clinical response, clinical remission, and endoscopic improvement at week 76.⁷
• The rates of symptomatic remission were maintained through week 76, see Figure: Symptomatic Improvement through Week 76.

• For efficacy outcomes at week 76, see Table: Efficacy Endpoints at Week 76.

• Of the patients included in the LTE analysis, 87% remained on treatment through week 78.⁷
• No new safety signals were identified.
• Through week 78 (full analysis set), rates of AEs, serious adverse events (SAEs), AEs leading to discontinuation, and infections per 100 patient-years (PY) were similar or lower with icotrokinra compared with PBO.
• In the icotrokinra 100 mg group, 1 AE of interest (in situ ductal carcinoma) was reported during the LTE; no deaths were reported.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 03 September 2026.