S1449 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

Introduction: As previously reported, all 3 doses of icotrokinra (ICO; JNJ-2113)—a first-in-class targeted oral peptide that selectively blocks IL-23 receptor activation — met the week (W) 12 primary endpoint in ANTHEM-UC, a Phase 2b, randomized, double-blind, placebo-controlled, treat-through, dose-ranging study in adults with moderate to severe ulcerative colitis (UC). Here we report W28 efficacy and safety of ICO from ANTHEM-UC. Methods: Participants (pts) had a modified Mayo score (mMS) of 5–9 inclusive, a Mayo endoscopy subscore (MES) ≥2, and inadequate response/intolerance (IR) to TNFα blockers, vedolizumab, ustekinumab, JAK inhibitors, or S1P receptor modulators (BIO/JAKi/S1P-IR) or IR to corticosteroids, AZA, or 6-MP. Randomization (1:1:1:1) to once-daily (once a day) oral ICO 100 mg, 200 mg, 400 mg or placebo (PBO) was stratified by BIO/JAKi/S1P-IR status (Y/N) and MES (2 or 3). Clinical response at week 12 was the primary endpoint. Clinical response, clinical remission, symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI) were further evaluated at week 28 as exploratory endpoints. Pts meeting inadequate response criteria at week 16 had a treatment adjustment: PBO pts switched to ICO 400 mg once a day and ICO pts had a sham adjustment. All pts meeting inadequate response criteria were considered non-responders moving forward. Results: Analyses included all 252 randomized pts who received study medication: mean mMS, 6.63; mMS >7, 31.9%; MES = 3, 58.7%; BIO/JAKi/S1P-IR, 43.3%. Week 16 inadequate response criteria were met by 24 (38.1%), 11 (17.2%), 11 (17.7%) and 7 (11.1%) pts receiving PBO & ICO 100, 200 and 400 mg. Relative to PBO, all ICO doses demonstrated clinically meaningful rates of clinical response, clinical remission, symptomatic remission, endoscopic improvement, and 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 ICO dose group. Through week 28, ≥1 AE (61.9%, 65.6%, 66.1%, 60.3%), SAEs (9.5%, 0%, 4.8%, 1.6%), or AEs leading to discontinuation of study agent (11.1%, 0%, 6.5%, 3.2%) were reported in pts in the PBO & ICO 100, 200 and 400 mg groups. No serious or opportunistic infections, tuberculosis, malignancies, clinically important hepatic disorders, VTE, MACE, or deaths were reported with ICO. Conclusion: In ANTHEM-UC, clinical efficacy and a favorable safety profile were observed with once-daily ICO through week 28 in pts with moderate to severe UC.