ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0558

Early Systemic and Skin Pharmacodynamic Effects of Icotrokinra in Participants with Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3, ICONIC-LEAD Study

Julianty Angsana1, Marta Polak1, Sharan Nischal1, Elizabeth Chen1, Deepika Balakrishna2, Ching-Heng Chou1, Christopher Sisk3, Lynn Tomsho1, Arun Kannan1, Cynthia DeKlotz1, Megan Miller4, Joseph Cafone3, Paul Newbold1, Ya-Wen Yang1, Monica Leung1, Dawn Waterworth1, Nina Sabins1, Anna Perillo5, Andreas Pinter6 and Robert Bissonnette7, 1Johnson & Johnson, San Diego, CA, USA, San Diego, CA, 2Johnson & Johnson, San Diego, CA, USA, San Diego, USA, 3Johnson & Johnson, San Diego, CA, USA, San Diego, CA, CA, 4Johnson & Johnson, San Diego, CA, USA, San Diego, CA,, CA, 5The Rockefeller University, New York, NY, USA, New York, NY, 6Goethe University Frankfurt, Frankfurt, Germany, Frankfurt, Germany, 7Innovaderm Research, Montreal, QC, Canada, Montreal, QC

Meeting: ACR Convergence 2025

Keywords: , , ,

Session Information

Date: Sunday, October 26, 2025

Title: (0554–0592) Spondyloarthritis Including Psoriatic Arthritis – Treatment Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Icotrokinra (ICO), a first-in-class targeted oral peptide that blocks the interleukin (IL)-23R and inhibits IL-23 pathway signaling, is being evaluated in the phase 3 ICONIC-LEAD study in participants ≥12 years with moderate-to-severe plaque psoriasis (PsO). Study co-primary endpoints were met, with ICO demonstrating significantly higher Investigator’s Global Assessment (IGA) 0/1 (64.7% vs 8.3%) and Psoriasis Area and Severity Index (PASI) 90 (49.6% vs 4.4%) response rates vs placebo at Week (W) 16 (both p < 0.001). ICO pharmacodynamics were assessed via serum protein and skin transcriptomic analyses.

Methods: Participants (N&#3f684) were randomized 2:1 to once-daily ICO 200 mg or placebo through W16. After W16, placebo participants transitioned to ICO (placebo®ICO). Serum collected at W0, W4, and W16 from a sub-cohort (n=166 for IL-22; n=167 for other analytes) and a distinct healthy control cohort (n=30; BioIVT, Hicksville, NY) was analyzed to determine soluble IL-17A, IL-17F, IL-19, IL-22, and BD-2 concentrations. Skin biopsies collected at W0 and W24 from consenting participants of an optional sub-study (n=65) were analyzed for mRNA expression. Comparisons between ICO and placebo used linear mixed-effect modeling that included effects for W0 levels, treatment-over-time interaction, and participant random effect.

Results: Serum IL-17A, IL-17F, IL-19, IL-22, and BD-2 levels were significantly higher in participants with PsO at baseline (W0) vs healthy control (p < 0.05). ICO significantly reduced serum biomarker levels vs placebo (all p < 0.05 at W4 and W16) and relative to W0 levels as early as W4 (p < 0.0001 for all analytes). Serum biomarker concentrations continued to decrease in participants receiving ICO, with levels at W16 (all p < 0.0001 vs W0) approaching those of healthy control. At W0, 1026 genes were significantly upregulated and 970 significantly downregulated (adjusted p < 0.05) in lesional vs non-lesional skin. At W24, ICO significantly reduced PsO-related gene set enrichment (MAD-3, MAD-5) and gene expression, including IL17A, IL17F, IL22, IL19, IL23A, and DEFB4A (all p < 0.0001 vs W0 lesional) to levels approaching those seen in W0 non-lesional skin. Similar significant reductions were observed after 8 weeks of ICO treatment in the placebo®ICO cohort (all p < 0.0001 vs W0 lesional).

Conclusion: Consistent with its mechanism of action of selectively and potently blocking the IL-23R, ICO significantly attenuated systemic and skin biomarkers related to IL-23 pathway activation and PsO disease severity. Findings demonstrated both early and substantial ICO effects, with levels of IL-23 pathway biomarkers of systemic and skin inflammation normalizing to a healthy state. Overall, these comprehensive biomarker findings are consistent with significant skin clearance achieved with this first targeted oral peptide to selectively inhibit IL-23 pathway activation.

Disclosures: J. Angsana: Johnson & Johnson, 3, 11; M. Polak: Johnson & Johnson, 3, 11; S. Nischal: Johnson & Johnson, 3, 11; E. Chen: Johnson & Johnson, 3, 11; D. Balakrishna: Johnson & Johnson, 3, 11; C. Chou: Johnson & Johnson, 3, 11; C. Sisk: Johnson & Johnson, 3, 11; L. Tomsho: Johnson & Johnson, 3, 11; A. Kannan: Johnson & Johnson, 3, 11; C. DeKlotz: Johnson & Johnson, 3, 11; M. Miller: Johnson & Johnson, 3, 11; J. Cafone: Johnson & Johnson, 3, 11; P. Newbold: Johnson & Johnson, 3, 11; Y. Yang: Johnson & Johnson, 3, 11; M. Leung: Johnson & Johnson, 3, 11; D. Waterworth: Johnson & Johnson, 3, 11; N. Sabins: Johnson & Johnson, 3, 11; A. Perillo: AbbVie, 2, 5, 6, Allergan, 2, 6, Almirall, 2, 6, Amgen, 2, 5, 6, Aristea, 2, 6, Artax Biopharma, 2, 5, 6, Avillion, 5, Biogen Idec, 2, 5, 6, Boehringer-Ingelheim, 2, 5, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Bruxelles Biopharma, 5, Calliditas, 2, 6, Eli Lilly, 2, 5, 6, Escalier, 2, 6, Exicure, 5, Immunotherapeutics, 2, 6, Incyte, 2, 5, 6, Innovaderm, 5, Janssen, 2, 5, 6, Kymera Therapeutics, 2, 6, Kyowa Kirin, 2, 5, 6, MC2 Therapeutics, 2, 6, Merck, 2, 6, MoonLake, 2, 6, Novan, 5, Novartis, 2, 5, 6, Nuvig Therapeutics, 2, 6, ONO-Pharma, 5, Oruka Therapeutics, 2, 6, Pfizer, 2, 5, 6, Provectus, 5, Regeneron, 5, Sanofi, 2, 6, SUDO Bio, 5, Sun Pharma, 2, 6, Takeda, 2, 5, 6, Target-Derm, 2, 6, UCB, 2, 5, 6, UNION Therapeutics, 2, 6, Valeant, 2, 6, Ventyx, 2, 6, Vitae Pharmaceuticals, 5; A. Pinter: AbbVie, 1, 5, 6, Almirall, 1, 5, 6, Amgen, 1, 5, 6, Biogen Idec, 1, 5, 6, BioNTech, 1, 5, 6, Boehringer Ingelheim, 1, 5, 6, Celgene, 1, 5, 6, Celltrion, 1, 5, 6, Eli Lilly, 1, 5, 6, Galderma, 1, 5, 6, GlaxoSmithKlein(GSK), 1, 5, 6, GmbH, 1, 5, 6, Hexal, 1, 5, 6, Johnson & Johnson, 1, 5, 6, Klinge Pharma, 1, 5, 6, LEO Pharma, 1, 5, 6, MC2 Therapeutics, 1, 5, 6, Medac, 1, 5, 6, Merck, 1, 5, 6, Mitsubishi, 1, 5, 6, MSD, 1, 5, 6, Novartis, 1, 5, 6, Pascoe, 1, 5, 6, Pfizer, 1, 5, 6, Regeneron, 1, 5, 6, Roche, 1, 5, 6, Sandoz Biopharmaceuticals, 1, 5, 6, Sanofi Genzyme, 1, 5, 6, Schering-Plough, 1, 5, 6, Tigercat Pharma, 1, 5, 6, UCB Pharma, 1, 5, 6, Zuellig Pharma, 1, 5, 6; R. Bissonnette: AbbVie, 2, 5, Amgen, 2, 5, Apogee, 2, Arcutis, 2, 5, Asana, 2, Bellus, 5, BioMimetix, 5, Bluefin, 2, Boehringer-Ingelheim, 2, Boston Pharma, 2, Cara Therapeutics, 5, Clexio, 5, Dermavant, 2, 5, Eli Lilly, 2, Escient, 2, 5, Evidera, 2, Fresh Tracks, 5, Galderma, 2, GlaxoSmithKline, 2, Incyte, 2, 5, Innovaderm, 11, Janssen, 2, 5, LEO Pharma, 2, 5, Merck, 5, Novartis, 2, Opsidio, 5, Pfizer, 2, 5, RAPT Therapeutics, 2, Sanofi Genzyme, 2, Sanofi-Aventis, 2, Target RWE, 2, 5, Vyne Therapeutics, 5, Xencor, 5.

To cite this abstract in AMA style:

Angsana J, Polak M, Nischal S, Chen E, Balakrishna D, Chou C, Sisk C, Tomsho L, Kannan A, DeKlotz C, Miller M, Cafone J, Newbold P, Yang Y, Leung M, Waterworth D, Sabins N, Perillo A, Pinter A, Bissonnette R. Early Systemic and Skin Pharmacodynamic Effects of Icotrokinra in Participants with Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3, ICONIC-LEAD Study [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/early-systemic-and-skin-pharmacodynamic-effects-of-icotrokinra-in-participants-with-moderate-to-severe-plaque-psoriasis-results-through-week-24-of-the-phase-3-iconic-lead-study/. Accessed .

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