Robust Icotrokinra Systemic and Skin Pharmacodynamic Effects Versus Deucravacitinib in Patients with Moderate-to-Severe Plaque Psoriasis: Results from Phase 3, Iconic-Advance-1 Study
Recommended Citation
Warren RB, Van den Heuvel AP, Li H, Chen E, Angsana J, Polak ME, Yum N, DeKlotz C, Sabins N, Stein Gold L, Gonzalez-Cantero A. Robust Icotrokinra Systemic and Skin Pharmacodynamic Effects Versus Deucravacitinib in Patients with Moderate-to-Severe Plaque Psoriasis: Results from Phase 3, Iconic-Advance-1 Study. J Am Acad Dermatol 2026; 95(1):AB393.
Document Type
Conference Proceeding
Publication Date
7-1-2026
Publication Title
J Am Acad Dermatol
Keywords
Dermatology
Abstract
Icotrokinra is a first-in-class targeted oral peptide that blocks IL-23R and inhibits IL-23 signaling. ICONIC-ADVANCE-1, a phase 3, placebo-controlled and deucravacitinib active comparator-controlled study, evaluated efficacy and safety of icotrokinra in participants with moderate-to-severe plaque psoriasis (PsO). Icotrokinra met co-primary endpoints of IGA 0/1 and PASI90 versus placebo at Week (W) 16; and met all key secondary endpoints demonstrating superiority over deucravacitinib.[1] Pharmacodynamic responses were assessed. Skin biopsies were collected (baseline and W16) in an optional sub-study (n=80) and analyzed via RNA-sequencing. Serum samples obtained at baseline and W24 from a substudy cohort (n=139) and healthy controls (n=22) were analyzed for proteins using Olink platform. Group comparisons between icotrokinra, deucravacitinib, and placebo were conducted using linear mixed-effect models. At W16, skin RNA-sequencing showed icotrokinra significantly reduced PsO-associated gene sets (Meta-Analysis Derived signatures in PsO)[2] and IL-23 pathway associated genes, such as IL17A, IL17F, IL22, IL19 and DEFB4A, compared to baseline (p<0.001); while placebo had no significant effect. Deucravacitinib also reduced expression of the PsO-associated gene sets, but at a lower magnitude compared to icotrokinra (p<0.05). Serum protein analyses at W24 similarly revealed significant reduction in IL-23 pathway and PsO-associated analytes (eg, IL-17A, IL-17C, BD-2 and IL-19) with icotrokinra (all p<0.0001), with at least 2-fold greater reductions compared with deucravacitinib (p<0.01). Icotrokinra significantly reduced systemic and skin PsO biomarkers to a greater extent than deucravacitinib. These pharmacodynamic findings align with the superior skin clearance achieved with icotrokinra, supporting its clinical efficacy through robust inhibition of IL-23 signaling and PsO disease activity.
Volume
95
Issue
1
First Page
AB393
