0875: Efficacy and Safety of Icotrokinra, a Novel Targeted Oral Peptide (IL-23R-Inhibitor), in Adolescents With Moderate-to-Severe Plaque Psoriasis: Subgroup Analyses From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (ICONIC-LEAD)

Background/Purpose: Icotrokinra (ICO), a novel targeted oral peptide, binds the interleukin (IL)-23 receptor to inhibit IL-23 signaling. ICONIC-LEAD (NCT06095115) is the first Phase 3 study in moderate-to-severe psoriasis to assess the efficacy and safety of a systemic therapy simultaneously in adolescents and adults.

Methods: In ICONIC-LEAD, adolescents (12 to < 18 years) with moderate-to-severe psoriasis (body surface area [BSA] ≥10%, Psoriasis Area and Severity Index [PASI] ≥12, Investigator’s Global Assessment [IGA] ≥3) and body weight ≥40 kg were randomized 2:1 to once-daily ICO 200 mg or placebo through Week 16. Placebo patients transitioned to ICO after Week 16. Overall ICONIC-LEAD co-primary endpoints, IGA 0/1 response (IGA score=cleared [0] or minimal [1] and ≥2-grade improvement) and PASI 90 response at Week 16, were assessed in adolescents, as were the efficacy and safety through Week 24.

Results: Adolescents comprised 9.6% (66/684) of the ICONIC-LEAD population. The mean age was 15 years and the mean psoriasis disease duration was 5.2 years (Table). Higher proportions of adolescents receiving ICO vs placebo achieved clear/almost clear skin at Week 16 (IGA 0/1: 84.1% vs 27.3%; PASI 90: 70.5% vs 13.6%; nominal p< 0.001). At Week 24, rates of clear/almost clear skin with ICO were 86.4% (IGA 0/1) and 88.6% (PASI 90; Figure). Response patterns were consistent for IGA 0 and PASI 100. At Week 16, 50% of ICO and 73% of placebo adolescents had ≥1 adverse event; no safety signals emerged through Week 24.

Conclusion: In adolescents with moderate-to-severe psoriasis, higher proportions of ICO vs placebo participants achieved clear/almost clear skin at Week 16, with unprecedented response rates at Week 24 and a favorable adverse event profile.