ICONIC-LEAD phase III trial Week 24 results: Icotrokinra in adults and adolescents with moderate-to-severe plaque psoriasis

Management of moderate-to-severe plaque psoriasis is often limited to injectable therapies. Icotrokinra (ICO) is a first-in-class, orally administered, targeted peptide that selectively binds to the interleukin-23 receptor and inhibits its downstream signaling.

ICO demonstrated significant skin clearance and a favorable safety profile in phase II trials, and is currently under evaluation in the phase III, randomized, double-blind, placebo-controlled ICONIC-LEAD trial (NCT06095115). 

At the EULAR 2025 Congress, Joseph Merola presented key findings from ICONIC-LEAD through Week 24, including clinical outcomes, patient-reported outcomes, and safety data. The co-primary endpoints were IGA 0/1 (clear [0]/almost-clear [1] skin and ≥2-grade improvement from baseline) and PASI 90 responses at Week 16. A total of 684 patients were randomized: 456 to the ICO group (mean age 42.4 years, 64% male) and 228 to the placebo group (mean age 43.2 years, 68% male).

Key learnings

At W16, the co-primary endpoints were met: 65% of ICO-treated vs 8% of placebo-treated patients achieved IGA 0/1, and 50% vs 4% achieved PASI 90 (both p < 0.001).

ICO demonstrated significant (all p < 0.0001) improvements vs placebo across clinical outcomes (IGA 0/1 [65% vs 8%]; PASI 90 [50% vs 4%]; PASI75 [69% vs 11%]; PASI 100 [27% vs <1%]; IGA 0 [33% vs 1%], ss-IGA 0/1 [72% vs 15%]), and PROs (PSSD itch [58% vs 13%]; PSSD Symptom 0 [20% vs 1%]) at W16, with benefits sustained through W24.

AEs at W16 were comparable between groups (49% each), with nasopharyngitis, URTI (7% each), and GI events (6%) being most common. No new safety concerns were identified through W24.

ICO resulted in significantly higher rates of clear or almost clear skin, improvement in scalp disease, and relief of PsO symptoms compared with placebo, along with a favorable safety profile in adults and adolescents with moderate-to-severe PsO.