Investigational Oral IL-23 Receptor Antagonist Icotrokinra Improves Skin Clearance in Psoriasis in Phase 3 Study

Icotrokinra, a novel first-in-class oral peptide targeting the IL-23 receptor, significantly improved skin clearance in adults and adolescents with moderate-to-severe plaque psoriasis with no new safety signals identified. The findings, from the ICONIC-LEAD trial, were presented as a poster at the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference, July 23-26, 2025, in Las Vegas, Nevada.1

ICONIC-LEAD, led by Robert Bissonnette, MD, chairman of Innovaderm Research in Montreal, Canada, with an international team of investigators was a multicenter, randomized, double-blind, placebo-controlled phase 3 trial conducted at 170 sites worldwide. Bissonnette et al enrolled 684 participants aged 12 years or older with 10% or more body surface area (BSA) involvement, a Psoriasis Area and Severity Index (PASI) score of 12 or greater, and an Investigator’s Global Assessment (IGA) score 3 or greater.

The investigators randomized participants 2:1 to receive icotrokinra 200 mg once daily for 24 weeks (n=456) or placebo for 16 weeks followed by icotrokinra (n=228). ICONIC-LEAD coprimary endpoints, assessed at week 16, were the proportion of participants achieving PASI 90 and the proportion achieving an IGA score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline.

At the 16-week mark, significantly greater proportions of icotrokinra-treated participants achieved the study's endpoints compared to those receiving placebo:

• IGA 0/1: 65% vs 8%
• PASI 90: 50% vs 4%
• IGA 0: 33% vs 1%
• PASI 100: 27% vs <1%

(All comparisons multiplicity-adjusted P <.001)

Continued icotrokinra treatment through week 24 further increased response rates:

• IGA 0/1: 74%
• PASI 90: 65%
• IGA 0: 46%
• PASI 100: 40%

The adverse event (AE) rate was comparable between the treatment and placebo groups, according to the study, with 49% of participants in both arms reporting at least 1 AE during the study's first 16 weeks. Nasopharyngitis and upper respiratory tract infections were the most common AEs. Gastrointestinal events occurred in 6% of participants in each group. The investigators reported no new safety concerns through week 24.

Bissonnette and colleagues concluded that oral icotrokinra significantly improves skin clearance in adults and adolescents with moderate-to-severe psoriasis and maintains a safety profile comparable to placebo over 24 weeks.

Johnson and Johnson is developing icotrokinra and on July 21 submitted a new drug application to the FDA seeking first approval of the IL-23 inhibitor in the US.

References

1. Bissonnette R, Soung J, Lebwohl M, et al. Icotrokinra, a targeted oral pepetiede that selectively blcoks the interleukin-21 receptor, for the treatment of moderate-to-severe plaque psoriasis: results through week 24 of the phase 3, randomized, double-blind, placebo-controlled ICONIC-LEAD Trial. Poster presented at DERM 2025 NP PA CME Conference; July 23-26, 2025; Las Vegas, Nevada.

2. Johnson & Johnson seeks first icotrokinra US FDA approval aiming to revolutionize treatment paradigm for adults and adolescents with plaque psoriasis. News release. Johnson and Johnson. July 21, 2025. Accessed August 11, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-first-icotrokinra-u-s-fda-approval-aiming-to-revolutionize-treatment-paradigm-for-adults-and-adolescents-with-plaque-psoriasis