ICONIC-ADVANCE: Icotrokinra Beats Deucravacitinib for Plaque Psoriasis

Icotrokinra, Johnson & Johnson’s first-in-class investigational targeted oral IL-23 inhibitor, was superior to deucravacitinib (Sotyktu) for achieving skin clearance at weeks 16 and 24 in patients with moderate-to-severe plaque psoriasis.

Announced on September 17, 2025, the data, which suggest icotrokinra also demonstrated similar adverse event rates to placebo are further supported by 52-week data from the ICONIC-LEAD study. Both of these were presented at the European Association of Dermatology and Venereology (EADV) 2025 Congress.

“These head-to-head data clearly demonstrate superior complete skin clearance rates for icotrokinra compared to deucravacitinib,” said Linda Stein Gold, MD, director of Dermatology Clinical Research at Henry Ford Health and ICONIC-ADVANCE study investigator.1 “With significantly higher response rates seen as early as Week 16 and increasing at Week 24, this novel targeted oral peptide treatment has the potential to be an appealing new option for patients with moderate-to-severe plaque psoriasis.”

Icotrokinra has captured the attention of dermatologists and healthcare providers throughout 2025 as a flurry of data releases and announcements of intent to file regulatory submissions have many waiting with bated breath for further phase 3 data beyond the 16-week results of the phase 3 ICONIC-LEAD trial.1,2

ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 were phase 3 trials designed to assess the efficacy and safety of icotrokinra against both placebo therapy and deucravacitinib in adults with moderate-to-severe plaque psoriasis. The trials enrolled more than 1500 adult patients1

The trials had coprimary endpoints of the percentage of participants achieving an Investigator's Global Assessment (IGA) score of 0 or 1 and greater than or equal to a 2-grade improvement from baseline at week 16 as well as the percentage of participants achieving Psoriasis Area and Severity Index (PASI) 90 response at week 16.1

In their September 17, 2025 announcement, Johnson & Johnson disclosed icotrokinra met both co-primary endpoints compared to placebo at week 16 with similar adverse event rates and showed superiority to deucravacitinib for skin clearance at weeks 16 and 24. The release also pointed out no new safety signals were identified in the trial, with event rates numerically lower with icotrokinra relative to deucravacitinib through 24 weeks.1

“We’re excited to see the icotrokinra Phase 3 ICONIC program continue to deliver robust and clinically meaningful head-to-head and long-term results,” said Liza O’Dowd, MD, vice president of Immunodermatology and Respiratory Disease Areas Lead at Johnson & Johnson Innovative Medicine.1 “A novel oral therapy that can provide complete skin clearance, a favorable safety profile and the simplicity of a once daily pill may offer an important new option that could increase the use of systemic treatments among patients with moderate-to-severe plaque psoriasis.”

ICONIC-LEAD, which had its 16-week primary endpoint data presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting, was once again a topic of conversation. In the original study, results indicated 65% of patients treated with icotrokinra achieved an IGA score of 0 or 1 at 16 weeks, compared to 8% of the placebo group (P <.001).2

New data from the EADV 2025 Congress showed PASI 90 responders re-randomized to icotrokinra at week 24 had superior maintenance of a PASI 90 response compared to those re-randomized to placebo in week 52 results (84% vs 21%; P <.001). Additionally, 86% of adolescents who received icotrokinra for the full 52 weeks and 77% of those switched from placebo to icotrokinra at week 16 achieved PASI 90 response at 52 weeks.1

“With a substantial proportion of adults and adolescents achieving clear or almost clear skin while maintaining a favorable safety profile through 52 weeks, icotrokinra could be a compelling new therapeutic option that aligns with both patient and provider goals for an oral treatment once approved,” said study investigator Jennifer Soung, MD, director of Clinical Research at Southern California Dermatology.1

References:

1. Johnson & Johnson. Icotrokinra shows superiority to deucravacitinib in first reported head-to-head trials reinforcing promise of novel targeted oral peptide for treatment of plaque psoriasis. JNJ.com. Published September 17, 2025. Accessed September 17, 2025. https://www.jnj.com/media-center/press-releases/icotrokinra-shows-superiority-to-deucravacitinib-in-first-reported-head-to-head-trials-reinforcing-promise-of-novel-targeted-oral-peptide-for-treatment-of-plaque-psoriasis

2. Bissonnette R. Icotrokinra, a Targeted Oral Peptide That Selectively Blocks the Interleukin-23–Receptor, for the Treatment of Moderate-to-Severe Plaque Psoriasis. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.