Icotrokinra Outperforms Deucravacitinib in Psoriasis Phase 3 Trials

At the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Johnson & Johnson presented pivotal phase 3 data on icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the interleukin-23 (IL-23) receptor. Results from the ICONIC-ADVANCE 1 and 2 trials confirmed superiority over deucravacitinib, an approved oral TYK2 inhibitor, while new 1-year findings from the ICONIC-LEAD study demonstrated sustained efficacy and favorable safety in adults and adolescents with moderate-to-severe plaque psoriasis.^1,2

ICONIC-ADVANCE: Superiority Over Deucravacitinib

The ICONIC-ADVANCE studies compared icotrokinra with placebo and deucravacitinib in adult patients. According to the study, icotrokinra met both co-primary endpoints versus placebo at week 16, achieving significantly higher rates of skin clearance while maintaining similar adverse event rates. Importantly, icotrokinra demonstrated superiority to deucravacitinib at multiple timepoints, including weeks 16 and 24, with numerically lower adverse event rates through 24 weeks.

“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, in a press release. “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.”

ICONIC-LEAD: One-Year Durability in Adults and Adolescents

Long-term outcomes from the ICONIC-LEAD withdrawal and re-treatment trial reinforced icotrokinra’s durable efficacy. At week 52, among adult PASI 90 responders at week 24, 84% who continued icotrokinra maintained their PASI 90 response, compared with just 21% of those re-randomized to placebo (p<0.001).

In adolescents, continuous therapy led to robust outcomes, with 86% achieving PASI 90 at week 52. Even among those initially randomized to placebo and switched to icotrokinra at week 16, 77% achieved PASI 90 by the end of the year. These results highlight the drug’s consistent efficacy across age groups.

“The long-term data from ICONIC-LEAD continue to demonstrate the potential of icotrokinra to address the need for a novel targeted oral psoriasis treatment,” said Jennifer Soung, MD, director of clinical research at Southern California Dermatology and ICONIC-LEAD investigator. “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.”

ICONIC-ASCEND: Expanding into Biologic Comparisons

Johnson & Johnson has also initiated the ICONIC-ASCEND study, the first phase 3 trial designed to compare an oral psoriasis therapy directly with an injectable biologic. The study will evaluate the superiority of icotrokinra against ustekinumab, an IL-12/23 inhibitor. If successful, ICONIC-ASCEND could establish oral therapies as a viable alternative to injectable biologics in moderate to severe psoriasis management.

Safety Profile

Across both ICONIC-ADVANCE and ICONIC-LEAD, icotrokinra maintained a favorable safety profile. Adverse event rates were similar to placebo and numerically lower than those observed with deucravacitinib, with no new safety signals identified through 52 weeks.

Future Outlook

“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, immunodermatology and respiratory disease areas lead, Johnson & Johnson Innovative Medicine, in the release. “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.”

Conclusion

The ICONIC program’s results position icotrokinra as a promising oral therapy capable of rivaling or surpassing existing options. By demonstrating superiority to deucravacitinib, sustained efficacy through 1 year, and tolerability across age groups, icotrokinra could offer a transformative addition to the psoriasis treatment landscape. With the ICONIC-ASCEND trial now underway, further insights will determine whether an oral IL-23 inhibitor can directly challenge injectable biologics in clinical practice.

References

1. Icotrokinra shows superiority to deucravacitinib in first reported head-to-head trials reinforcing promise of novel targeted oral peptide for treatment of plaque psoriasis. Press release. Johnson & Johnson. 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. Soung J. Maintenance of response with icotrokinra, a targeted oral peptide, for the treatment of moderate to severe plaque psoriasis: randomized treatment withdrawl in adults (weeks 24-52) and continuous treatment in adolescents (through week 52) from the phase 3, ICONIC-LEAD trial. Presented at: 2025 European Academy of Dermatology and Venerology Congress; September 17-20; Paris, France.