Johnson & Johnson Seeks EMA Approval for Oral IL-23 Antagonist Icotrokinra

Today, Johnson & Johnson announced that it has submitted a marketing authorization application to the European Medicines Agency (EMA) for icotrokinra (Protagonist Therapeutics and Janssen Biotech), a first-in-class oral peptide designed to selectively block the interleukin-23 (IL-23) receptor. The application seeks approval for use in adults and adolescents aged 12 years and older with moderate to severe plaque psoriasis (Pso).¹

Plaque psoriasis affects approximately 14 million people across Europe. Current systemic treatments include injectable biologics targeting cytokines such as IL-17 and IL-23, as well as oral therapies like deucravacitinib (Sotyktu; Bristol Myers Squibb), an allosteric TYK2 inhibitor.² Icotrokinra represents a novel approach as an oral therapy that directly targets the IL-23 receptor, a key driver of psoriatic inflammation.

“For people living with plaque psoriasis, the burden of disease goes far beyond the skin,” said Mark Graham, PhD, senior director, Therapeutic Area Head, Immunology Medical Affairs, Johnson & Johnson Innovative Medicine, in a news release. “This EMA filingrepresentsan important step in our efforts to advance plaque psoriasis care by broadening treatment options. Icotrokinra has the potential to offer complete skin clearance with afavourable safety profile, and simplicity in a once daily tablet, that allows patients to live their lives the way they'd like to.”

Clinical Development Program and Efficacy Data

The EMA submission includes data from 4 phase 3 randomized controlled trials (RCTs) conducted under the ICONIC development program: ICONIC-LEAD, ICONIC-TOTAL, ICONIC-ADVANCE 1, and ICONIC-ADVANCE 2. Across all studies, icotrokinra met primary and co-primary endpoints, demonstrating significant improvements in skin clearance in both adult and adolescent populations.¹

In the pivotal ICONIC-LEAD trial, icotrokinra achieved co-primary endpoints at week 16, with higher proportions of patients reaching Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1 compared with placebo. Subgroup analysis presented at the 2025 World Congress of Pediatric Dermatology showed that adolescents treated with icotrokinra achieved higher rates of clear or almost clear skin compared to placebo, with no new safety signals observed.

The ICONIC-TOTAL trial further supported efficacy in patients with psoriasis involving difficult to treat areas, including scalp, genital, and palmoplantar regions.

Results from ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 demonstrated superiority of icotrokinra over both placebo and deucravacitinib, another oral systemic option, in achieving co-primary endpoints. Secondary endpoints at weeks 16 and 24 also confirmed superiority over deucravacitinib.

Safety Profile

Safety outcomes across pooled analyses showed that adverse events (AEs) occurred in similar proportions of patients receiving icotrokinra (49.1%) compared with placebo (51.9%). No new or unexpected safety concerns were identified in any of the phase 3 studies. Long-term extension data, including outcomes beyond 52 weeks and results from randomized withdrawal analyses, are expected to be presented at upcoming scientific meetings.

Ongoing and Future Studies

The ICONIC program continues to expand. Johnson & Johnson has initiated ICONIC-ASCEND, the first head-to-head phase 3 trial evaluating an oral psoriasis therapy against an injectable biologic, ustekinumab (Stelara, Johnson & Johnson). This study is designed to assess whether icotrokinra can achieve superior efficacy compared with both ustekinumab and placebo.

Additional phase 3 studies, ICONIC-PsA 1 and ICONIC-PsA 2, are underway to evaluate icotrokinra in patients with active psoriatic arthritis, broadening the potential therapeutic scope of the agent in IL-23–mediated disease.

Conclusion

If approved, icotrokinra would be the first oral IL-23 receptor antagonist available for patients with moderate to severe plaque psoriasis. The therapy has demonstrated efficacy across multiple populations, including adolescents and those with challenging disease areas, with a favorable safety profile. The ongoing head-to-head ICONIC-ASCEND trial and forthcoming long-term data will provide further insights into its place among existing systemic therapies.

References

1. Johnson & Johnson seeks first European Medicines Agency approval for icotrokinra aiming to transform the plaque psoriasis treatment paradigm. News release. Johnso & Johnson. Published September 11, 2025. Accessed September 11, 2025. https://www.globenewswire.com/news-release/2025/09/11/3148479/0/en/Johnson-Johnson-seeks-first-European-Medicines-Agency-approval-for-icotrokinra-aiming-to-transform-the-plaque-psoriasis-treatment-paradigm.html
2. National Psoriasis Foundation. Psoriasis statistics. Accessed September 11, 2025. https://www.psoriasis.org/content/statistics