Icotrokinra Effective in High-Impact Psoriasis Areas

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Today, Johnson & Johnson released results from its phase 3 ICONIC-TOTAL study evaluating icotrokinra (JNJ-2113), an investigational first-in-class oral peptide that selectively targets the interleukin-23 (IL-23) receptor, at the Society for Investigative Dermatology meeting.¹ This receptor is implicated in the pathogenesis of moderate to severe plaque psoriasis (PsO), particularly in cases involving sensitive, high-impact skin sites such as the scalp, genitals, hands, and feet.²

The ICONIC-TOTAL study included both adults and adolescents (aged 12 years and older) with moderate plaque psoriasis, affecting at least 1% of body surface area (BSA). The trial assessed the efficacy and safety of once-daily icotrokinra treatment compared to placebo over a 16-week period.

Efficacy Outcomes

The study met its primary endpoint. At week 16, 57% of patients treated with icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin), with a ≥2-grade improvement from baseline. This response was significantly higher than the 6% observed in the placebo group (P<0.001).

In addition to the primary endpoint, several secondary outcomes were reported across difficult-to-treat anatomical regions:

• Scalp Psoriasis: Among patients with scalp involvement, 66% of those receiving icotrokinra achieved a scalp-specific IGA (ss-IGA) score of 0/1 compared to 11% in the placebo group (P<0.001).
• Genital Psoriasis: In patients with genital involvement, 77% achieved a static Physician's Global Assessment of Genitalia (sPGA-G) score of 0/1, versus 21% for placebo (P<0.001).
• Hand and/or Foot Psoriasis: In this smaller subset, 42% achieved a hand/foot PGA (hf-PGA) score of 0/1 compared to 26% in the placebo group, suggesting a potential but less definitive benefit in these areas.

These results highlight icotrokinra’s efficacy in skin regions often associated with disproportionate physical and psychological burden, despite their relatively small BSA involvement.

Safety Profile

Icotrokinra was generally well tolerated. Through week 16, adverse event (AE) rates were comparable between treatment arms—reported in 50% of the icotrokinra group and 42% of the placebo group. Serious adverse events occurred in 0.5% and 1.9% of icotrokinra and placebo patients, respectively. No new safety signals were observed, supporting a favorable short-term safety profile.

Clinical Context and Implications

Psoriasis in high-impact anatomical locations—such as the scalp, genitals, hands, and feet—is often more challenging to manage due to functional and psychosocial implications. Scalp involvement alone affects up to 80% of psoriasis patients, with these areas often resistant to conventional topical therapies and more difficult to reach with phototherapy.²

The ICONIC-TOTAL data build upon findings from earlier studies, including ICONIC-LEAD, and suggest that icotrokinra may provide a new oral treatment option that combines systemic efficacy with the convenience of once-daily dosing. As an oral peptide that selectively inhibits the IL-23 receptor, icotrokinra represents a mechanistically novel approach compared to existing biologics or non-specific systemic treatments.

Limitations and Future Directions

While the results are promising, longer-term data on durability of response and safety are still pending. The relatively small size of the hand/foot subgroup also limits the conclusiveness of those results. Researchers stated future studies will be necessary to confirm these findings in real-world settings and across broader patient populations, including those with comorbidities or treatment-resistant disease.

In conclusion, the study found icotrokinra demonstrates clinically meaningful efficacy and a favorable safety profile in patients with moderate plaque psoriasis, particularly in high-impact and sensitive anatomical areas. If approved, it may address an unmet need in the therapeutic landscape, offering a novel oral alternative to injectable biologics.

References

1. Icotrokinra results show significant skin clearance in patients with difficult-to-treat scalp and genital psoriasis. News release. PR Newswire. Published May 9, 2025. Accessed May 9, 2025. https://www.prnewswire.com/news-releases/icotrokinra-results-show-significant-skin-clearance-in-patients-with-difficult-to-treat-scalp-and-genital-psoriasis-302450309.html?tc=eml_cleartime
2. Ranzinger D, Eyerich K. Disease modification in psoriasis: Future prospects for long-term remission. Am J Clin Dermatol. Published online May 6, 2025. doi:10.1007/s40257-025-00949-5