Oral IL-23 Blocker Shows Durable Psoriasis Control at 1 Year

At the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Jennifer Soung, MD, presented 1-year data from the pivotal ICONIC-LEAD trial evaluating icotrokinra (Johnson & Johnson), the first-in-class oral peptide that selectively binds the interleukin-23 (IL-23) receptor. The results underscored durable efficacy and a favorable safety profile in both adults and adolescents with moderate to severe plaque psoriasis.¹

“Biologics that target IL-23 are well established with excellent efficacy and a favorable safety profile,” Soung noted. “However, there are still many patients with moderate to severe plaque psoriasis who are untreated, and one of the reasons may be that patients prefer pills rather than injections.”² Icotrokinra, she explained, represents a novel therapeutic alternative: a once-daily oral IL-23 antagonist designed to offer the efficacy of injectable biologics in a pill form.

The ICONIC-LEAD trial enrolled nearly 700 patients aged 12 years and older with moderate to severe plaque psoriasis. Participants had to meet strict inclusion criteria, including a Psoriasis Area and Severity Index (PASI) score of at least 12, body surface area involvement of 10% or greater, and candidacy for systemic therapy or phototherapy. Adults received icotrokinra 200 mg once daily for 24 weeks. Responders, defined as those achieving PASI 75 or an Investigator’s Global Assessment (IGA) score of 0 or 1 at week 24, were re-randomized to continue icotrokinra or switch to placebo through week 52. Adolescents, by contrast, remained on continuous treatment for the full year.

In adults, the durability of response was striking. “Almost 90% of patients achieved a PASI 75 at week 52, and 84% maintained PASI 90,” Soung reported. Clear or almost clear skin (IGA 0/1) was sustained in 82% of patients continuing therapy. Patients who were withdrawn from treatment experienced gradual relapse. On average, it took 17 weeks for half of the placebo group to lose their PASI 75 response and 10 weeks to lose PASI 90, results consistent with the known durability of IL-23 pathway inhibition.

Adolescents showed particularly robust responses. Soung emphasized, “I have never seen 100%—all icotrokinra-randomized adolescents achieved PASI 75 by week 32, with response rates maintained in the 90th percentile through week 52.” By week 24, nearly 90% of adolescent patients had achieved PASI 90 or IGA 0/1, and these improvements remained stable through 1 year.

Safety findings between weeks 16 and 52 were favorable and consistent across both age groups. Rates of serious infections and malignancy remained under 1%, with no active cases of tuberculosis reported. “The safety signals are consistent with what we already know about the IL-23 target,” Soung stated, underscoring the reassuring long-term tolerability profile of icotrokinra.

Soung concluded with 3 key takeaways: continuous icotrokinra treatment maintained high levels of skin clearance in adults, withdrawal from therapy led to a predictable decline in response, and adolescents demonstrated remarkably durable and robust outcomes. “Icotrokinra adverse event profile was favorable and consistent,” she summarized.

The ICONIC-LEAD trial positions icotrokinra as a potential first oral IL-23 inhibitor for moderate to severe plaque psoriasis. For patients reluctant to initiate injectable biologic therapy, an oral option could improve accessibility and adherence while maintaining the high efficacy associated with IL-23 inhibition. Longer-term follow-up and real-world data will be essential, but these 1-year findings presented at EADV represent an important step forward in expanding systemic treatment options for psoriasis.

References

1. 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.
2. Biologics. The National Psoriasis Foundation. Accessed September 17, 2025.