EADV: Icotrokinra maintains long-term efficacy, safety for plaque psoriasis

EADV: Icotrokinra maintains long-term efficacy, safety for plaque psoriasis | Image Credit: © SNAB - © SNAB - stock.adobe.com.

New 52-week data from the phase 3 ICONIC-LEAD study (NCT06095115) showed that icotrokinra, a first-in-class targeted oral peptide that selectively blocks the IL-23 receptor, sustained high rates of skin clearance in adults and adolescents with moderate-to-severe plaque psoriasis. Findings were presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France.^1,2

At week 52, 84% of adult patients who achieved a 90% reduction in Psoriasis Area and Severity Index (PASI90) at week 24 and were re-randomized to continue icotrokinra maintained their responses, compared with 21% of those switched to placebo (P < 0.001). Among adolescents, 86% of patients who continued icotrokinra for the full 52 weeks and 77% of those switched from placebo at week 16 achieved PASI90. No new safety signals were identified, and adverse event (AE) rates remained consistent with earlier findings.²

“These results reinforce the potential of icotrokinra to provide durable efficacy across both adult and pediatric populations, with a favorable safety profile,” Protagonist Therapeutics stated in the press release.

The data comes after a New Drug Application (NDA) was submitted for icotrokinra on July 21, 2025, to the FDA to treat patients 12 years and older with moderate-to-severe plaque psoriasis. The NDA submission was based on previous data from the ICONIC-LEAD study, presented at the 2025 American Academy of Dermatology Annual Meeting.³

READ MORE: J&J submits icotrokinra NDA for plaque psoriasis in patients 12 years or older

"People living with moderate to severe plaque psoriasis are seeking options that balance efficacy, safety, and ease of use,” said Robert Bissonnette, MD, chair of Innovaderm Research in Montreal, Quebec, Canada, and ICONIC-LEAD study investigator, at the time of data announcement. "These study results are promising and show the potential for treatment with icotrokinra to offer patients the unique combination of complete skin clearance and a favorable safety profile in a once-daily pill.”²

ICONIC-ADVANCE 1 and 2: superiority to deucravacitinib

Additional data from the ICONIC-ADVANCE 1 and 2 trials highlighted the superiority of icotrokinra over deucravacitinib in adults with moderate-to-severe plaque psoriasis.¹

In both studies, icotrokinra met co-primary endpoints versus deucravacitinib at week 16, with significantly greater proportions of patients achieving an Investigator’s Global Assessment (IGA) score of clear or almost clear (IGA0/1) and PASI90. At week 16, 68%/70% of patients on icotrokinra achieved IGA0/1 compared with 50%/54% on deucravacitinib, while PASI90 responses were 55%/57% in the icotrokinra group compared to 30%/34% in the deucravacitinib group.

At week 24, 74%/68% of patients on icotrokinra achieved IGA0/1 compared with 52%/55% on deucravacitinib. PASI90 results also favored icotrokinra, as 66%/65% achieved the co-primary endpoint compared to 41%/43% in the deucravacitinib group.

Rates of AEs were similar between icotrokinra and placebo and were numerically lower compared with deucravacitinib, with infections such as nasopharyngitis and upper respiratory tract infections being the most common.^1,2

Next steps in psoriasis research

Beyond ICONIC-LEAD and ICONIC-ADVANCE, Protagonist and Johnson & Johnson have launched the ICONIC-ASCEND study, the first head-to-head phase 3 trial designed to compare an oral psoriasis therapy, icotrokinra, with an injectable biologic, ustekinumab.²

"Icotrokinra has the potential to set a new standard of treatment for psoriasis patients with a once-daily targeted oral therapy that selectively blocks the IL-23 receptor," said Dinesh V. Patel, PhD, president and chief executive officer of Protagonist Therapeutics.²

References:

1. Gold LS, Armstrong AW, Bissonnette R, et al. Icotrokinra Demonstrated Superior Responses Compared With Placebo and Deucravacitinib in the
   Treatment of Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3 ICONIC-ADVANCE 1&2 Studies. Abstract. Presented at: 2025 European Academy of Dermatology and Venereology (EADV) Congress. Paris, France.
2. Protagonist Announces Presentations of Clinical Data with Icotrokinra in Plaque Psoriasis and Preclinical Data with PN-881 at the EADV 2025 Congress. Protagonist. Press release. September 17, 2025. Accessed September 18, 2025. https://feeds.issuerdirect.com/news-release.html?newsid=7528099530969780&symbol=PTGX
3. Fitch J. J&J submits icotrokinra NDA for plaque psoriasis in patients 12 years or older. Contemporary Pediatrics. July 21, 2025. Accessed September 18, 2025. https://www.contemporarypediatrics.com/view/j-j-submits-icotrokinra-nda-for-plaque-psoriasis-in-patients-12-years-and-up