Icotrokinra Bests Placebo in Psoriasis, Aims for Head-to-Head with Ustekinumab

Results of a phase 3 trial suggest icotrokinra, a first-in-class oral peptide that selectively blocks the IL-23 receptor from Johnson and Johnson, helped nearly 50% of patients aged 12 years and older with moderate to severe plaque psoriasis at 24 weeks.

Based on these data from the ICONIC-LEAD trial, as well as positive topline data from the ICONIC-ADVANCE 1 and 2 studies, which found the agent outperformed deucravacitinib for superiority in patients with moderate-to-severe plaque psoriasis, Johnson and Johnson has announced their intent to launch the ICONIC-ASCEND study. According to Johnson and Johnson, ICONIC-ASCEND will be the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill compared to an injectable biologic in moderate-to-severe psoriasis.2,3

"People living with moderate-to-severe plaque psoriasis are seeking options that balance efficacy, safety and ease of use," said principal investigator Robert Bissonnette, MD, chairman at Innovaderm Research, Montreal, Canada, who presented the ICNONIC-LEAD data at 2025 American Academy of Dermatology (AAD) Annual Meeting.2 "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."

A phase 3 multicenter, randomized, double-blind, placebo-controlled conducted at 170 sites across multiple continents, the ICONIC-LEAD trial was launched in October 2023 to explore the safety and efficacy of icotrokinra relative to placebo therapy among patients with moderate to severe plaque psoriasis. The trial enrolled 684 individuals aged 12 years and older and randomized them in a 2:1 ratio to receive icotrokinra or placebo, with 456 receiving icotrokinra and 228 received placebo therapy.1,2,3,4

The coprimary outcomes of interest for the study were achievement of Investigator's Global Assessment (IGA) score of 0 or 1, which indicates clear or almost clear skin, and achievement of a Psoriasis Area and Severity Index (PASI) 90 response.1,2,3,4

Results of the ICONIC-LEAD showcased at AAD 2025 suggest 65% of patients receiving icotrokinra achieved an IGA score of 0 or 1 compared to 8% of the placebo group (P <.001) at week 16. When assessing PASI 90 response, results indicated a rate of achievement of 50% with icotrokinra and 4% with placebo (P <.001).1,2,3

Further analysis suggested 46% of the icotrokinra reached IGA 0 and 40% reached PASI 100 at week 24. Additionally, 74% of patients receiving icotrokinra achieved an IGA score of 0 or 1 and 65% achieved PASI 90 at week 24. Analysis of safety data suggested adverse events were reported by 49% of the icotrokinra arm and 49% of the placebo arm, with no new safety signals observed within the trial.1,2,3

According to a release from Johnson and Johnson, topline data from the ICONIC-ADVANCE 1 and 2 trials suggest the trials met their coprimary endpoints of IGA score of 0 or 1 and PASI 90 versus placebo at week 16 as well as key secondary endpoints at weeks 16 and 24 assessing superiority relative to deucravacitinib in patients with moderate-to-severe plaque psoriasis.2,3

"The robust results seen to date underscore the potential for icotrokinra to shift treatment expectations in moderate-to-severe plaque psoriasis," said Liza O'Dowd, vice president and disease area lead for Immunodermatology at Johnson & Johnson Innovative Medicine.2 "As part of our ongoing commitment to pioneer innovations for patients, we are proud to advance this first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, which shows promise as a potential first-line systemic therapy for the treatment of plaque psoriasis."

References:

1. Bissonnette R. Icotrokinra, a Targeted Oral Peptide That Selectively Blocks the Interleukin-23–Receptor, for the Treatment of Moderate-to-Severe Plaque Psoriasis. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.

2. Johnson and Johnson. ICOTROKINRA results show potential to set a new standard of treatment in plaque psoriasis. JNJ.com. March 8, 2025. Accessed March 8, 2025. https://www.jnj.com/media-center/press-releases/icotrokinra-results-show-potential-to-set-a-new-standard-of-treatment-in-plaque-psoriasis.

3. Protagonist Therapeutics, Inc. ICOTROKINRA clinical study results demonstrate its potential to shift treatment paradigm and set a new standard for treatment in plaque psoriasis. ACCESSWIRE Newsroom. March 8, 2025. Accessed March 8, 2025. https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/icotrokinra-clinical-study-results-demonstrate-its-potential-to-shift-997630.

4. ClinicalTrials.gov. A Study of JNJ-77242113 in Adolescent and Adult Participants With Moderate to Severe Plaque Psoriasis (ICONIC-LEAD). Clinicaltrials.gov. February 11, 2025. Accessed March 8, 2025. https://clinicaltrials.gov/study/NCT06095115.