Three-quarters of adolescents with plaque psoriasis (PsO) treated with investigational icotrokinra (JNJ-2113) achieved completely clear skin with no new safety signals identified, according to data from a subgroup analysis of ICONIC-LEAD, the first ever Phase 3 registrational study in moderate-to-severe PsO that assessed efficacy and safety of a systemic therapy in adolescents and adults simultaneously.
Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the interleukin (IL)-23 receptor and is being studied in adults and adolescents aged 12 and older with moderate-to-severe plaque PsO.
These data were presented at the 2025 World Congress of Pediatric Dermatology (WCPD) Annual Meeting in Buenos Aires, Argentina.
Clear or Almost Clear
In the study, 84.1% of adolescent patients treated with once-daily icotrokinra achieved an Investigator’s Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 70.5% achieved a Psoriasis Area and Severity Index (PASI) 90 response, compared to 27.3% and 13.6% receiving placebo, respectively, at Week 16. Response rates continued to improve through Week 24, where 86.4% of adolescents achieved IGA 0/1 and 88.6% achieved PASI 90. Further, at Week 24, 75% of adolescents achieved IGA 0 and 63.6% achieved PASI 100.
“Data from the Phase 3 ICONIC LEAD subgroup analysis demonstrate impressive efficacy rates, showing the promise of this novel therapeutic option in the treatment of adolescents with moderate-to-severe plaque psoriasis who’ve often not yet received an advanced therapy,” says Lawrence Eichenfield, MD, Chief of Pediatric and Adolescent Dermatology at Rady Children’s Hospital-San Diego, and Professor of Pediatrics and Medicine (Dermatology), at the University of California, San Diego (UCSD) School of Medicine in San Diego, CA, ICONIC-LEAD presenter, in a news release. “Young patients with plaque psoriasis face unique challenges due to the visible and uncomfortable nature of the disease, making effective treatment options that align with their needs and preferences all the more important.”
Icotrokinra demonstrated a favorable safety profile. At Week 16, 50% of adolescents treated with icotrokinra experienced ≥1 adverse event (AE), compared to 73% of adolescents receiving placebo, with no new safety signals identified.
“Adolescents living with moderate-to-severe plaque psoriasis shouldn’t have to wait for effective treatments options that have the potential to deliver completely clear skin, which is the driving force for studying this younger population as part of the pivotal ICONIC program,” adds Liza O’Dowd, Vice President, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine. “These data underscore the promise of next-generation therapies and the potential for icotrokinra to offer adolescents with moderate-to-severe plaque psoriasis the unique combination of a favorable safety profile and complete skin clearance in a once-daily pill.”
About the ICONIC Studies
The pivotal Phase 3 ICONIC clinical development program of icotrokinra in adult and adolescent individuals with moderate-to-severe plaque PsO was initiated with two studies in Q4 2023 – ICONIC-LEAD and ICONIC-TOTAL – pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company.
ICONIC-LEAD is a Phase 3 randomized controlled trial evaluating the efficacy and safety of icotrokinra compared with placebo in 684 participants (icotrokinra=456; placebo=228) 12 years of age or older with moderate-to-severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-LEAD enrolled 66 adolescent patients.
ICONIC-TOTAL is an RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genitals, and/or hands and feet), with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.
Other Phase 3 studies in the development program include ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which are evaluating the efficacy and safety of icotrokinra compared with both placebo and deucravacitinib (Sotyktu, BMS) in adults with moderate-to-severe plaque PsO. ICONIC-ASCEND will evaluate the efficacy and safety of icotrokinra compared with placebo and ustekinumab in participants with moderate-to-severe plaque psoriasis. ICONIC-PsA 1 and ICONIC-PsA 2 will evaluate the efficacy and safety of icotrokinra compared to placebo in participants with active psoriatic arthritis.
