IIcotrokinra Shows Promise in Psoriasis

Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor and is being studied in adults and adolescents 12 years of age and older with moderate-to-severe plaque PsO.

Data from the Phase III ICONIC-LEAD study, presented as a late-breaking abstract at the 2025 American Academy of Dermatology (AAD) Annual Meeting, show once daily icotrokinra demonstrated significant skin clearance and a favorable safety profile in adults and adolescents 12 years of age and older with moderate-to-severe plaque PsO.

In the ICONIC-LEAD study, nearly two-thirds (65%) of patients treated with once daily icotrokinra achieved an Investigator’s Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 50% achieved a Psoriasis Area and Severity Index (PASI) 90 response, compared to 8% and 4% receiving placebo, respectively (P<0.001 for both endpoints) at Week 16. Continued skin clearance improvement was reported at Week 24 with 74% of patients treated with icotrokinra achieving IGA 0/1 and 65% achieving PASI 90. At Week 24, nearly half of patients treated with icotrokinra achieved completely clear skin – 46% reached IGA 0 and 40% reached PASI 100. Similar proportions of patients experienced adverse events (AEs) between icotrokinra (49%) and placebo groups (49%), with no new safety signals identified.

Results from a subgroup analysis of the ICONIC-LEAD study evaluating icotrokinra in the adolescent population will be presented at a forthcoming medical meeting.

“People living with moderate-to-severe plaque psoriasis are seeking options that balance efficacy, safety and ease of use,” said Robert Bissonnette, M.D., Chairman at Innovaderm Research, Montreal, Canada and ICONIC-LEAD study investigator. “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.”

Additionally, topline results show that the Phase III ICONIC-ADVANCE 1&2 studies met their co-primary endpoints of IGA 0/1 and PASI 90 versus placebo at Week 16. Icotrokinra also met all key secondary endpoints at Weeks 16 and 24 that measured superiority to deucravacitinib in patients with moderate-to-severe plaque PsO. Based on the positive outcomes of the ADVANCE studies, Johnson & Johnson is initiating the Phase III ICONIC-ASCEND study, the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab representing an important step forward in psoriasis research.

“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, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine. “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.” 

About the ICONIC Clinical Development Program
The pivotal Phase III ICONIC clinical development program of icotrokinra (JNJ 2113) 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 & Johson company.

ICONIC-LEAD (NCT06095115) is a Phase III randomized controlled trial (RCT) 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 (NCT06095102) is a 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, genital, 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 III studies in the development program include ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), which are evaluating the efficacy and safety of icotrokinra compared with both placebo and deucravacitinib 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 2 (NCT06807424) will evaluate the efficacy and safety of icotrokinra compared to placebo in participants with active psoriatic arthritis.