Icotrokinra is the first IL-23 receptor targeted oral peptide that offers a myriad of benefits in moderate-to-severe plaque psoriasis.Data from two phase III ICONIC-ADVANCE studies presented at AAD 2026 reinforce the potential of the investigational first-in-class targeted oral peptide icotrokinra for the treatment of plaque psoriasis (PsO).
“There were robust rates of skin clearance and symptom relief that were durable or increased from week (W)24 to 52,” said the investigators, led by Dr Linda Stein Gold from the Henry Ford Health System, West Bloomingfield, Michigan, US.
In ICONIC-ADVANCE 1, three-quarters of participants overall achieved IGA* 0/1 with icotrokinra by W52. This effect was sustained from W24 among those who received icotrokinra from baseline, and a marked increase among those initially receiving deucravacitinib (52 percent at W24), more so among those who initially received placebo (11 percent at W16).
In ICONIC-ADVANCE 2, among icotrokinra recipients from baseline, the proportion of participants who achieved IGA 0/1 increased from 68 percent (W24) to 73 percent (W52). For those initially on deucravacitinib, a marked increase was observed between the two timepoints (from 55 percent to 80 percent). For placebo recipients who switched to icotrokinra, the rate rose substantially from 9 percent (W16) to 79 percent (W52).
Similarly, a high proportion of participants on icotrokinra achieved PASI* 90 response at W52 in both ICONIC-ADVANCE 1 (69–71 percent) and ICONIC-ADVANCE 2 (71–77 percent). [Gold, et al, AAD 2026]
Approximately 50 percent of icotrokinra recipients in both studies achieved complete skin clearance (IGA 0/PASI 100), with durable or increased response rates observed from W24 through W52, noted Gold and colleagues. “Of note, among deucravacitinib recipients, the rates of complete skin clearance increased by more than twofold after transitioning to icotrokinra at W24.”
Moreover, treatment with icotrokinra led to high rates of meaningful itch improvement and symptom resolution, with these rates sustained or increasing from W24 to W52. The proportions of participants who achieved clinically meaningful improvements in PSSD* Itch Score were 73–81 percent in ICONIC-ADVANCE 1 and 76–84 percent in ICONIC-ADVANCE 2. The corresponding percentages of patients achieving PSSD Symptom Score 0 were 38–45 percent and 33–45 percent, respectively.
In a pooled analysis of both trials, icotrokinra recipients had a mean percent PASI improvement of 91 percent at W52. The curves between icotrokinra and placebo diverged as early as W2. Of note, the mean percent PASI improvement at W16 was substantially greater with the experimental agent than with placebo (84 percent vs 27 percent; nominal p<0.001).
The safety profile of icotrokinra at W52 aligned with that reported at W16 and W24, with no new safety signals identified. Of note, the infection rate at W24 was lower with the active agent vs deucravacitinib (31 percent vs 40 percent).
“Patients with moderate-to-severe plaque PsO are limited to injectable therapies to achieve high-level efficacy with a favourable safety profile,” Gold noted. Icotrokinra is the first and only targeted oral peptide that precisely blocks the interleukin (IL)-23 receptor and inhibits IL-23 pathway signaling. [Sci Rep 2024;14:17515]
In ICONIC-ADVANCE 1, 774 participants were randomized 2:1:2 to icotrokinra 200 mg, placebo, or deucravacitinib 6 mg QD until W156. Placebo recipients switched to icotrokinra by W16; those on deucravacitinib did so by W24. The average age of participants was approximately 47 years, about a third were women, and nearly a quarter were Asian.
In ICONIC-ADVANCE 2, 731 participants were randomized 4:1:4 to the same treatment regimens as in ICONIC-ADVANCE 1. The average participant age was about 46 years, 33 percent were women, and <15 percent were Asian.
Across both trials, about 80 percent of participants had moderate disease (IGA score 3) while the rest had severe disease (IGA score 4). The average baseline PSSD symptom and itch scores were 50 and 6, respectively. Approximately three-quarters of participants received prior systemic therapy**, with about a quarter receiving biologics***.
“As the first IL-23 receptor targeted oral peptide, icotrokinra offers a combination of benefits in moderate-to-severe plaque PsO,” Gold noted in a press release. “These 1‑year results show how innovation is redefining care and delivering the lasting outcomes patients have been waiting for.”
“The icotrokinra 1-year data highlight the impact of targeted science in addressing real-world patient needs. Across age groups, high‑impact disease sites, and head‑to‑head trials, the results point to a new systemic therapy that can move the needle on treatment gaps in plaque PsO,” noted Dr Liza O’Dowd from Johnson & Johnson.