ICP-332 Effective, Safe for Treating Moderate to Severe Atopic Dermatitis

Once-daily oral ICP-332 therapy has demonstrated notable efficacy and a favorable safety profile in the treatment of patients with atopic dermatitis, according to new data.1

Jinhua Xu, PhD, of Fudan University’s Huashan Hospital in Shanghai, authored this paper alongside a team of other investigators, and it was published in JAMA Dermatology. Xu and coauthors set out to assess ICP-332, a tyrosine kinase 2 (TYK2) inhibitor, in moderate to severe atopic dermatitis.

This oral small-molecule TYK2 inhibitor was formulated to selectively bind to the TYK2 catalytic domain JH1. The drug can help to block signal transduction of inflammatory cytokines among patients.2 It was evaluted by the investigators in this new, phase 2 study.

“Herein, we evaluate the safety and efficacy of ICP-332 in patients with moderate to severe [atopic dermatitis] in a double-blind, placebo-controlled phase 2 randomized clinical trial,” Xu and colleagues wrote.1

Trial Design Details

Xu et al’s phase 2 randomized clinical trial implemented a double-blind, placebo-controlled, multi-center design, with their research being conducted across 19 clinical sites within China. The study took place between February - November 2023. A screening phase was included during the protocol, lasting up to 35 days. This was followed by a 4-week double-blind treatment period and then a safety follow-up period lasting 28 days.

Adults between 18 - 75 years of age were considered eligible if they had a documented history of atopic dermatitis for a single year minimum prior to the initial dose of ICP-332. The diagnosis of this condition was confirmed at the time of patient screening via the Williams criteria. Subjects were required, to qualify as having moderate to severe disease, to have an Eczema Area and Severity Index (EASI) score of 16 or greater. They would also have to show involvement of at least 10% of body surface area as well as a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or greater at the point of baseline.

Race and ethnicity were self-identified by participants and collected to explore whether these factors influenced treatment outcomes. Eligible individuals also needed a documented inadequate response to topical corticosteroids or topical calcineurin inhibitors, defined as use for a minimum of 4 weeks within the year prior to screening, or a clinical reason that made topical therapy inappropriate. To minimize confounding effects from prior therapies, use of Janus kinase inhibitors or other biologic agents within 12 weeks before the first dose was not permitted, and conventional systemic treatments were prohibited within 4 weeks of study entry.

In a 1:1:1 ratio, participants were randomly assigned to be treated with oral ICP-332 at a 80 mg dose, at 120 mg, or placebo once-per-day for 4 weeks. The trial subjects and study investigators remained blinded to treatment allocation throughout the study’s double-blind period. Safety served as the analysis’s main endpoint. Xu and coauthors’ principal efficacy endpoint was the percentage change from baseline in participants’ EASI score at the 4-week mark. Among other efficacy assessments, the team also evaluated the proportion of participants attaining at least a 75% reduction in EASI (EASI-75) and the proportion achieving a vIGA-AD score of 0 (clear) or 1, with an improvement of at least 2 points from the point of baseline.

Findings on ICP-332

There were 75 patients recruited in Xu et al’s study. ICP-332 demonstrated a favorable safety profile among these patients, with most adverse events (AEs) classified as mild in their level of disease severity. There were no instances of death or any AEs considered to be serious taking place during the analysis. By the 4-week mark, mean placebo-adjusted EASI reductions from baseline were −61.6% for individuals on 80 mg of ICP-332 and −55.8% for those in the 120-mg dosing cohort. These findings indicated substantial disease severity improvements compared with placebo.

“In this phase 2 randomized clinical trial, ICP-332 monotherapy was efficacious and demonstrated a favorable benefit-risk profile compared with placebo in adults with moderate to severe [atopic dermatitis], supporting initiation of larger randomized, controlled, phase 3 studies to confirm its potential as an effective treatment for this population,” the team concluded.1

References

1. Xu J, Zhang L, Liang Y, et al. Safety and Efficacy of ICP-332 for Moderate to Severe Atopic Dermatitis: A Phase 2 Randomized Clinical Trial. JAMA Dermatol. Published online January 14, 2026. doi:10.1001/jamadermatol.2025.5295.

2. Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3):110. doi:10.4172/2155-9899.1000110.