Phase 2 TYK2 Inhibition Shows Promise in AD

The therapeutic landscape for atopic dermatitis (AD) has expanded rapidly over the past decade, yet many patients with moderate to severe disease continue to experience inadequate disease control, treatment-related burden, or safety concerns. Small-molecule inhibitors targeting intracellular signaling pathways have emerged as a potential strategy to address unmet needs, particularly for patients seeking effective oral options.¹ With this in mind, JAMA Dermatology recently published results from a phase 2 randomized clinical trial evaluating soficitinib (ICP-332; InnoCare), a novel and selective tyrosine kinase 2 (TYK2) inhibitor, in adults with moderate to severe AD.^2-3

The study was a double-blind, placebo-controlled phase 2 trial designed to assess both safety and early efficacy signals. A total of 75 participants were randomized in a 1:1:1 ratio to receive oral soficitinib at doses of 80 mg or 120 mg once daily, or matching placebo, over a 4-week treatment period. Baseline disease severity reflected a population with clinically meaningful disease activity. The primary objective was to evaluate safety and efficacy, with the key efficacy endpoint defined as the percentage change from baseline in the Eczema Area and Severity Index (EASI) score at week 4. Secondary and exploratory endpoints included the proportion of patients achieving EASI-75, improvements in the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), pruritus outcomes, and patient-reported quality of life measures.

At week 4, researchers found both soficitinib dose groups demonstrated substantial reductions in disease severity compared with placebo. Mean percentage improvement from baseline in EASI was 78.2% in the 80 mg group and 72.5% in the 120 mg group, compared with 16.7% in the placebo arm. These changes translated into clinically relevant response rates, with 64.0% of patients in each soficitinib group achieving EASI-75, versus a markedly lower response in the placebo group. Improvements in global disease assessment were also observed, particularly in the 80 mg group, where a higher proportion of patients achieved a vIGA-AD score of clear or almost clear with at least a 2-point improvement compared with placebo (36.0% vs 4.0%; P=0.005).

Beyond objective measures of skin inflammation, the trial highlighted a rapid and meaningful effect on pruritus, a symptom that often drives disease burden and impairs daily functioning in AD. Reductions in pruritus severity and frequency, measured by the Pruritus Numerical Rating Scale, were evident as early as day 2 of treatment in both active treatment arms. Improvements continued over the 4-week period, with peak effects observed at week 4. Notably, 72.0% of patients receiving either dose of soficitinib achieved a reduction of at least 4 points in pruritus severity by week 4, compared with 16.0% in the placebo group. These symptomatic improvements were accompanied by consistent gains in quality of life, as assessed by the Dermatology Life Quality Index (DLQI), with statistically significant differences favoring soficitinib at weeks 1, 2, and 4.

From a safety perspective, soficitinib was generally well tolerated over the short study duration. Treatment-emergent adverse events were predominantly mild or moderate in severity, and no unexpected safety signals were reported. All adverse events in the 80 mg group were classified as mild, a profile comparable to placebo. While the limited sample size and short follow-up restrict conclusions about long-term safety, the findings suggest a favorable early benefit–risk balance consistent with selective TYK2 inhibition.

Mechanistically, TYK2 plays a role in signaling pathways relevant to type 2 inflammation and immune regulation, making it an attractive target for AD and other immune-mediated dermatologic conditions. The observed efficacy across skin signs, pruritus, and quality of life supports the biological rationale for targeting this pathway, while the oral administration may offer practical advantages for certain patient populations.

Investigators emphasized that these results represent an early step in clinical development. As Jinhua Xu, PhD, of Huashan Hospital, Fudan University, noted, the phase 2 data support further investigation, and enrollment has now been completed for a larger phase 3 program in moderate to severe AD. That study, involving 579 patients, is expected to provide more definitive information on durability of response, dose optimization, and longer-term safety.

In summary, this phase 2 randomized clinical trial suggests that soficitinib may offer rapid, clinically meaningful improvements in disease severity and pruritus for patients with moderate to severe atopic dermatitis, with a tolerability profile comparable to placebo over 4 weeks. While confirmatory data from phase 3 trials will be essential before defining its place in therapy, these findings add to the growing body of evidence supporting selective TYK2 inhibition as a promising approach in inflammatory skin disease.

References

1. Anderson P, Austin J, Lofland JH, Piercy J, Joish VN. Inadequate disease control, Treatment Dissatisfaction, and Quality-of-Life Impairments Among US Patients Receiving Topical Therapy for Atopic Dermatitis. Dermatol Ther (Heidelb). 2021;11(5):1571-1585. doi:10.1007/s13555-021-00580-2
2. 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
3. Study results of novel TYK2 inhibitor soficitinib in patients with AD published by JAMA Dermatology. News release. Published January 29, 2026. Accessed January 30, 2026. https://www.biospace.com/press-releases/study-results-of-novel-tyk2-inhibitor-soficitinib-in-patients-with-ad-published-by-jama-dermatology