Oral TYK2 Inhibitor Socrodeucitinib Meets Primary Endpoint in Phase 2 Psoriasis Trial

Socrodeucitinib (HS-10374), an investigational oral tyrosine kinase 2 (TYK2) inhibitor, demonstrated significant improvements in skin clearance and disease severity in patients with moderate to severe plaque psoriasis, according to results from a randomized phase 2 trial.¹ The 12-week study found that the drug met its primary endpoint, with the 12-mg once-daily dose producing substantially higher rates of PASI 75, PASI 90, and PASI 100 responses compared with placebo while maintaining a generally favorable safety profile.

Mechanism of Action and Study Design

TYK2 is a key component of the JAK-STAT signaling pathway and mediates downstream signaling from cytokines including IL-12, IL-23, and type I interferons, all of which play important roles in psoriasis pathogenesis. Unlike broader JAK inhibitors, socrodeucitinib is an allosteric inhibitor that selectively binds the TYK2 pseudokinase domain, limiting activity against JAK1, JAK2, and JAK3.² The study's primary endpoint was the proportion of patients achieving a 75% reduction in Psoriasis Area and Severity Index (PASI) score at week 12.

The multicenter, double-blind, placebo-controlled trial enrolled 125 adults with moderate to severe plaque psoriasis across 38 centers in China between September 2023 and April 2024. Participants were randomized 1:1:1 to receive oral socrodeucitinib 6 mg, socrodeucitinib 12 mg, or placebo once daily for 12 weeks. Eligible patients were aged 18 to 70 years and had plaque psoriasis for at least 6 months with a PASI score of 12 or greater, body surface area involvement of at least 10%, and a static Physician's Global Assessment (sPGA) score of 3 or higher.

Primary Endpoint and High-Level Skin Clearance

Investigators reported statistically significant improvements with both active treatment groups, although responses were markedly greater with the higher dose. By week 12, PASI 75 was achieved by 72.1% of patients receiving socrodeucitinib 12 mg compared with 28.6% of those receiving the 6-mg dose and 7.5% of patients receiving placebo. Both treatment groups significantly outperformed placebo, with the strongest efficacy observed in the 12-mg cohort.

Higher levels of skin clearance also favored the 12-mg dose. PASI 90 was achieved by 46.5% of patients receiving socrodeucitinib 12 mg compared with 7.1% in the 6-mg group and no patients receiving placebo. Complete skin clearance (PASI 100) occurred in 11.6% of patients treated with the 12-mg dose versus 2.4% with the 6-mg dose and none in the placebo group.

Onset of Response and Secondary Outcomes

Clinical responses emerged early during treatment. PASI 75 responses became apparent by week 4, while improvements in overall PASI scores and percentage reductions from baseline were observed as early as week 2 and were maintained throughout the 12-week treatment period. Additional efficacy measures also favored socrodeucitinib. At week 12, 65.1% of patients receiving the 12-mg dose achieved an sPGA score of 0 or 1 (clear or almost clear skin), compared with 33.3% in the 6-mg group and 10% in the placebo group.

MORE ON PSORIASIS

Patients treated with socrodeucitinib also experienced greater improvements in body surface area involvement and dermatology-specific quality of life. Both active treatment groups demonstrated significantly greater reductions in affected body surface area than placebo. Improvements in Dermatology Life Quality Index (DLQI) scores were also significantly greater with socrodeucitinib, particularly with the 12-mg dose, with benefits evident by week 4 and sustained through week 12.

Exposure-response analyses further supported dose selection. Investigators found that PASI 75 response rates increased with higher steady-state drug exposure and approached a plateau at the exposure achieved with the 12-mg once-daily regimen.

Safety Profile and Phase 3 Advancement

Safety findings were generally consistent across treatment groups. Overall adverse events occurred in 70.0% of patients receiving placebo, 76.2% of those receiving socrodeucitinib 6 mg, and 88.4% of those receiving the 12-mg dose. Most adverse events were grade 1 or 2 in severity. Upper respiratory tract infection was the most common adverse event and showed some dose dependency, occurring in 7.5% of placebo-treated patients, 16.7% of patients receiving 6 mg, and 23.3% of those receiving 12 mg.

Fever, sinus bradycardia, and sinus arrhythmia were also reported but were generally mild. Serious adverse events were uncommon, and the investigators also reported no clinically meaningful trends in laboratory abnormalities involving liver function, lipid parameters, hematologic measures, or renal function.

Based on the efficacy and exposure-response findings, the investigators selected the 12-mg once-daily dose for ongoing phase 3 evaluation. They concluded that larger, longer-duration studies are needed to further establish the efficacy and safety of socrodeucitinib in patients with moderate to severe disease.

References

1. Han L, Geng S, Ding Y, et al. A randomized phase 2 trial of socrodeucitinib in moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. Published online July 28, 2026. doi:10.1111/jdv.70643

2. Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain. J Biol Chem. 2015;290(17):11061-11074. doi:10.1074/jbc.M114.619502