Biomaterial Database

Novel TYK2 inhibitor D-2570 in moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase 2 trial. 2025

Jianzhong Zhang, and Cheng Zhou, and Guoying Miao, and Shoumin Zhang, and Xinsuo Duan, and Liming Wu, and Guoqiang Zhang, and Ningning Dang, and Yangfeng Ding, and Hongfang Han, and Aihua Wei, and Bin Yang, and Linfeng Li, and Shanshan Li, and Xunyi Dai, and Jianglin Zhang, and Tiechi Lei, and Wenjie Yan, and Lixia Zhang, and Zudong Meng, and Rixin Chen, and Qiuhe Song, and Liangchun Wang, and Wenhui Wang, and Xinglin Hu, and Ziyong Xiang, and Zhe Shi, and Ling Zhang

Department of Dermatology, Peking University People's Hospital, Beijing, China. Electronic address: rmzjz@126.com.

BACKGROUND D-2570, a TYK2 inhibitor, is currently being developed for autoimmune diseases including psoriasis and ulcerative colitis. OBJECTIVE To evaluate the efficacy and safety of D-2570 in patients with moderate-to-severe plaque psoriasis. METHODS In the randomized, double-blind, phase 2 study (NCT06278350), patients were randomized 1:1:1:1 to receive D-2570 at 18/27/36 mg, or placebo once daily for 12 weeks. The primary endpoint was the proportion of patients achieving psoriasis area severity index (PASI) 75 at week 12. Secondary endpoints included PASI 75/90/100 and static Physician Global Assessment (sPGA) score of 0/1, safety, and pharmacokinetic/pharmacodynamic characteristics. RESULTS At week 12, significantly higher response rates for PASI 75 (85.0%-90.0%, vs 12.5%, p<0.001 for all), PASI 90 (70.7%-77.5% vs 5.0%, p<0.001), PASI 100 (39.0%-50.0% vs 2.5%, p<0.005) and sPGA 0/1 (80.5%-87.5% vs 20.0%, p<0.001) were achieved in patients receiving D-2570 at 18/27/36 mg versus placebo. D-2570 was well tolerated, and most treatment-emergent adverse events were mild/moderate. D-2570 exhibited favorable pharmacokinetic properties and effectively suppressed IL-17A levels in patients. CONCLUSIONS small sample size, relatively short duration of treatment and follow-up. CONCLUSIONS D-2570 demonstrated a high efficacy with favorable safety profile in patients with moderate to severe plaque psoriasis.