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

Abstract

D-2570, a TYK2 inhibitor, is currently being developed for autoimmune diseases including psoriasis and ulcerative colitis. To evaluate the efficacy and safety of D-2570 in patients with moderate-to-severe plaque psoriasis. 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. At week 12, significantly higher response rates for PASI 75 (85.0% to 90.0%, vs 12.5%, P < .001 for all), PASI 90 (70.7% to 77.5% vs 5.0%, P < .001), PASI 100 (39.0% to 50.0% vs 2.5%, P < .005) and sPGA 0/1 (80.5% to 87.5% vs 20.0%, P < .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. Small sample size, relatively short duration of treatment and follow-up. D-2570 demonstrated a high efficacy with favorable safety profile in patients with moderate-to-severe plaque psoriasis.