Investigational TYK2 inhibitor looks good for atopic dermatitis

The investigational tyrosine kinase 2 (TYK2) inhibitor ICP-332 shows promise in the treatment of atopic dermatitis (AD), with phase II data showing favourable safety profile and efficacy.

The trial included 75 adults (72 percent male) with AD for at least 1 year and a history of contraindication or inadequate response to topical therapies. These patients were randomly assigned to receive treatment with ICP-332 at 80 or 120 mg (mean age 37.3 years) or placebo (mean age 44.5 years), administered orally once daily, for 4 weeks.  

Safety was the primary outcome, while the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4 was the key efficacy outcome. Other outcomes included percentages of patients achieving a ≥75-percent improvement in EASI (EASI-75) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with a ≥2-point improvement.

A total of 74 patients were included in the safety set. Adverse events (AEs) occurred in 17 of 25 patients (68 percent) in the placebo group, 19 of 25 (76 percent) in the 80-mg ICP-332 group, and 18 of 24 (75 percent) in the 120-mg ICP-332 group. All AEs were mild or moderate, and the most common was decreased blood fibrinogen (4 percent in the placebo group, 44 percent in the 80-mg ICP-332 group, and 21 percent in the 120-mg ICP-332 group).

At week 4, the percentage reductions in EASI were 78.2 percent (95 percent confidence interval [CI], −89.8 to −66.6) in the 80-mg ICP-332 group, 72.5 percent (95 percent CI, −84.3 to −60.7) in the 120-mg ICP-332 group, and 16.7 percent (95 percent CI, −28.7 to −4.6) in the placebo group. The differences observed between the ICP-332 groups and the placebo groups were significant (p<0.001 for both).

EASI-75 response rate was higher with ICP-332 vs placebo (64 percent in each dose group vs 56 percent; p<0.001). More patients who received 80-mg ICP-332 vs placebo achieved a Validated Investigator Global Assessment for Atopic Dermatitis score of 0/1 plus improvement of at least 2 points (difference, 32 percent; p=0.005).