Tapinarof cream for the treatment of atopic dermatitis: Efficacy and safety results from two Japanese phase 3 trials

Abstract Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream 1% in Japanese patients aged ≥12 years with atopic dermatitis (AD) in two phase 3 trials, ZBB4‐1 and ZBB4‐2. ZBB4‐1 ( N = 216) consisted of an 8‐week, double‐blind, vehicle‐controlled treatment period (period 1) and a 16‐week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who enrolled in period 2 received tapinarof. ZBB4‐2 ( N = 291) was a 52‐week, open‐label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBB4‐1, the proportion of patients who achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with ≥2‐grade improvement from baseline at week 8 (IGA treatment success, the primary end point) was 20.24% in the tapinarof group and 2.24% in the vehicle group ( p = 0.0007). The proportion of patients with ≥75% improvement from baseline in Eczema Area and Severity Index (EASI) score at week 8 (EASI‐75 response, the key secondary end point) was 40.3% in the tapinarof group and 4.3% in the vehicle group ( p < 0.0001). In ZBB4‐2, IGA treatment success rate was 28.1% at week 16, 32.3% at week 24, and 41.3% at week 52, and EASI‐75 response rate was 53.3% at week 16, 63.7% at week 24, and 76.6% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis, acne, and headache. In summary, tapinarof cream 1% was effective and generally safe for up to 52 weeks of treatment in Japanese patients with AD.