Efficacy and safety of benvitimod 1% cream for atopic dermatitis in patients aged 2 years and older: A phase III randomized clinical trial

Abstract Background: Benvitimod (tapinarof), an aryl hydrocarbon receptor (AhR) agonist approved for treating plaque psoriasis, is being investigated as a potential treatment for atopic dermatitis (AD). The aim of this study was to evaluate the efficacy and safety of benvitimod 1% cream in patients aged 2 years or older with AD. Methods: This randomized controlled trial enrolled 271 Chinese patients with AD aged ≥2 years, who received either benvitimod 1% cream ( n = 183) or vehicle cream ( n = 88) twice daily for 8 weeks in a 2:1 ratio at 35 sites in China from June to November 2023. The primary endpoint was the proportion of patients achieving a 75% improvement in the Eczema Area and Severity Index (EASI) 75 at week 8. Secondary endpoints included achievement of Investigator’s Global Assessment (IGA) scores of 0/1, 90% EASI improvement (EASI 90), and ≥3-point reduction in Peak Pruritus Numerical Rating Scale (PP-NRS). Treatment-emergent adverse events (TEAEs) were monitored for safety evaluation. Furthermore, a subset of patients ( n = 43) opted into a 44-week open-label extension. Results: At week 8, a significantly higher proportion of patients treated with benvitimod achieved EASI 75 compared to those receiving vehicle (54.4% [ n = 183] vs. 25.5% [ n = 88]; P <0.001). The benvitimod group also showed superior results across all secondary endpoints: IGA 0/1 (46.2% [ n = 183] vs . 21.4% [ n = 88]; P <0.001), EASI 90 (33.9% [58/171] vs . 13.5% [10/74]; P <0.001), and ≥3-point decrease in PP-NRS (54.0% [47/87] vs . 27.9% [12/43]; P <0.01). TEAEs occurred in 51.4% (94/183) of benvitimod-treated patients vs. 43.2% (38/88) of vehicle-treated patients, with most events being mild to moderate in severity. Conclusion: Benvitimod 1% cream demonstrated favorable efficacy and safety in adult and pediatric patients with AD, supporting its potential as a novel topical treatment option. Trial Registration: chinadrugtrials.org.cn, CTR20231413.