Skin Clearance, Duration of Treatment-free Interval, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Abstract

Introduction: In ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA^®, Dermavant Sciences, an Organon Company) once daily (QD) demonstrated superior efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability from ADORING 3. Methods: Patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet ADORING 1 or 2 inclusion criteria, received tapinarof cream 1% QD for up to 48 weeks. Endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™]=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Patients entering with vIGA-AD™≥1 received tapinarof until vIGA-AD™=0. Those entering with or achieving vIGA-AD™=0 discontinued tapinarof and were assessed for maintenance of vIGA-AD™=0 or 1 (treatment-free interval). Patients with vIGA-AD™≥2 were re-treated until vIGA-AD™=0. Results: 728 patients enrolled; 83.0% pediatric (2–17 years). Overall, 51.9% entered with or achieved vIGA-AD™=0, and 81.6% entered with or achieved vIGA-AD™=0 or 1 at least once during ADORING 3. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent treatment-emergent adverse events (TEAEs) were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Trial discontinuations due to TEAEs were low (2.6%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated, even on sensitive skin. Conclusions: Tapinarof cream monotherapy was well tolerated and demonstrated high rates of complete disease clearance (51.9%) in patients down to age 2 years with AD. After discontinuing tapinarof, clear or almost clear skin was maintained for 79.8 consecutive days. No new safety signals and low rates of trial discontinuation were observed.