Topical non-steroidal cream approved by FDA for atopic dermatitis

Tapinarof 1% cream (Vtama) has been approved by the Food and Drug Administration (FDA) for the treatment of atopic dermatitis (AD, eczema) in adults and children of two years and older.  Vtama was approved in the USA for treatment of plaque psoriasis in 2022.

Tapinarof is an aryl hydrocarbon receptor (AhR) agonist. It reduces inflammation and normalises skin barrier function by ligand-dependent activation of AhR, resulting in downregulation of inflammatory Th2 cytokines implicated in AD, modulation of keratinocyte differentiation and increased expression of skin-barrier components, including proteins (filaggrin, loricrin, hornerin, and involucrin) and ceramides.¹

The approval was supported by the pivotal ADORING 1 and ADORING 2 studies. These were double-blind, randomised, vehicle-controlled phase 3 trials (NCT05014568, NCT05032859), that assessed the efficacy and safety of tapinarof cream 1%, once daily, in adults and children of two years of age and older with AD.

The results of the eight-week trials showed that significantly higher proportions of patients achieved the efficacy endpoint (a score of 0 or 1 (clear or almost clear) on the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), along with at least a 2-grade improvement from baseline to week 8).

• ADORING 1: 45.4% with tapinarof vs 13.9% with vehicle (P < .0001)
• ADORING 2: 46.4% with tapinarof vs 18% with vehicle (P < .0001)

Significant improvements were also reported in the secondary endpoints – Eczema Area and Severity Index (EASI) score and the Peak Pruritus Numerical Rating Scale (PP-NRS).  Notably, patients and caregivers reported itch improvement as early as 24 hours after first application of Vtama cream.

Safety

Common treatment-emergent adverse events (TEAEs) (≥5% in any arm) were folliculitis, headache, and nasopharyngitis. Most TEAEs were mild or moderate and were associated with low discontinuation rates. There were few serious TEAEs and none were considered treatment related. Trial discontinuation due to AEs was more frequent in the vehicle arms than with tapinarof.

It is of interest that studies show minimal-to-no systemic absorption tapinarof from the cream under maximal usage conditions, including in children down to two years of age with extensive AD, and in adults with plaque psoriasis and extensive disease.¹

ADORING 3 – Long-term evaluation

ADORING 3, a 48-week open-label, LTE study, enrolled eligible patients from ADORING 1, ADORING 2, and other suitable patients who did not meet pivotal studies’ inclusion criteria.

In ADORING 3, patients (N=728) were followed for up to 48 weeks, with safety and efficacy endpoints that included the achievement of complete disease clearance (vIGA-AD=0), and the achievement of clear or almost clear skin (vIGA-AD=0 or 1). Patients entering with any disease activity (vIGA-AD≥1) were treated with Vtama cream, 1% until complete disease clearance was achieved (vIGA-AD=0) or study completion. For the 378 patients who entered with or achieved complete disease clearance (vIGA-AD=0) in ADORING 3 and discontinued treatment with Vtama cream, the mean duration of the first period of remission was approximately 80 consecutive days. Patients whose AD returned to mild or above (vIGA-AD≥2) were re-treated with VTAMA cream until complete disease clearance was achieved again or study completion. The safety profile with long term use was generally consistent with the safety profile observed at Week 8.

Itch-relief

“Vtama cream approval in AD is important because it can be prescribed for children as young as 2 years old. Vtama cream has the potential to bring much needed relief to a significant number of children suffering from this disease,” said Adelaide A. Hebert, MD, Professor and Chief of Paediatric Dermatology at McGovern Medical School at UT Health Houston and Children’s Memorial Hermann Hospital and lead investigator for the ADORING program. “Moreover, because the prevalence of itch makes this condition extremely burdensome to patients and their families, the itch data from the ADORING program demonstrates reduction of one of the condition’s most prevalent symptoms with use of Vtama cream.”

Take home message

In these 8-week trials, tapinarof cream 1%, once daily was superior to vehicle in the treatment of AD in adults and children. Tapinarof potentially fills a gap in the treatment armamentarium for a highly effective, nonsteroidal topical treatment that can be used down to two years of age without restrictions on the severity of disease, duration of use, total body surface area treated, or sites of application.¹

Reference

1. Silverberg J, Eichenfield LF, Hebert AA et al. Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials. J Am Acad Dermatol. 2024; 94: 457-465