Eric Simpson, MD, Discusses Recently Announced EADV Data On Tapinarof Cream for AD Down to 2 Years

Dermavant Sciences announced today new pruritus data for tapinarof (VTAMA) cream 1% from its phase 3 trials, ADORING 1 (NCT05014568) and ADORING 2 (NCT05032859), in adults and children down to 2 years of age with moderate to severe atopic dermatitis at the European Academy of Dermatology and Venereology (EADV) Congress in Berlin, Germany.¹

New data tapinarof cream data regarding pruritus relief includes:

• Greater reductions in Peak Pruritus-Numeric Rating Scale (PP-NRS) scores (mean) for tapinarof versus vehicle were observed as early as day 1, 24 hours after initial application, in ADORING 1 (–1.2 vs –0.9) and day 2 in ADORING 2 (–1.6 vs –1.4)
• Improvements in daily PP-NRS scores with tapinarof versus vehicle continued through the first 2 weeks and through week 8 of both trials
• Achieved highly statistically significant and clinically meaningful reductions in mean weekly PP-NRS scores as early as week 1, the first visit, for patients treated with tapinarof compared with vehicle (–2.0 vs –1.2 [P<0.0001]) and (–2.0 vs –1.3 [P=0.0010]), in ADORING 1 and ADORING 2, respectively
• Greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P<0.0001]), in both ADORING 1 and ADORING 2

ADORING 1 (n=407) and ADORING 2 (n=406), were 2 identical, double-blind, vehicle-controlled trials in which patients were randomized 2:1 to receive tapinarof cream 1% or vehicle once daily for 8 weeks. Patients with a Validated Investigator Global Assessment for Atopic Dermatitis score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5% to 35% were included in the trials. The efficacy endpoints that evaluated itch relief included mean changes in PP-NRS score (daily and by visit [weeks 1, 2, 4, and 8]) from baseline through week 8. The PP-NRS considers a patient’s worst itch over the past 24 hours and was assessed on an 11-point scale, in which 0 represents “no itch” and 10 represents their “worst imaginable itch.”

According to the announcement, “The new data being presented at EADV 2023 contains daily recorded PP-NRS scores of patients in ADORING 1 and ADORING 2 on VTAMA cream for the first time.” Patients or caregivers of patients recorded their PP-NRS scores daily. At baseline, mean overall PP-NRS scores were 6.7 and 6.8 in ADORING 1 and ADORING 2, respectively.

In an interview with Dermatology Times, Eric Simpson, MD, MCR, the Frances J. Storrs Medical dermatology professor and director of the CLEAR Eczema Center at the Oregon Health & Sciences University, further elaborated on the significance of tapinarof’s new atopic dermatitis data presented at EADV.

Eric Simpson, MD, MCR

Dermatology Times: What is the significance of the rapid onset of pruritus reduction within 24 hours after applying tapinarof cream, and how does this compare to existing treatments for atopic dermatitis?

Simpson: Itch remains the most burdensome symptom of atopic dermatitis, negatively impacting the quality of life of not only the patients, but also their families. This finding is consistent across age groups, countries, languages, and cultures in atopic dermatitis. There is a need for a topical option for these patients, particularly the pediatric population, that can provide rapid reduction in itch with sustained efficacy. Topical therapies are the cornerstone of eczema treatment. These new results showed rapid reduction in itch, as early as day 1 in ADORING 1 and day 2 in ADORING 2 alleviating the key symptom from the first application. While there are no head-to-head studies that compare tapinarof to other treatments, I’m confident in tapinarof’s potential if approved— as a novel, steroid-free topical therapy — to become an innovative treatment option that may benefit adults and children as young as two years old with atopic dermatitis.

Dermatology Times: How do these findings change the current treatment landscape for atopic dermatitis in both adults and children as young as 2 years old?

Simpson: Topical therapies for atopic dermatitis remain an area of unmet medical need, particularly in children. People with atopic dermatitis, and their caregivers, are often in search of topical, non-steroidal options that are safe and offer long-lasting relief. I’m thrilled by these findings which highlight the potential of tapinarof to be a therapeutic option with the ability to reduce itch for adults and children as young as 2 years old with atopic dermatitis. Caregivers are often reluctant to use topical steroids or nonsteroidal immunosuppressants that carry a boxed warning, so to be able to use a novel treatment with the convenience of once-daily dosing with safety down to two years of age will be welcomed by caregivers far and wide.

Dermatology Times: Can you provide insights into the differences, if any, between tapinarof cream's effectiveness in atopic dermatitis and plaque psoriasis, given its success in both conditions?

Simpson: The collective results from the psoriasis and atopic dermatitis clinical programs are encouraging for the communities in need of innovative options to treat their chronic skin conditions. These are such disparate conditions clinically, and I am hesitant to compare. However, the results are quite comparable with significant proportions of patients achieving clear skin in both disease states. In the psoriasis trials, some patients, once clear with tapinarof, enjoyed a prolonged period of clear skin without needing additional treatment. It will be interesting to see if this effect is seen in AD patients.

Dermatology Times: What are the potential implications of the anticipated sNDA filing for tapinarof in atopic dermatitis with the FDA in Q1 2024 for patients and dermatology clinicians?

Simpson: Typical treatment for children with atopic dermatitis includes topical steroids, topical calcineurin inhibitors, and oral and injectable systemic therapies. Topical therapies for atopic dermatitis remain an area of unmet medical need, particularly in children – caregivers for children with atopic dermatitis often seek topical, non-steroidal options that are safe and offer long-lasting relief. Current topical treatment options may not be able to be used long-term, due to limitations in body surface area or due to significant burning. Some of these treatments, like topical steroids, if used over an extended period of time continuously, may have serious side effects. The potential approval of tapinarof could be a significant development in the treatment of atopic dermatitis. If approved, tapinarof could provide another much-needed treatment option for patients with atopic dermatitis, particularly those who seek a non-steroidal option. The once-daily dosing and cream formulation will greatly improve the most difficult challenge for adults and caregivers alike – adherence to the treatment program for this chronic disease.

Reference

1. Dermavant announces new positive pruritus data for VTAMA (tapinarof) cream, 1% in adults and children as young as two years old with atopic dermatitis at EADV Congress 2023. Dermavant. News release. October 12, 2023. Accessed October 12, 2023. https://www.dermavant.com/dermavant-announces-new-positive-pruritus-data-for-vtamatapinarof-cream-1-in-adults-and-children-as-young-as-two-years-old-with-atopic-dermatitis-at-the-eadv-congress-2023/