In this interview with the HCPLive editorial team, Eric Simpson, MD, MCR, spoke about the latest data from the ADORING 1 and ADORING 2 phase 3 trials, announced by Dermavant and presented at the the 2023 European Academy of Dermatology and Venereology (EADV) Congress in Berlin this week.¹

The new data, some of which was previously covered by HCPLive, contained the daily recorded PP-NRS scores of study participants being treated, and this was available for the first time.²

Simpson was the study author, and is known for his work as professor of dermatology at the School of Medicine at Oregon Health & Science University. He discussed the new findings from EADV which indicated a rapid reduction in pruritus as early as 24 hours following the initial application of tapinarof, 1% (VTAMA) cream for adults and children.

HCPLive: Can you provide an overview of the key findings from the ADORING 1 and ADORING 2 studies that were presented at EADV and their significance in the treatment of atopic dermatitis?

Simpson: The new results presented at EADV show a rapid reduction in itch as early as 24 hours after the first application of tapinarof, with consistent improvement in itch through week 8. In these studies, itch relief was measured by mean changes in PP-NRS scores (daily and by visit on weeks 1, 2, 4 and 8) from baseline through week 8. The results are as follows:

• For daily evaluations of itch from baseline, greater reductions in PP-NRS mean scores for VTAMA cream versus vehicle were observed as early as day 1 in ADORING 1 (-1.2 vs -0.9) and day 2 in ADORING 2 (-1.6 vs -1.4).
• Tapinarof achieved statistically significant and clinically meaningful reductions in mean weekly PP-NRS scores as early as week 1 compared with vehicle in ADORING 1 (-2.0 vs -1.2 [P<0.0001]) and ADORING 2 (-2.0 vs -1.3 [P=0.001]).
• Greater reductions in mean PP-NRS scores with VTAMA cream versus vehicle were seen for all visits through week 8 in ADORING 1 (-4.1 vs -2.6 [P<0.0001]) and ADORING 2 (-4.1 vs -2.4 [P<0.0001]).

Itch remains the most burdensome and prevalent symptom of atopic dermatitis, and these results highlight the potential of tapinarof as a clinically meaningful therapy with the ability to reduce itch for adults and children living with atopic dermatitis. Data from Matthias Augustin highlights the importance of itch and speed of response, where almost all patients wanted to be free of itching with rapid healing of skin.

HCPLive: The rapid onset of pruritus (itch) reduction within 24 hours is a remarkable finding. Can you explain the mechanisms behind tapinarof cream that contribute to such quick relief for patients with atopic dermatitis?

Simpson: I am thrilled by these results showing rapid reduction in itch as early as 24 hours after the first tapinarof application. Tapinarof is an agonist of aryl hydrocarbon receptor, which plays an important role in balancing homeostasis in the skin. The specific mechanisms by which tapinarof exerts its therapeutic action in atopic dermatitis is unknown but are thought to include antioxidant, barrier repair, and anti-inflammatory mechanisms. I am very curious as to whether there are direct effects of this therapy on sensory nerves by as of yet unknown mechanisms, or whether this is cytokine suppression via anti-inflammatory effects, or something else entirely.

HCPLive: The PP-NRS mean scores showed greater reductions with tapinarof cream compared to the vehicle. What do these scores reveal about the effectiveness of tapinarof cream, and how does this impact patient quality of life?

Simpson: Itch remains the most burdensome and prevalent symptom of atopic dermatitis, negatively impacting the quality of life of, not only for the patients but also their families. Itch often impacts sleep that can have significant detrimental impacts on mood in adults and possibly growth and development in kids. There remains a need for a topical option for these patients, particularly the pediatric population, that can provide rapid reduction in itch with sustained efficacy. By providing rapid relief, caregivers and older patients with AD get immediate positive feedback which encourages them to remain adherent to their topical therapy.

HCPLive: It's impressive that improvements in itch with tapinarof cream continued through Week 8 in both ADORING 1 and ADORING 2. Could you elaborate on the durability of these improvements and whether any side effects or tolerability issues were observed during the study?

Simpson: These new results showed consistent improvements in itch with tapinarof through week 8. I look forward to learning more about the long-term outcomes, including itch relief of tapinarof in the ADORING 3 study. In psoriasis, some patients experienced prolonged clearing once tapinarof was discontinued. We will be certainly evaluating this in AD.

As previously reported earlier this year, tapinarof showed no new safety or tolerability signals in ADORING 1 and ADORING 2, including in children as young as 2 years old. Adverse events were mostly mild to moderate with a low study discontinuation rate due to adverse events (ADORING 1: 1.9% VTAMA vs. 3.6% vehicle; ADORING 2: 1.5% VTAMA vs. 3.0% vehicle). Adverse events of special interest included contact dermatitis (ADORING 1: 1.5% VTAMA vs. 2.2% vehicle; ADORING 2: 1.1% VTAMA vs. 1.5% vehicle) and follicular event (ADORING 1: 10.0% VTAMA vs. 0.7% vehicle; ADORING 2: 8.9% VTAMA vs. 1.5% vehicle).

HCPLive: Tapinarof cream became the #1 prescribed branded topical treatment for adults with plaque psoriasis in 2022. How do the findings from the ADORING 1 and ADORING 2 studies extend the potential applications of tapinarof cream, and what could this mean for the field of dermatology?

Simpson: The collective results from ADORING 1 and 2 underscore the potential of tapinarof to be an important non-steroidal, topical treatment option for not only adults and children with atopic dermatitis but also the physicians treating them. Tapinarof has already brought about change to the plaque psoriasis treatment paradigm. I think tapinarof cream may potentially evolve and simplify the treatment landscape in AD, given that nonsteroidal options that can meet patients’ expectations for safety, efficacy, and tolerability are sorely needed in this space. Interestingly, tapinarof may be positioned to be a potential two-in-one first-line topical treatment for both atopic dermatitis and plaque psoriasis which currently does not exist outside of topical steroids.

HCPLive: Atopic dermatitis can affect both adults and children,. Can you discuss the implications of the study findings for pediatric patients and how tapinarof cream may change the treatment landscape for this younger demographic?

Simpson: In the U.S., atopic dermatitis affects more than 9.6 million children, the majority of whom suffer from severe itching and scratching. Safe and effective topical therapies for atopic dermatitis remain an area of unmet medical need, particularly in children. Parents of children with atopic dermatitis are often in search of non-steroidal topical options that are safe and offer sustained relief. Further, some non-steroidal have either boxed warnings or are limited by burning upon application. If approved, tapinarof could provide a much-needed treatment option for parents of children – particularly toddlers as young as 2 years old –with atopic dermatitis, particularly those who seek a non-steroidal option.

HCPLive: Patients with atopic dermatitis often face a range of challenges, including itch, discomfort, and compromised quality of life. How does the efficacy of tapinarof cream in providing rapid itch reduction address some of these challenges and improve the overall well-being of patients?

Simpson: The majority of patients diagnosed with atopic dermatitis suffer from severe itching and scratching resulting in skin inflammation and damage to the skin barrier. Beyond physical effects, itch can have negative impacts on quality of life for patients and their families, as symptoms tend to worsen at night, disturbing sleep and causing fatigue, which in children may lead to inattention in school. In adults, sleep disturbance has been linked to mood disorders.

Building upon the topline results from ADORING 1 and 2, these new findings suggest tapinarof has the potential to advance the treatment landscape for adults and children with atopic dermatitis through improved disease control and symptom reduction capabilities that will likely improve sleep over time. This of course would need to be confirmed in longer studies with appropriate outcomes.

HCPLive: Looking ahead, what are the next steps and future research directions for tapinarof cream in the context of atopic dermatitis treatment? Are there any plans for additional studies or clinical trials to further explore its potential benefits?

Simpson: I look forward to seeing long-term efficacy and safety results of tapinarof in atopic dermatitis from ADORING 3 study and whether some patients can experience a prolonged period of clearance off of therapy in AD as was seen in psoriasis.

References

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 the EADV Congress 2023. Dermavant. October 12, 2023. Date accessed: October 12, 2023. https://www.biospace.com/article/releases/dermavant-announces-new-positive-pruritus-data-for-vtama-tapinarof-cream-1-percent-in-adults-and-children-as-young-as-two-years-old-with-atopic-dermatitis-at-the-eadv-congress-2023/.}
2. ^{Smith T. Adelaide Hebert, MD: Positive Phase 3 Data on Tapinarof for Atopic Dermatitis Patients. HCPLive. May 17, 2023. Date accessed: October 12, 2023. https://www.hcplive.com/view/adelaide-hebert-positive-phase-3-data-tapinarof-atopic-dermatitis-patients.}