Tapinarof Cream, 1%, Gets FDA Green Light for Atopic Dermatitis in Individuals Aged 2 Years and Older

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Tapinarof cream, 1%, received FDA approval today for the treatment of atopic dermatitis in individuals aged 2 years and older, according to sponsor company Organon. Approval follows submission of a supplemental new drug application (sNDA) to the regulator in late April this year and comes 3 months ahead of the agency’s extended target action date of March 12, 2025.¹

The FDA’s decision is supported by positive data from the phase 3 ADORING 1 and 2 studies, identical double-blind, randomized vehicle-controlled trials; an open-label maximal usage pharmacokinetics trial in children aged 2 to 17 years; and the interim analysis of ADORING 3, a phase 3, 48-week, open-label, extension trial.

“With the FDA’s approval of VTAMA cream in atopic dermatitis for adults and children as young as 2 years old, there is now a therapy that offers the potential for powerful skin clearance with no label warnings or precautions, contraindications, and no restrictions on duration of use or percentage of body surface area affected,” Kevin Ali, Organon chief executive officer, said in the company news release.¹

ADORING 1 and 2

The ADORING 1 and ADORING 2 twin trials evaluated the efficacy and safety of tapinarof cream, 1%, in adults and children as young as 2 years old with moderate to severe AD. Study participants had a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 (moderate) to 4 (severe) at baseline. In both studies investigators reported a statistically significant difference compared with vehicle treatmentin the proportion of participants that achieved score of clear (0) or almost clear (1) and a minimum 2-grade improvement from baseline at week 8 on the vIGA-AD.

The endpoints were achieved by close to half of participants in each study, ie, in ADORING 1 by 45.4% and in ADORING 2 by 46.4% compared with 18% of participants treated with vehicle (P <.001). Tapinarof-treated participants also experienced at least a 75% improvement in scores on the Eczema Area and Severity Index and a 4 point or greater improvement in Peak Pruritus Numerical Rating Scale for participants aged 12 years and older. Itch relief was rapid, with participants and caregivers reporting improvement as early as 24 hours after the first application.

ADORING 3

ADORING 3 was a 48-week open-label, long-term extension (LTE) study and enrolled participants from the ADORING 1 and 2 trials, the 4-week maximal usage pharmacokinetics study, and tapinarof cream-naive children aged 2 to 17 years with either mild, moderate or severe AD that did not meet inclusion in the earlier studies.

Of the final 728 ADORING 3 LTE participants, 83% were aged 2 to 17 years. Slightly more than one-half (51.9%) entered with complete disease clearance or achieved that status at least once during the 48 weeks. Among those 378 participants, the average length of the first treatment-free interval was approximately 80 consecutive days—or, nearly 3 months. For any participant whose condition returned to a vIGA-AD score of 2 or higher, tapinarof treatment was reintroduced until they achieved complete disease clearance again or the study concluded. Researchers reported that the tapinarof safety profile with long-term use in ADORING 3 was consistent with the profile seen at week 8.

The most common adverse events, observed in at least 1% or participants, included upper respiratory tract infection, folliculitis, lower respiratory tract infection, headache, asthma, vomiting, ear infection, pain in extremities, and abdominal discomfort.

The Future for Nonsteroidal Topicals

“Nonsteroidal topicals, like [tapinarof] cream, have really challenged the treatment paradigm and I have seen a shift in my personal dermatology practice where I reach for [tapinarof] over topical corticosteroids,” Mona Shahriari, MD, assistant clinical professor of dermatology at the Yale School of Medicine, in New Haven, CT said in an interview with Patient Care earlier this year. Shahriari, who is also associate director of clinical trials at Central Connecticut Dermatology Research, added, “As someone who sees the physical and emotional impact that chronic skin conditions can have on patients daily, I’m excited about the innovations we’re witnessing within the topical treatment landscape.

Tapinarof cream is a novel, aryl hydrocarbon receptor agonist originally approved in May 2022 as the first non-steroidal, topical novel chemical entity available to treat psoriasis in the US in more than 25 years. Tapinarof is indicated for mild, moderate, and severe plaque psoriasis with no label warnings or precautions, contraindications, restrictions on duration of use, or percentage of body surface area affected.