Tapinarof on course to become a new topical treatment in AD

In phase 3, tapinarof cream demonstrated promising results as a future treatment option for adults as well as young children with atopic dermatitis (AD). The primary endpoint of clear or almost clear skin in the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) was achieved by 45% of participants at week 8 in the ADORING 1 and 2 trials.

“Topical therapy is the mainstay of therapy for all disease severity groups, and while we use topical corticosteroids as a first line because they are cheap and accessible, there are certainly a lot of limitations, especially for sensitive skin areas. So, we have unmet needs for new and better non-steroidal topical therapies,” Dr Jonathan Silverberg (George Washington University, Washington DC, USA) explained [1].

The aryl hydrocarbon receptor modulator tapinarof, which is already FDA-approved for psoriasis, is also in assessment for AD. Tapinarof “binds to and activates our aryl hydrocarbon receptor to downregulate proinflammatory cytokines associated with both AD as well as psoriasis, and it also has been shown to normalise skin barrier through upregulation of skin barrier proteins and reducing oxidative stress,” Dr Silverberg described tapinarof’s mode of action.

Dr Silverberg presented the identical phase 3 trials ADORING 1 (NCT05014568) and 2 (NCT05032859), which together included 813 adult and paediatric participants aged 2 years or older. The mean age of the participants was about 16 years with over 20% in the age group 2–6 years. Most participants (83.7–90.4%) had moderate disease (i.e. vIGA-AD 3), and all others had vIGA-AD 4. The participants were treated over 8 weeks with either once daily tapinarof cream 1% or a vehicle cream.

After 2 months, significantly higher proportions of participants in the tapinarof arms in both studies reached the primary endpoint of 0/1 in vIGA-AD: 45.4% and 46.4% compared with 13.9% and 18.0% on placebo (P<0.0001 for both comparisons). Similarly, the results for the secondary endpoint of EASI75 in ADORING 1 and 2 were 55.8% versus 22.9% (P<0.0001) and 59.1% versus 21.2% (P<0.0001), respectively. In addition, a ≥4-point decrease on the Peak Pruritus Numerical Rating Scale (PP-NRS) was detected in favour of tapinarof in both trials: 55.8% versus 34.2% (P=0.0366) and 52.8% versus 24.1% (P=0.0015).

The most common adverse events were folliculitis, headache, and nasopharyngitis with a rate of ≥5%. Dr Silverberg described the study drug as overall well-tolerated with a predictable safety profile, also referring to existing experience from the already FDA-approved indication for psoriasis.

“The take-home message is that tapinarof is a novel non-steroidal topical medication that has the potential to be used for the treatment of atopic dermatitis in patients down to 2 years without restrictions on duration, extent, or sites of application,” Dr Silverberg concluded.

1. 
   
   1. Silverberg J. Tapinarof cream 1% once daily: significant efficacy in the treatment of moderate to severe atopic dermatitis in two pivotal phase 3 trials in adults and children down to 2 years of age. D1T01.1G, EADV Congress 2023, 11–14 October, Berlin, Germany.

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Posted on 28 November, 202328 November, 2023