Dermal Safety of Tapinarof Cream 1%: Results From 4 Phase 1 Trials

Abstract

Background: Tapinarof (VTAMA ® ; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application. Objective: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions. Methods: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity. Results: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials. Conclusions: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults.

Management of Plaque Psoriasis in Adults: Clinical Utility of Tapinarof Cream

“…Four phase I controlled trials were conducted which assessed for the cumulative skin irritation, sensitization, photosensitization, and phototoxicity potential of tapinarof 1% cream. 30 Tapinarof was compared to vehicle, 0.2% sodium lauryl sulfate (SLS, positive control), and 0.9% saline (negative control). These trials included a total of 376 participants, the majority of which had Fitzpatrick skin types III–V.…”

“…These trials included a total of 376 participants, the majority of which had Fitzpatrick skin types III–V. 30 The mean irritation score was 0.92 for tapinarof 1% cream (n = 45) versus 0.02 for vehicle, 0.1 for 0.9% saline, and 2.45 for SLS [ P = <0.0001 for all comparisons]. 30 Based on tapinarof’s normalized total irritation score (193/630), it was classified as having a slight potential for very mild cumulative irritation.…”

“… 30 Based on tapinarof’s normalized total irritation score (193/630), it was classified as having a slight potential for very mild cumulative irritation. 30 Of the patients assessed for skin sensitization (n = 240), no reactions were classified as indicative of sensitization to tapinarof cream, including 38.7% of the patients experiencing minimal, barely perceptible erythema (maximum sensitization score 1), 1.7% experiencing definite erythema and minimal edema/papulation (maximum sensitization score 2), and 0.4% experiencing definite erythema, edema, papules and/or a strong reaction spreading beyond test site (maximum sensitization score 3). 30 Fifty-eight patients were assessed for photoallergy, of which the maximum photosensitization score observed was a score of 1 (mild erythema/edema) for both irradiated and non-irradiated sites treated with tapinarof 1% cream or vehicle.…”

Tapinarof for psoriasis and atopic dermatitis: 15 years of clinical research

“…It is important to note that no cases of allergic contact dermatitis were observed in more than 200 healthy subjects who had tapinarof applied repetitively under occlusion in the typical irritation/sensitization study required by regulatory authorities for the approval of a topical drug. 22 The dermatitis does not appear to be irritant contact dermatitis, as tapinarof's tolerance on sensitive area has also been studied in phase 3 and it was very well tolerated when applied on the face, genitals and skin folds. 19 The pathophysiology of tapinarof-induced dermatitis is unknown but, in some patients, it is reminiscent of the dermatitis sometimes seen in psoriasis patients treated with anti-IL-17 antibodies.…”

“…In some patients the dermatitis is more intense, with significant oedema, sometimes oozing, suggesting an allergic contact dermatitis. It is important to note that no cases of allergic contact dermatitis were observed in more than 200 healthy subjects who had tapinarof applied repetitively under occlusion in the typical irritation/sensitization study required by regulatory authorities for the approval of a topical drug 22 . The dermatitis does not appear to be irritant contact dermatitis, as tapinarof's tolerance on sensitive area has also been studied in phase 3 and it was very well tolerated when applied on the face, genitals and skin folds 19 .…”