Tapinarof Cream 1% for Extensive Plaque Psoriasis: A Maximal Use Trial on Safety, Tolerability, and Pharmacokinetics

Abstract

Background Tapinarof is a novel topical therapeutic aryl hydrocarbon receptor modulating agent in development for the treatment of psoriasis and atopic dermatitis. Objective This multicenter, open-label trial assessed the safety, tolerability, pharmacokinetics (PK), and efficacy of tapinarof cream 1% once daily (QD) under maximal use conditions in extensive plaque psoriasis. Methods Adults with a baseline Physician Global Assessment (PGA) score of ≥ 3 and body surface area (BSA) involvement ≥ 20% received tapinarof cream 1% QD for 29 days. Safety and tolerability assessments included adverse events (AEs) and local tolerability scales. PK parameters were calculated using non-compartmental analysis. Efficacy assessments included change in PGA, Psoriasis Area and Severity Index score, and %BSA affected. Results Twenty-one patients were enrolled. Common AEs were folliculitis, headache, back pain, and pruritus (none led to discontinuation). Tapinarof plasma exposure was low, with the majority of concentrations being below detectable limits. At day 29, 14 patients (73.7%) had a ≥ 1-grade improvement in PGA score and six patients (31.6%) had a ≥ 2-grade improvement; four patients (21.1%) achieved treatment success (PGA 0 or 1 and ≥ 2-grade improvement). Conclusion Tapinarof cream 1% QD was well tolerated, with limited systemic exposure and significant efficacy at 4 weeks in patients with extensive plaque psoriasis. ClinicalTrials.gov Identifier NCT04042103. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00641-4.

Tapinarof Cream 1%: First Approval

“…Consistent with its pharmacokinetic profile and minimal systemic exposure (Sect. 2.2 ), no evidence of clinically relevant QTc interval prolongation has been observed either when tapinarof cream 1% is used at the approved recommended dosage [ 7 ] or under maximal use conditions in adults with a body surface area (BSA) involvement ≥ 20% [ 19 ].…”

“…Following topical application of tapinarof cream 1%, tapinarof is absorbed into the skin; however after once-daily applications, the plasma concentration of tapinarof was below the quantifiable limits in 68% of pharmacokinetic samples in a sensitive assay (lower limit of quantification of the assay was 50 pg/mL) in a maximal use trial [ 7 , 19 ]. The tapinarof mean C max was 0.9 ng/mL and mean AUC 0–last was 4.1 ng·h/mL on day 1 after application of a mean daily dose of 5.23 g to a mean BSA involvement of 27.2% (range 20.5–46.0%) in patients ( n = 21) with extensive plaque psoriasis.…”

“…The tapinarof mean C max was 0.9 ng/mL and mean AUC 0–last was 4.1 ng·h/mL on day 1 after application of a mean daily dose of 5.23 g to a mean BSA involvement of 27.2% (range 20.5–46.0%) in patients ( n = 21) with extensive plaque psoriasis. T max occurred 2–5 h after application [ 7 , 19 ]. No accumulation was evident after repeated topical application; on day 29 the mean C max was 0.12 ng/mL and AUC 0–last was 0.61 ng·h/mL [ 7 , 19 ].…”

“…T max occurred 2–5 h after application [ 7 , 19 ]. No accumulation was evident after repeated topical application; on day 29 the mean C max was 0.12 ng/mL and AUC 0–last was 0.61 ng·h/mL [ 7 , 19 ]. These results indicate minimal systemic exposure to tapinarof following topical application under conditions of maximal use.…”

“…Tapinarof cream 1% applied to affected skin once daily significantly reduced the severity of plaque psoriasis in a 29-day phase 2a maximal use trial (NCT04042103) in patients with extensive plaque psoriasis (mean BSA affected at baseline was 27.2%) [ 19 ]. At baseline, 12 of the 19 patients who completed the study had a PGA score of 3 and the remaining 7 patients had a PGA score of 4; by day 29 of treatment, only 5 patients had a PGA score of 3 and 1 patient had a PGA score of 4.…”