Tapinarof Cream 1% Once Daily for Plaque Psoriasis in Two Pivotal Phase 3 Trials: Minimal Systemic Exposure is Consistent With Adverse Event Profile

Background: Tapinarof cream 1% once daily (QD) demonstrated significant efficacy and was well tolerated in adults with mild to severe plaque psoriasis in PSOARING 1 and 2, two 12-week, vehicle- controlled, pivotal, phase 3 trials, and ∼4 months’ remittive effect off therapy in the long-term extension trial. In a phase 2a trial in patients with extensive psoriasis, application of tapinarof cream 1% QD under maximal-use conditions resulted in minimal systemic exposure. Here, we report pharmacokinetics from PSOARING 1 and 2. Tapinarof plasma concentrations were measured using a highly sensitive assay (quantifiable limit 50 picogram [pg, 10-12 g]/mL). Relationships were assessed between plasma concentrations and demographics and disease characteristics. For all tapinarof-treated patients, 96% of Week 4 samples and 97% at Week 12 were below the quantifiable assay limit. Mean tapinarof plasma concentrations were 8.6 pg/mL and 2.4 pg/mL at Week 4, and 9.9 pg/mL and 4.6 pg/mL at Week 12, in PSOARING 1 and 2, respectively. There were no differences in tapinarof plasma concentrations based on age, sex, race, and percent body surface area affected. Rates of systemic AEs were low and similar for tapinarof and vehicle: nasopharyngitis (tapinarof 5.7% vs vehicle 4.4%), headache (3.4% vs 1.2%), and upper respiratory tract infection (2.5% vs 3.5%). Topical application of tapinarof in patients with plaque psoriasis resulted in minimal systemic exposure. This favorable tapinarof pharmacokinetic profile is consistent with low rates of systemic AEs, lack of drug–drug interactions, and absence of QT-interval effects observed in trials, and indicates no requirement for dose adjustments.