This is an open-label, multi-center study to evaluate the efficacy and safety of VTAMA (tapinarof) cream, 1% in adults with plaque psoriasis occurring in the head and neck region

BACKGROUND:

Tapinarof cream is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for treatment of psoriasis and atopic dermatitis.

METHODS:

In a phase 2b, double-blind, vehicle-controlled study, adults with plaque psoriasis were randomized to tapinarof cream 0.5% or 1% once or twice daily or vehicle once or twice daily for 12 weeks with 4-week follow-up. Efficacy outcomes included Physician Global Assessment (PGA) scores, change in PGA and total target lesion grading scores, and proportion of patients achieving ≥50%, ≥75%, and ≥90% reductions in the Psoriasis Area and Severity Index scores from baseline (PASI50, PASI75, and PASI90).

RESULTS:

At week 12, improvements were observed in all tapinarof groups vs vehicle in PGA response, change in PGA and total target lesion grading scores, PASI50 (71%-92% vs 10%-32%), PASI75 (46%-65% vs 5%-16%), and PASI90 (18%-40% vs 0%); all differences were statistically significant with tapinarof 1% once daily. Tapinarof responses were apparent from week 2, with significant efficacy at week 8 maintained through week 16. Most adverse events were mild or moderate.

LIMITATIONS:

The analyses reported require confirmation in larger prospective studies.

CONCLUSIONS:

Tapinarof may represent an important advance in the development of topical medicines for treatment of psoriasis.

Background/Objective: Despite available options for treating psoriasis, there is a need for effective topical therapies that can be used without concerns about body surface area (BSA) restrictions or long treatment duration. Tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for the treatment of psoriasis and atopic dermatitis. Method: This Phase IIb, double-blind, six-arm, vehicle-controlled randomized study (NCT02564042) assessed the efficacy and safety of tapinarof cream in subjects with plaque psoriasis. Subjects (aged 18-65 years) with 1 to 15 percent BSA involvement and Physician Global Assessment (PGA) score of at least 2 at baseline were randomized 1:1:1:1:1:1 to tapinarof cream 0.5% or 1% once (QD) or twice daily (BID) or vehicle QD or BID for 12 weeks with a four-week follow-up. The primary end point was the proportion of subjects achieving PGA score 0 or 1 and 2-grade or greater improvement in PGA score from baseline to Week 12, which has been reported elsewhere. Secondary efficacy outcomes reported here include a 50-percent or greater reduction in Psoriasis Area and Severity Index (PASI50), PASI90, mean change in PGA scores and total target lesion grading scores from baseline, and pruritus numeric rating scale (NRS) response. Results: Of 227 randomized subjects, 174 completed the study. Most subjects (80%) had a baseline PGA score of 3 (moderate). Mean PASI was 8.8. Higher PASI50 (all p<0.001) and PASI90 (p<0.01 except for the tapinarof 0.5% QD group) response rates were observed in all tapinarof groups versus vehicle at Week 12 and were maintained for four weeks after the end of study treatment. Mean improvements in PGA scores (all p<0.001) and total target lesion grading scores (all p<0.001) from baseline to Week 12 were significantly greater in all tapinarof groups versus vehicle and were maintained for four weeks after the end of study treatment (all p<0.01). In subjects with a baseline pruritus NRS item score of 4 or greater, pruritus NRS response at Week 12 (≥4 improvement in pruritus NRS score from baseline) was 55 to 73 percent (tapinarof 1% groups) and 56 to 57 percent (tapinarof 0.5% groups) versus 33 to 60 percent (vehicle groups). Most treatment-emergent adverse events were mild or moderate, and the most common (≥5%) across all groups were folliculitis (9%) and contact dermatitis (5%). Most incidences of folliculitis and contact dermatitis were mild or moderate. Conclusion: These results support the primary analysis showing that tapinarof cream was efficacious and well tolerated in adults with psoriasis.1 A Phase III study of tapinarof cream 1% QD in psoriasis is ongoing (NCT03956355).

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist approved for the treatment of atopic dermatitis (AD) in Japanese patients aged ≥12 years. We evaluated the efficacy and safety of tapinarof in Japanese pediatric patients aged 2 to 11 years with AD in a phase 2, multicenter, randomized, double-blind, vehicle-controlled trial. Eligible patients (N = 121) were randomized 1:1:1 to receive tapinarof cream 0.5%, tapinarof cream 1%, or vehicle cream once daily for 8 weeks. At week 8, the least-squares mean percent change from baseline in Eczema Area and Severity Index (EASI) score (the primary endpoint) was −81.29% in the tapinarof 0.5% group, −77.62% in the tapinarof 1% group, and − 18.56% in the vehicle group. Reductions in EASI score at week 8 were significantly greater in the tapinarof groups than in the vehicle group (p < 0.0001 for both comparisons). The proportion of patients with ≥75% improvement from baseline in EASI score at week 8 was 77.5% in the tapinarof 0.5% group, 70.7% in the tapinarof 1% group, and 15.0% in the vehicle group. The proportion of patients who achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 was 32.5% in the tapinarof 0.5% group, 43.9% in the tapinarof 1% group, and 17.5% in the vehicle group. No treatment-related serious adverse events (AEs) were reported; all of the AEs were mild or moderate. Common AEs in tapinarof-treated patients included gastroenteritis, application site irritation, and nasopharyngitis. The incidence of trial discontinuations due to AEs was low in tapinarof-treated patients (one patient for each strength). In summary, both strengths of tapinarof cream demonstrated greater efficacy than vehicle cream and were well tolerated in Japanese pediatric patients with AD. © 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

BACKGROUND:

Tapinarof cream 1% once daily demonstrated significant efficacy versus vehicle and was well tolerated in two 12-week, phase 3 pivotal trials in adults with mild-to-severe plaque psoriasis.

OBJECTIVE:

To assess long-term, health-related quality of life and patient satisfaction with tapinarof.

METHODS:

Patients completing the 12-week trials were eligible for 40 weeks of open-label tapinarof based on Physician Global Assessment score in PSOARING 3, with a 4-week follow-up. Dermatology Life Quality Index was assessed at every visit; Patient Satisfaction Questionnaire responses were assessed at week 40 or early termination.

RESULTS:

Seven hundred sixty-three (91.6%) eligible patients enrolled; 78.5% completed the Patient Satisfaction Questionnaire. DLQI scores improved and were maintained. By week 40, 68.0% of patients had a DLQI of 0 or 1, indicating no impact of psoriasis on health-related quality of life. Most patients strongly agreed or agreed with all Patient Satisfaction Questionnaire questions assessing confidence in tapinarof and satisfaction with efficacy (62.9%-85.8%), application ease and cosmetic elegance (79.9%-96.3%), and preference for tapinarof versus prior psoriasis therapies (55.3%-81.7%).

LIMITATIONS:

Open-label; no control; may not be generalizable to all forms of psoriasis.

CONCLUSIONS:

Continued and durable improvements in health-related quality of life, high rates of patient satisfaction, and positive perceptions of tapinarof cream were demonstrated.

Background: Tapinarof cream 1% once daily (QD) demonstrated significant efficacy in patients down to age 2 years with atopic dermatitis (AD) in the ADORING 1 and 2 phase 3 trials. We report local tolerability outcomes. Methods: Patients received Tapinarof or vehicle cream QD for 8 weeks. Tolerability was evaluated using patient/parent/caregiver and investigator 5-point Local Tolerability Scales (LTS). Investigators assessed tolerability for sensitive skin areas, including face/neck. Results: 813 patients were randomized (∼80% pediatric). Mean pretreatment baseline overall LTS scores were similar across groups and trials: 1.0–1.9 (patient-assessed) indicating slight burning/stinging and itching; and 0.3–0.6 (investigator-assessed) indicating no-to-minimal irritation. Tapinarof was well tolerated with improvement from pretreatment baseline and no-to-minimal burning/stinging and itching from first application through Week 8 (patient-reported): mean Week 8 LTS scores were 0.2–0.4 (burning/stinging) and 0.6–0.8 (itching). Investigators reported improvement from pretreatment baseline with no-to-minimal irritation (dryness/erythema/peeling) from first Tapinarof application through Week 8 (mean LTS scores: 0.2 and 0.1 in ADORING 1 and 2, respectively). Across sensitive skin, investigators reported no-to-minimal irritation from first application through Week 8 (mean scores [Tapinarof versus vehicle]: 0–0.3 versus 0–1.0). Conclusion: Tapinarof was well tolerated locally from first application through Week 8, including on sensitive skin areas. Clinicaltrials.gov numbers NCT05014568, NCT05032859. © 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.

BACKGROUND:

Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment.

METHODS:

A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores.

RESULTS:

Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate.

LIMITATIONS:

Larger prospective studies are required to confirm the reported analyses.

CONCLUSIONS:

Tapinarof is a potential important advance in topical medicine development for AD.

Background: Tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy versus vehicle and was well‐tolerated in adults with mild to severe plaque psoriasis in PSOARING 1 and 2, two 12‐week, Phase 3 trials. In addition, significantly greater improvements in Dermatology Life Quality Index (DLQI) change from baseline at Week 12 were observed with tapinarof versus vehicle. Objective: To evaluate correlations between the DLQI and clinical efficacy as assessed by Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI) in PSOARING 1 and 2. Methods: Patients in PSOARING 1 and 2 were randomized to tapinarof or vehicle for 12 weeks. The DLQI is a 10‐item scale where each item is rated on a 4‐point scale from zero (not at all) to three (very much); lower scores indicate higher quality of life (QoL). Efficacy was evaluated using PGA and PASI. Spearman rank correlations evaluated correlations between changes in efficacy and QoL from baseline at Week 12. Analyses used observed cases and were based on the intention‐to‐treat population. Results: 683 tapinarof and 342 vehicle‐treated patients from PSOARING 1 and 2 were included in the analyses. At baseline, 79.2 to 83.9 percent of patients had a PGA of 3 (moderate), mean PASI of 8.9‐9.1, and mean DLQI of 8.2‐8.7 (moderate impact of disease on QoL) in PSOARING 1 and 2. Mean change in DLQI from baseline at Week 12 was ‐5.0 vs ‐3.0 (P<0.0001) and ‐4.7 vs. ‐1.6 (P<0.0001), with tapinarof versus vehicle in each trial, respectively. The minimal clinically important difference in DLQI of 4 was exceeded at Week 12 in the tapinarof groups. A significantly higher proportion of patients achieved a DLQI of 0 or 1 at Week 12 in the tapinarof groups versus vehicle: 47.4 percent vs 23.3 percent (P<0.0001) and 44.9 percent vs 16.1 percent (P<0.0001) in each trial, respectively; statistical significance in favor of tapinarof was observed as early as Week 4. Improvements in DLQI in the tapinarof groups at Week 12 were statistically correlated with improvements in PGA (0.28 and 0.29, P<0.0001) and PASI (0.28 and 0.40, P<0.0001) in each trial, respectively. Conclusion: Tapinarof demonstrated rapid, clinically meaningful, and statistically significant improvements in clinical efficacy and patientreported QoL. A large percentage of tapinaroftreated patients achieved a DLQI of 0 or 1, i.e., no negative effects of disease on QoL. Correlations between improvements in DLQI and clinical efficacy measures suggest that, beyond clinical improvements captured by the PASI and PGA, other important factors such as mental/emotional wellbeing and satisfaction with treatment contribute to the considerable overall improvement in QoL observed in these trials.

BACKGROUND:

Tapinarof cream 1% is an aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration to treat atopic dermatitis (AD) in patients down to age 2 years.

OBJECTIVE:

The aim of this study was to evaluate the safety and pharmacokinetics of tapinarof cream 1% once daily (QD) in adolescents and children with extensive AD under maximal usage conditions.

METHODS:

Patients with a validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥ 3 and body surface area (BSA) involvement ≥ 25% (ages 12-17 years) or ≥ 35% (ages 2-11 years) were enrolled into three age cohorts (2-6, 7-11, and 12-17 years) and received tapinarof cream 1% QD for 4 weeks.

RESULTS:

Overall, 36 patients (12 per cohort) were enrolled; mean BSA affected was 42.8% (range 26.0-90.0) and mean Eczema Area and Severity Index (EASI) score was 23.8. At baseline, 28 patients (77.8%) had a vIGA-AD™ score of 3 (moderate). No-to-minimal tapinarof systemic exposure was observed (25% of post-treatment plasma samples were below the quantifiable limit of a highly sensitive assay [< 50 pg/mL]). Mean maximum plasma concentration (Cmax) was 2.44 ng/mL, and median time to Cmax was 2.9 h. Eight patients (22.2%) reported treatment-emergent adverse events (TEAEs), which were mild or moderate; only one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Tapinarof was well tolerated, including on sensitive skin and extensor/flexural surfaces.

CONCLUSION:

Tapinarof cream exhibits highly favorable safety and pharmacokinetics in adolescents and children down to age 2 years with extensive AD.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT05186805.

Tapinarof is a first-in-class, nonsteroidal, topical, aryl hydrocarbon receptor agonist approved by the Food and Drug Administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of atopic dermatitis (AD) in adults and children. Tapinarof cream 1% once daily (QD) demonstrated significant efficacy vs. vehicle and was well tolerated in adults and adolescents with moderate to severe AD in a previously reported phase 2b trial. The pharmacokinetic (PK) profile of tapinarof across psoriasis and AD trials in adults is characterized by no-to-minimal systemic absorption and decreasing plasma concentrations over the course of treatment. Here, we report PK, tolerability and safety of tapinarof cream 1% QD in adolescents and children down to age 2 years with extensive AD. Adolescents and children with a Validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥3 (moderate or worse) and body surface area (BSA) involvement ≥25% (ages 12-17 years) or ≥35% (ages 2-11 years) were enrolled into three age cohorts (2-6, 7-11 and 12-17 years) and were treated with tapinarof cream 1% QD for 4 weeks. Primary endpoints included PK parameters, investigator-assessed Local Tolerability Scale (LTS) scores by visit (overall and for sensitive areas) and treatment-emergent adverse events (TEAEs). Overall, 36 patients (12 per cohort) were enrolled. Patients' mean age was 8.9 years and 66.7% were male. At baseline, 66.7%, 75% and 91.7% of patients had a vIGA-AD score of 3 for cohorts 2-6, 7-11 and 12-17 years, respectively. Mean BSA (range) affected was 52.4% (36.0- 90.0%), 42.0% (35.0-72.0%) and 33.9% (26.0-54.5%) for the three age cohorts, respectively. Mean Eczema Area and Severity Index scores were 30.2, 21.0 and 20.3, respectively. No-to-minimal tapinarof systemic exposure was observed, consistent with previous trials in adults. Mean tapinarof maximum plasma concentration (Cmax ) at Day 1 was 2.4 ng/mL, and the median time to Cmax was approximately 3 h, for all patients. Approximately 25% of post-treatment plasma samples were below the quantifiable limit of the highly sensitive assay [<50 pg (10 )/mL]. There was no correlation between tapinarof exposure (Cmax on Day 1) and baseline %BSA affected. Mean overall investigator-assessed LTS score was 0.1 (no irritation) at Weeks 1 and 4. Investigators assessed that the majority of patients had no irritation (LTS score of 0), including sensitive and intertriginous skin. The TEAEs were reported by eight patients (22%) and were all mild or moderate; one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Most patients (87.5%) chose to enroll in the 48-week long-term extension trial. This is the first trial evaluating tapinarof in children down to 2 years of age. Tapinarof cream 1% QD demonstrated no-to-minimal systemic exposure in children with extensive AD, even when measured with a highly sensitive assay. There was a low incidence of TEAEs in patients with up to 90% BSA affected. Tapinarof cream was well tolerated, including sensitive and intertriginous skin areas.