Exposure–Response Analysis Demonstrates Response to Tapinarof is Driven by Local Effects at Sites of Application 
James Del Rosso,1 Scott Guenthner,2 H. Chih-ho Hong,3 John E. Jett,4 Philip M. Brown,4 David S. Rubenstein,4 Stephen C. Piscitelli4

1JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, USA; 2The Indiana Clinical Trials Center, Plainfield, IN, USA; 3University of British Columbia and Probity Medical Research, Surrey, BC, Canada; 4Dermavant Sciences Inc., Morrisville, NC, USA 

 INTRODUCTION 
■ Tapinarof (VTAMA®; Dermavant Sciences, Inc., USA) is a first-in-class, non-steroidal, 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 plaque psoriasis in children down to 2 years of age and for atopic dermatitis (AD) in adults and children 
down to 2 years of age1

■ Tapinarof cream 1% once daily (QD) demonstrated significant efficacy versus vehicle and was well tolerated in adults 
with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, PSOARING 1 (NCT03956355) and 
PSOARING 2 (NCT03983980)2

■ In the long-term extension trial, PSOARING 3 (NCT04053387), tapinarof was well tolerated and demonstrated a high rate of 
complete disease clearance, ~4-month remittive effect off therapy, and durability on therapy for up to 52 weeks3

■ Topical agents that are locally effective with minimal systemic exposure are desirable for dermatologic conditions

■ There is a need for efficacious, non-steroidal topical therapies for patients with psoriasis, without restrictions relating to 
duration, extent of use, and application sites

■ In a phase 2a trial, topical application of tapinarof cream 1% QD under maximal use conditions in patients with extensive 
psoriasis (up to 46% body surface area [BSA] involvement) resulted in minimal systemic exposure4

 OBJECTIVE
■ To evaluate the hypothesis that there is no relationship between tapinarof plasma exposure and either safety or efficacy

 METHODS
Trial Design
■ Analyses included data from 4 clinical trials of tapinarof in patients with AD or plaque psoriasis across a range of doses, 

patient populations, and BSA involvement (Table 1)

Table 1. Clinical Trials Included in Tapinarof Exposure–Response Analyses

Patients with AD Patients with Plaque Psoriasis

Phase 2b  
Dose-finding Trial 

(N=247)5

Phase 2a  
Maximal-use Trial 

(N=21)4

Pivotal Phase 3 Trials2

PSOARING 1 (N=510) PSOARING 2 (N=515)

Trial design
Randomized, double-

blind, vehicle-controlled
Open-label Randomized, double-blind, vehicle-controlled

Eligibility criteria

Patient population AD with IGA score ≥3
Plaque psoriasis with 

PGA score ≥3
Plaque psoriasis with PGA score ≥2

Age 12–65 years 18–75 years 18–75 years

BSA involvement 5%–35% ≥20% 3%–20%

Trial drug

Tapinarof cream: 
 0.5% QD, 0.5% BID,

1% QD, 1% BID
Vehicle cream:

QD or BID

Tapinarof cream: 
1% QD

Tapinarof cream:  
1% QD 

Vehicle cream: 
QD 

PK sampling Weeks 1, 2, 4, 8, and 12 Days 1, 15, and 29 Weeks 4 and 12

AD, atopic dermatitis; BID, twice daily; BSA, body surface area; IGA, Investigator Global Assessment; PGA, Physician Global Assessment; PK, pharmacokinetic; QD, once daily. 

Pharmacokinetic Sampling and Exposure Parameters 

■ Tapinarof plasma concentrations were measured using a highly sensitive assay that permitted assessment of drug levels to 
picogram (pg [10-12 g])/mL level

  –  The lower limit of quantitation (LLOQ) was 50 pg/mL in the psoriasis trials and 40 pg/mL in the AD trial

■ Because most samples were below the LLOQ (BLQ), the exposure–response analysis used imputed concentration values for 
BLQ samples that assumed an exposure level of approximately half of the LLOQ

■ PK parameters were the minimum and maximum plasma concentrations (C
min

 and C
max

) of tapinarof

Endpoints and Statistical Analysis  

■ Tapinarof plasma concentrations were evaluated for relationships with disease (AD or plaque psoriasis), tapinarof dose (0.5% 
or 1%), and application frequency (QD or twice daily [BID])

■ A separate analysis of the maximal-use trial in psoriasis investigated whether tapinarof exposure correlated with percentage 
BSA affected at baseline

■ To investigate any relationship between tapinarof exposure and safety endpoints, tapinarof exposure (C
min

 and C
max

) was 
categorized as follows: 

  –  ‘0’ (patients randomized to vehicle) 
  –  ‘≤BLQ’ (patients with undetectable tapinarof exposure) 
  –  ‘>BLQ’ (patients with measurable tapinarof concentrations)
  –  The >BLQ group was then grouped into tertiles of exposure
■ Safety assessments included adverse events of special interest (AESIs): folliculitis, contact dermatitis, and headache
■ Efficacy assessments in patients with psoriasis included Physician Global Assessment (PGA) scores on Day 29 and change 

from baseline in Psoriasis Area and Severity Index (PASI) scores on Day 29
■ The relationship between tapinarof exposure and efficacy was not assessed in patients with AD
■ Demographics and PK concentrations were assessed in patients who received ≥1 dose of trial drug and had ≥1 PK sample 

(PK population)
■ Efficacy–response analyses were assessed in all patients who received ≥1 dose of trial drug (safety population)

 RESULTS 
Patient Baseline Characteristics   
■ The majority of patients (58.9% [346/587]) had plaque psoriasis; 53.8% overall were male; and the mean age was 

41.8 years (Table 2)
■ Overall, 67.8% (398/587) of patients received tapinarof and 32.2% (189/587) received vehicle
  –  Among patients in the tapinarof groups, most (69.8%) received tapinarof 1% QD; the remainder received tapinarof 0.5% 

QD (9.8%), 0.5% BID (10.3%), or 1% BID (10.1%)

Table 2. Baseline Patient Demographics (PK Population)

Patients with AD Patients with Plaque Psoriasis

Overall 
(N=587)Phase 2b Trial 

(N=241)5
Phase 2a  

Maximal-use Trial 
(N=21)4

Pivotal Phase 3 Trials2

PSOARING 1 
(N=139)

PSOARING 2 
(N=186)

Age, years, mean (SD) 29.5 (14.9) 51.8 (13.9) 47.9 (13.4) 52.1 (12.4) 41.8 (17.2)

Male, n (%) 122 (50.6) 13 (61.9) 70 (50.4) 111 (59.7) 316 (53.8)

Weight, kg, mean (SD) 76.8 (24.0) 97.5 (24.6) 94.1 (25.2) 93.0 (23.1) 86.8 (25.4)

BMI, kg/m2, mean (SD) 27.5 (7.6) 33.1 (7.9) 32.2 (8.5) 31.8 (7.4) 30.1 (8.1)

AD, atopic dermatitis; BMI, body mass index; PK, pharmacokinetic; SD, standard deviation.     

Pharmacokinetics of Tapinarof  
■ Tapinarof plasma exposure was low overall and below quantifiable limits in the majority (62.6% [1243/1985]) of samples using a 

highly sensitive assay 
■ Mean (SD) C

min
 and C

max
 were 27.6 (23.3) pg/mL and 340 (6270) pg/mL, respectively

■ There were no trends observed between tapinarof plasma concentrations and disease (AD or psoriasis), or the concentration of 
tapinarof cream (0.5%, 1%), or frequency (QD, BID) of application (Figure 1)

■ In a separate, post hoc analysis of the psoriasis maximal-use trial, there was also no correlation between tapinarof plasma 
concentration and BSA in patients with psoriasis (ranging from 21%–46%) (Figure 2)

■ In the maximal-use trial in patients with psoriasis, tapinarof plasma exposure declined over time, and was approximately 10-fold lower 
on Day 29 than on Day 14

Figure 1. Tapinarof Plasma Concentrations Over Time Remained Low in AD and Psoriasis Trials, Regardless of Dose or 
Application Frequency

*Horizontal lines indicate the LLOQ for the assays used in the psoriasis trials (50 pg/mL) and the AD trial (40 pg/mL). Dashed lines indicate median trend lines.  
AD, atopic dermatitis; BID, twice daily; LLOQ, lower limit of quantitation; QD, once daily. 

Figure 2. No Correlation Between Tapinarof Exposure (C
max

 on Days 1 and 29) and Baseline %BSA Affected in the Psoriasis 
Maximal-Use Trial

BSA, body surface area; C
max

 maximum plasma concentration.

Exposure–Response Analyses   
■ In the phase 2a maximal-use trial, there was no relationship between tapinarof plasma exposure and efficacy in patients with 

psoriasis, including improvements in PGA score and change from baseline in PASI score
■ There was no relationship between tapinarof exposure and AESIs of folliculitis, contact dermatitis, or headache in patients with AD or 

psoriasis across all trials
■ There was no correlation between tapinarof plasma exposure and PASI response on Day 29 (Figure 3) 

Figure 3. No Correlation Between Tapinarof Exposure (C
max

 on Day 29) and Change in PASI Score in Psoriasis Maximal-Use Trial

C
max

 maximum plasma concentration; PASI, Psoriasis Area and Severity Index.

 CONCLUSIONS
■ Tapinarof cream 1% QD is efficacious and well tolerated, including on intertriginous and sensitive skin areas, in patients with 

mild to severe plaque psoriasis
■ Topical application of tapinarof cream 1% QD in patients with psoriasis or AD resulted in minimal systemic exposure
■ The maximal-use trial in psoriasis demonstrated that tapinarof plasma exposure declined over time
■ Furthermore, tapinarof systemic exposure was also unrelated to %BSA affected for patients with psoriasis
■ This exposure–response analysis demonstrates a lack of dependence on systemic activity for the therapeutic efficacy of 

tapinarof cream

 REFERENCES
1. Dermavant Sciences. VTAMA (tapinarof) cream, 1%: US prescribing information. 2022. https://www.vtama.com/docs/DMVT_VTAMA_PI.pdf. Accessed July 2022.   
2. Lebwohl MG, et al. N Engl J Med. 2021;385:2219–2229. 3. Strober B, et al. J Am Acad Dermatol. 2022. https://doi.org/10.1016/j.jaad.2022.06.1171. 4. Jett JE, et al.   
Am J Clin Dermatol. 2022;23(1):83–91. 5. Peppers J, et al. J Am Acad Dermatol. 2019;80(1):89–98.

 ACKNOWLEDGMENTS
This trial was funded by Dermavant Sciences, Inc. The authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of 
the trial. J.D.R. serves as a consultant/advisor and clinical research investigator for Dermavant Sciences, Inc. S.G. is a speaker for AbbVie, Aclaris, Janssen, Pfizer, and Sun 
Pharma. H.C.H. has received consultancy fees, honorarium, and speaker fees from Dermavant Sciences, Inc. J.E.J., P.M.B., D.S.R., and S.C.P. are employees of Dermavant 
Science, Inc. with stock options. Editorial and medical writing support under the guidance of the authors was provided by ApotheCom, UK, and was funded by Dermavant 
Sciences, Inc. in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461–464). 

Contact Dr Del Rosso at jqdelrosso@yahoo.com with questions or comments.

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Tapinarof dose 
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frequency

Patient Population 
and Trials

N

–– 1% QD Psoriasis Phase 2a maximal-use trial
PSOARING 1 trial
PSOARING 2 trial 278

AD Phase 2b trial

–– 1% BID AD Phase 2b trial 40

–– 0.5% QD AD Phase 2b trial 39

–– 0.5% BID AD Phase 2b trial 41