Treat-to-Target Outcomes and Measures of Treatment Success in Three Phase 3 Trials of Tapinarof Cream 1% Once Daily for Mild to Severe Plaque Psoriasis
April W. Armstrong,1 Robert Bissonnette,2 Philip M. Brown,3 Anna M. Tallman,3 Kim A. Papp4

1Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Innovaderm Research Inc., Montreal, QC, Canada; 3Dermavant Sciences, Inc., Morrisville, NC, USA; 4Probity Medical Research Inc., Waterloo, ON, Canada

 INTRODUCTION 
■ Treat-to-target strategies are used in several chronic diseases to improve outcomes1

■ Treatment goals for psoriasis have been recommended by the US National Psoriasis Foundation (e.g., achieving a percent body surface area [%BSA] 
affected of ≤1.0% at 3 months) and the European S3-Guidelines on the Systemic Treatment of Psoriasis (e.g., achieving a ≥75% decrease in Psoriasis Area 
and Severity Index [PASI75] within 3–4 months)1,2

■ Analyses of a large cohort of patients treated with systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators 
Register) have shown that achieving an absolute PASI total score of ≤2 corresponded to achievement of a 90% decrease in PASI score (PASI90)3

■ In clinical practice, many patients fail to meet treatment targets, and current topical treatments alone are generally insufficiently efficacious4,5 

  –  Even with use of approved systemic agents, alone or in combination, a global study found that 57% of patients with moderate to severe plaque 
psoriasis had not achieved clear/almost clear skin on current therapy6

■ In addition, most topical therapies approved by the Food and Drug Administration (FDA) for psoriasis are restricted to ≤12 weeks of continuous use  
(e.g., ≤8 weeks for corticosteroids or calcipotriene, and ≤12 weeks for retinoids)7

■ Tapinarof (VTAMA®; Dermavant Sciences, Inc., USA) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the FDA for the 
treatment of plaque psoriasis in adults, and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis in adults 
and children down to 2 years of age8

■ 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 two identical, 12-week, pivotal phase 3 trials, PSOARING 1 (NCT03956355) and PSOARING 2 (NCT03983980)9,10

  –  Physician Global Assessment (PGA) response (PGA=0 or 1 and a ≥2-grade improvement from baseline by Week 12) was achieved by 35.4% and 40.2% 
of the tapinarof-treated patients versus 6.0% and 6.3% of vehicle-treated patients, respectively (both P<0.0001)

  –  PASI75 was achieved by 36.1% and 47.6% of the tapinarof-treated patients versus 10.2% and 6.9% of vehicle-treated patients by Week 12, 
respectively (both P<0.0001)

■ In PSOARING 3 (NCT04053387), the long-term extension trial in which patients received intermittent or continuous tapinarof treatment, efficacy 
continued to improve beyond the 12-week trials, with a 40.9% rate of complete disease clearance (PGA=0), ~4-month remittive effect off therapy, and 
durability of response on therapy of up to 52 weeks11 

 OBJECTIVE
■ To present analyses of treat-to-target outcomes for patients treated with tapinarof cream 1% QD in the PSOARING trials, including more-aggressive 

targets of the proportion of patients achieving an absolute PASI total score of ≤1, ≤2, or ≤3, or a %BSA affected of ≤1% or ≤0.5%

 MATERIALS AND METHODS
Trial Design 
■ Pooled efficacy analyses included all patients who had a baseline PGA score of ≥2 (mild or worse) before tapinarof cream 1% QD treatment in the 

PSOARING trials (Figure 1) 
■ This included: 
  –  Patients assigned to vehicle in PSOARING 1 and 2 who received tapinarof in PSOARING 3
  –  Patients who received intermittent or continuous tapinarof treatment in PSOARING 3 based on their PGA score (where those who entered with, or 

achieved, a PGA score of 0 discontinued treatment and were observed for remittive effect [maintenance of PGA=0 or 1] while off therapy; if disease 
worsening occurred [PGA≥2], tapinarof cream was restarted and continued until a PGA=0 was achieved)

Figure 1. PSOARING 1, 2, and 3 Trial Design  

*Patients with PGA=2 (mild) and PGA= 4 (severe) limited to ~10% each of the total randomized population; ~80% of the total randomized population with PGA=3 (moderate). †Patients electing not to 
participate in the LTE trial had a follow-up visit 4 weeks after completion of the treatment period. 
BSA, body surface area; LTE, long-term extension; PGA, Physician Global Assessment; QD, once daily; R, randomized.

Endpoints and Statistical Analysis 
■ Proportion of patients who achieved a PASI total score of ≤3, ≤2, or ≤1
■ Proportion of patients who achieved a %BSA affected of ≤1.0% or ≤0.5%
■ Efficacy analyses were based on pooled data from observed cases; time-to-event analyses were based on Kaplan–Meier estimates
■ The safety population included all patients who received tapinarof in the PSOARING trials

 RESULTS 
Baseline Patient Demographics and Disease Characteristics 
■ Overall, 915 eligible patients were included in the pooled efficacy analyses (Table 1)
■ Mean age was 50.2 years, 58.7% were male, mean weight was 92.2 kg, and mean body mass index was 31.6 kg/m2

■ 78.1% had a PGA score of 3 (moderate), mean PASI score was 8.7, and mean BSA affected was 7.8%

Table 1. Baseline Disease Characteristics (Pooled Analysis)

Tapinarof cream 1% QD  
(n=915)

PGA, n (%)

2 – Mild 127 (13.9)

3 – Moderate 715 (78.1)

4 – Severe 73 (8.0)

PASI, mean (SD) 8.7 (4.2)

BSA affected, %, mean (SD) 7.8 (5.0)

BSA, body surface area; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; QD, once daily; SD, standard deviation.  

Achievement of Absolute PASI Total Score of ≤3, ≤2, or ≤1  
■ PASI scores of ≤3, ≤2, and ≤1 were achieved by 75.0% (n=686), 66.9% (n=612), and 50.3% (n=460) of patients, respectively (Figure 2) 
■ The median time to target (95% confidence interval [CI]) was 58 (57–63) days, 87 (85–110) days, and 185 (169–218) days for achieving PASI ≤3, ≤2, and 

≤1, respectively

Figure 2. Proportion of Patients Achieving Absolute PASI Treatment Targets (Total Score of ≤3, ≤2, or ≤1)* 

*Median time to PASI ≤3: 58 (95% CI, 57–63) days; median time to PASI ≤2: 87 (95% CI, 85–110) days; median time to PASI ≤1: 185 (95% CI, 169–218) days.  

The analysis population included patients receiving intermittent treatment with tapinarof, due to the forced-withdrawal design of PSOARING 3 (treatment withdrawal when patients achieved PGA= 0). 
Pooled analysis, OC.  
CI, confidence interval; OC, observed cases; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; QD, once daily.

Achievement of %BSA Affected of ≤1.0% or ≤0.5%  
■ The analyses indicated that 61.3% of patients (n=561) achieved %BSA of ≤1.0%, with a median time to target of 120 (95% CI, 113–141) days (Figure 3A)
  –  In addition, 40% (95% CI, 37%–43%) achieved the guideline-recommended target1 of %BSA of ≤1.0% at 3 months (90 days)
■ %BSA of ≤0.5% was achieved by 49.7% (n=455) of patients, with a median time to target of 199 (95% CI, 172–228) days (Figure 3B)

Figure 3. Proportion of Patients Achieving BSA Treatment Targets (≤1.0% or ≤0.5%)* 

*Median time to BSA ≤1.0%: 120 (95% CI, 113–141) days; median time to BSA ≤0.5%: 199 (95% CI, 172–228) days. 

The analysis population included patients receiving intermittent treatment with tapinarof, due to the forced-withdrawal design of PSOARING 3 (treatment withdrawal when patients achieved PGA= 0). 
Pooled analysis, OC.  
BSA, body surface area; CI, confidence interval; OC, observed cases; PGA, Physician Global Assessment; QD, once daily.

Absolute PASI ≤1 and %BSA of ≤0.5% Achieved by Week 4   
■ Figure 4 shows the clinical response for a patient with plaque psoriasis treated with tapinarof cream 1% QD, whose improvement by Week 4 exceeded 

the absolute PASI, %BSA, and PGA endpoints 

Figure 4. Total PASI, BSA, and PGA Scores at Baseline, Week 4, and Week 12 in a Patient with Moderate Plaque Psoriasis Treated with Tapinarof 
Cream 1% QD

PGA, PASI, and BSA are global efficacy assessments. Example of one representative target lesion of one tapinarof-treated patient from the PSOARING 2 clinical trial. Individual results may vary. 
BSA, body surface area; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; QD, once daily.

Safety   
■ Treatment-emergent adverse events (TEAEs) were mostly mild to moderate
■ The most common TEAEs (in ≥5% of patients) were folliculitis, contact dermatitis, and nasopharyngitis

 CONCLUSIONS
■ Tapinarof cream 1% QD was well tolerated and demonstrated rapid, clinically meaningful, and durable improvements in clinical efficacy in a high 

proportion of patients 
■ Treatment targets were achieved with tapinarof cream monotherapy, despite the challenges of meeting these goals with available systemic, biologic, 

topical, and combination therapies
■ The aggressive target of ≤1% BSA affected was achieved by 40% of tapinarof-treated patients within ~3 months; attainment continued to increase over 

time, with 50% of patients achieving this target at ~4 months
■ These findings support continuing tapinarof treatment beyond 3 months for patients who are experiencing improvement but not yet meeting the ≤1% 

BSA affected treatment target advocated by the National Psoriasis Foundation12

■ An absolute PASI total score of ≤2 was achieved by 67% of tapinarof-treated patients; this is a treatment target that has been shown to correspond to a 
PASI90 response3 

■ These analyses may have underestimated the percentage of patients who achieved treatment targets, due to the unique forced-withdrawal design of 
PSOARING 3 that resulted in intermittent rather than continuous treatment

 REFERENCES
1. Armstrong AW, et al. J Am Acad Dermatol. 2017;76:290–298. 2. Pathirana D, et al. J Eur Acad Dermatol Venereol. 2009;23:5–70. 3. Mahil SK, et al. Br J Dermatol. 
2020;182:1158–1166. 4. Strober BE, et al. Dermatol Ther.  2019;9:5–18. 5. Bagel J and Stein Gold L. J Drugs Dermatol. 2017;16:1209–1222. 6. Armstrong A, et al. J Eur 
Acad Dermatol Venereol. 2018;32:2200–2207. 7. Elmets CA, et al. J Am Acad Dermatol. 2021;84:432-470. 8. Dermavant Sciences. VTAMA (tapinarof) cream, 1%: US 
prescribing information. 2022. https://www.vtama.com/docs/DMVT_VTAMA_PI.pdf. Accessed 22 July 2022. 9. Lebwohl M, et al. N Engl J Med. 2021;385:2219–2229. 
10. Lebwohl M, et al. Presentation at: European Academy of Dermatology and Venereology; October 28 - November 1, 2020. 11. Strober B, et al. J Am Acad Dermatol. 
2022. https://doi.org/10.1016/j.jaad.2022.06.1171. 12. National Psoriasis Foundation. Treat to Target. https://www.psoriasis.org/treat-to-target/. Accessed August 2022.     

 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. A.W.A. is a research investigator and/or scientific advisor to AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant Sciences, Inc., Dermira, EPI, Incyte, 
Janssen, LEO Pharma, Eli Lilly, Modmed, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sun Pharma, Sanofi, and UCB Biopharma. R.B. has served as a consultant/
investigator/advisory board member for AbbVie, Alumis, Almirall, Amgen, AnaptysBio, Arcutis, Aristea, Bausch Health, Boehringer Ingelheim, Boston Pharmaceuticals, 
Bristol Myers Squibb, Dermavant Sciences, Inc., Eli Lilly, Escalier, Janssen, Kyowa Kirin, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, Sienna, and UCB Biopharma; 
and is an employee and shareholder of Innovaderm Research. P.M.B., and A.M.T. are employees of Dermavant Sciences, Inc., with stock options. K.A.P. is a consultant/
speaker/scientific officer/has attended advisory boards for, or received grants or honoraria from, AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, 
Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, 
Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck (MSD), Merck-Serono, Mitsubishi Pharma, Moberg Pharma, 
Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, and UCB Biopharma. 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 April W. Armstrong at april.armstrong@med.usc.edu/aprilarmstrong@post.harvard.edu with questions or comments.

Adult patients
with mild to severe

plaque psoriasis

• Aged 18–75
 years old

• PGA score ≥2*

• BSA ≥3% to ≤20%

Double-blind
treatment
(12 weeks)

2:1

2:1

Tapinarof 1% QD
(n=340)

Tapinarof 1% QD
(n=343)

Vehicle QD
(n=170)

Vehicle QD
(n=172)

(N=510)

(N=515)

R

R

Off treatment

Off
treatment

PGA=0
(n=79)

PGA=0
Stop

treatment

PGA≥2
Re-start

treatment

PGA≥1
(n=680) Tapinarof 1% QD

Long-term 
open-label extension

(40 weeks)†
Follow-up
(4 weeks)

A. PASI score of ≤3 B. PASI score of ≤2 C. PASI score of ≤1

0

10

20

30

40

50

60

70

80

Tapinarof 1% QD
(686/915)

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10

20

30

40

50

60

70

80

Tapinarof 1% QD
(612/915)

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10

20

30

40

50

60

70

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Tapinarof 1% QD
(460/915)

75%
67%

50%

A. BSA of ≤1.0%

0

10

20

30

40

50

60

70

80

Tapinarof 1% QD
(561/915)

61%

P
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B. BSA of ≤0.5%

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50

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Tapinarof 1% QD
(455/915)

50%

P
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• •

• PASI=14.7   • BSA=15.3%

• PGA=3

BASELINE WEEK 4 WEEK 12

• PASI=10.9   • BSA=0.3%

• PGA=1

• PASI=0   • BSA=0%

• PGA=0