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

John E Jett, Michael McLaughlin, Mark S Lee, Lawrence Charles Parish, Janet DuBois, Tooraj Joseph Raoof, Glenn Tabolt, Timothy Wilson, Matthew C Somerville, Wayne DellaMaestra, Stephen C Piscitelli, John E Jett, Michael McLaughlin, Mark S Lee, Lawrence Charles Parish, Janet DuBois, Tooraj Joseph Raoof, Glenn Tabolt, Timothy Wilson, Matthew C Somerville, Wayne DellaMaestra, Stephen C Piscitelli

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.

Conflict of interest statement

JEJ, WDM, MM, SCP, MCS, GT, and TW are employees of Dermavant Science, Inc. LCP is an investigator for Dermavant Science, Inc. JDB is an investigator for Allergan, Aclaris Therapeutics, Galderma USA, Brickell Biotech, Derma Therapeutics, Endo International, LEO Pharmaceuticals, Cara Therapeutics, Arcutis, Boston Pharmaceuticals, Atacama Therapeutics, Biofrontera, Bristol-Myers Squibb, RAPT Therapeutics, NFlection Therapeutics, Incyte Corporation, and Bellus Health. MSL is an investigator for Abbvie, Asana, Pfizer, Eli Lilly, AstraZeneca, Leo, Arena, Dermira, Cara, Bellus, Foamix, Arcutis, Incyte, UCB, and Boehringer Ingelheim. TJR has no conflicts of interest to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Patient disposition
Fig. 2
Fig. 2
Mean (+/− standard deviation) tapinarof plasma concentration vs time curves on a day 1 (baseline) and b day 29. All tapinarof sulfate concentrations were below the LLOQ of 10 pg/mL. Tapinarof LLOQ was 50 pg/mL. LLOQ lower limit of quantitation

References

    1. Parisi R, Symmons DPM, Griffiths CEM, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Investig Dermatol. 2012;133:377–385. doi: 10.1038/jid.2012.339.
    1. Boehncke WH, Schon MP. Psoriasis. Lancet. 2015;386:983–994. doi: 10.1016/S0140-6736(14)61909-7.
    1. Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient membership survey. Arch Dermatol. 2001;137:280–284.
    1. Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, et al; American Academy of Dermatology Association; Society for Investigative Dermatology. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55:490–500.
    1. Smith SH, Jayawickreme C, Rickard DJ, Nicoeme E, Gui T, Simmons C, et al. Tapinarof is a natural AhR agonist that resolved skin inflammation in mice and humans. J Investig Dermatol. 2017;137:2110–2119. doi: 10.1016/j.jid.2017.05.004.
    1. Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl hydrocarbon receptor in atopic dermatitis and psoriasis. Int J Mol Sci. 2019;20:5424. doi: 10.3390/ijms20215424.
    1. Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A. Tapinarof in the treatment of psoriasis: a review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA) J Am Acad Dermatol. 2021;84:1059–1067. doi: 10.1016/j.jaad.2020.10.085.
    1. Robbins K, Bissonette R, Maeda-Chubachi T, Ye L, Peppers J, Gallagher K, et al. Phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of plaque psoriasis. J Am Acad Dermatol. 2019;80:714–721. doi: 10.1016/j.jaad.2018.10.037.
    1. Peppers J, Paller AS, Maeda-Chubachi T, Wu S, Robbins K, Gallagher J, et al. A phase 2 randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019;80:89–98. doi: 10.1016/j.jaad.2018.06.047.
    1. Lebwohl M, Stein Gold L, Strober B, Armstrong A, Hong HC-H, Kircik L, et al. Tapinarof cream 1% QD for the treatment of plaque psoriasis: efficacy and safety in two pivotal phase 3 trials. SKIN J Cutan Med. 2020;4(6):s75.
    1. Bashaw ED, Tran DC, Shukla CG, Liu X. Maximal usage trial: an overview of the design of systemic bioavailability trial for topical dermatological products. Ther Innov Regul Sci. 2015;49:108–115. doi: 10.1177/2168479014539157.
    1. Garnett C, Bonate PL, Dang Q, Ferber G, Huang D, Liu J, et al. Scientific white paper on concentration-QTc modeling. J Pharmacokinet Pharmacodyn. 2018;45:383–397. doi: 10.1007/s10928-017-9558-5.
    1. Strober B. Tapinarof cream 1% once daily for plaque psoriasis: interim analysis of a long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent. Poster presentation presented at: Innovations in Dermatology Virtual Spring Conference; March 16–20, 2021.
    1. US Food and Drug Administration (FDA). In vitro drug interaction studies—cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry. US FDA Center for Drug Evaluation and Research (CDER). January 2020 Clinical Pharmacology. . Accessed 21 April 2021.

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