OBJECTIVE:

This article reviews the efficacy and safety of 1% tapinarof cream for plaque psoriasis.

DATA SOURCES:

A literature search was conducted from August 2022 to February 2023. The terms tapinarof, VTAMA, benvitimod, GSK2894512, DMVT-505, and WBI-1001 were queried in PubMed. ClinicalTrials.gov was searched to identify ongoing or unpublished studies.

STUDY SELECTION AND DATA EXTRACTION:

All clinical trials written in English and relevant to pharmacology, efficacy, and safety were included.

DATA SYNTHESIS:

In two 12-week phase III clinical trials, disease severity assessed by a Physician's Global Assessment (PGA) score of clear or almost clear and a 2-point PGA improvement was 35.4% and 40.2% at week 12 in the 2 trials, respectively. In the 40-week, open-label extension trial, the efficacy and safety results were similar: 40.9% of patients achieved a PGA of 0 at least once during the trial, and 58.2% of patients with PGA ≥ 2 achieved PGA 0/1 at least once.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS:

Tapinarof is a topical aryl hydrocarbon receptor agonist and a first-in-class, potentially promising treatment for plaque psoriasis recently approved by the U.S. Food and Drug Administration.

CONCLUSION:

Compared with placebo, tapinarof may be an effective and safe topical treatment for mild to severe plaque psoriasis. Head-to-head trials to compare the efficacy and adverse effect profile of tapinarof to other topical treatments are still needed, as are investigation in patients with recent or current use of phototherapy or biologic or nonbiologic systemics. Cost and adherence to treatment may be barriers for treatment efficacy.

Although topical drugs are the mainstay of treatment for patients with mild-to-moderate psoriasis, the developments observed in this field in the last two decades have been limited. The most commonly used drugs are still vitamin D analogues and corticosteroids, both with several limitations. The aryl hydrocarbon receptor (AhR) plays a role in the pathogenesis of psoriasis, and tapinarof, a novel, first-in-class, small molecule topical therapeutic AhR-modulating agent has been recently approved by the FDA for the topical treatment of plaque psoriasis in adults. Two large, 12-week, phase III trials, PSOARING 1 and 2, showed that 35.4%-40.2% of patients in the tapinarof 1% cream arm achieved the primary endpoint (Physician's Global Assessment [PGA] score of 0 or 1 and a decrease of ≥2-5 points at week 12) compared with 6.0%-6.3% for vehicle arm, respectively. The most common adverse effects were folliculitis, contact dermatitis, headache and pruritus. In the open label, 40-week, extension trial, PSOARING 3, the efficacy and safety results were similar, with 40.9% of patients achieving a PGA = 0 at least one time during the trial and 58.2% of patients with PGA≥2 achieved PGA = 0/1 at least once during the trial, without tachyphylaxis. There were no new safety signals, with most frequent adverse events being folliculitis, contact dermatitis, and upper respiratory tract infection. Tapinarof 1% cream has shown to be effective and to have a favorable safety profile in the treatment of psoriatic patients, representing an alternative to the current therapeutic options, increasing our armamentarium in the topical treatment of psoriasis.

To compare the safety and efficacy of the test (Tapinarof Cream 1%), placebo (vehicle cream) and reference VTAMA® (Tapinarof Cream 1%) treatments to demonstrate clinical equivalence in patients with plaque psoriasis.

Psoriasis is a chronic, immune-mediated, multisystem, inflammatory dermatological condition that is persistent and relapsing. Topical treatments are first line agents for mild to moderate plaque psoriasis. With proven efficacy and safety, topical corticosteroids are often used, although adverse effects and limitations for use exist. Tapinarof (Vtama®), a novel topical aryl hydrocarbon receptor modulating drug, was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults in May 2022. A literature search of PubMed, MEDLINE, and ClinicalTrials.gov was conducted using the following keywords: tapinarof, psoriasis, GSK2894512. Articles published before January 2023 were included in this review. This review describes the preclinical and clinical studies demonstrating the efficacy and safety of tapinarof, its place in therapy, and relevance to patient care. Kalabalik-Hoganson J, Nogid A, Frey K. A review of tapinarof: novel topical treatment for plaque psoriasis in adults. J Drugs Dermatol. 2023;22(8):761-765. doi:10.36849/JDD.7481.

VTAMA® (Tapinarof) 1% cream is a newly approved topical agent for treating plaque psoriasis. The active ingredient, tapinarof, binds to and activates aryl hydrocarbon receptors that positively regulate immune response and skin homeostasis. Tapinarof has presented promising results in two identical phase 3 randomized, double-blind, vehicle-controlled trials, where the primary efficacy end points were observed in 35.4% and 40.2% of patients in the tapinarof group compared to 6.0% and 6.3% of patients in the vehicle group. Tapinarof was applied once daily to affected psoriasis lesions for 12 weeks. Adverse events associated with tapinarof application were folliculitis, contact dermatitis, and headache. (SKINmed. 2022;20:298-300).

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that has wide-ranging roles, including regulation of inflammation and homeostasis. AhR is not a cell surface receptor; rather, it exists in a cytoplasmic complex that responds to a wide variety of structurally dissimilar endogenous, microbial, and environmental ligands. The ubiquitous expression of AhR, its ability to be activated by a wide range of ligands, and its capacity to act as a master regulator for gene expression and homeostasis make it a promising new therapeutic target. Clinical trials of tapinarof cream have now validated AhR agonism as a therapeutic approach that can deliver significant efficacy for treating inflammatory skin diseases, including psoriasis and atopic dermatitis. Tapinarof 1% cream is a first-in-class, nonsteroidal, topical, AhR agonist with a pharmacokinetic profile that results in localized exposure at sites of disease, avoiding systemic safety concerns, drug interactions, or off-target effects. Psoriasis and atopic dermatitis both involve epidermal inflammation, cellular immune responses, dysregulation of skin barrier protein expression, and oxidative stress. On the basis of the clinical effectiveness of tapinarof cream for treating inflammatory skin diseases, we review how targeting AhR may offer a significant opportunity in other conditions that share key aspects of pathogenesis, including asthma, inflammatory bowel disease, eosinophilic esophagitis, ophthalmic, and nervous system diseases.

This is a double-blind, randomized, vehicle controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% compared to vehicle control cream in pediatric and adult subjects with atopic dermatitis.

This study is a 12‐week double‐blind, vehicle‐controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 12 weeks. At the end of the 12‐week study treatment, qualified subjects completing the study will have the option to enter a separate open‐label, long‐term safety and efficacy study for an additional 40 weeks of treatment with tapinarof cream, 1%. Subjects who do not enroll in the open‐label long‐term study will complete a follow‐up visit approximately 4 weeks after end of treatment in this study (at Week 16).

This study is a 12‐week double‐blind, vehicle‐controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 12 weeks. At the end of the 12‐week study treatment, qualified subjects completing the study will have the option to enter a separate open‐label, long‐term safety and efficacy study for an additional 40 weeks of treatment with tapinarof cream, 1%. Subjects who do not enroll in the open‐label long‐term study will complete a follow‐up visit approximately 4 weeks after end of treatment in this study (at Week 16).

This is an open-label, multi-center, Phase 3 study to evaluate tapinarof cream, 1% in pediatric subjects with plaque psoriasis.