LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Linda F. Stein Gold
Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.
“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.
Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.
The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.
“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.
The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).
“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.
A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.
Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.
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