Tapinarof

Plaque psoriasis is a common, chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic well demarcated lesions that can be painful and disfiguring. The burden of psoriasis is reported to be like that of other chronic conditions, such as congestive cardiac failure and chronic lung disease, and includes significant physical, psychological, and socioeconomic burden. Tapinarof (Vtama – GSK) is a novel, first-in-class, small-molecule topical therapeutic aryl hydrocarbon receptor (AhR)-modulating agent (TAMA) recently approved by FDA (May 2022) for the treatment of psoriasis and atopic dermatitis. The compound was co-developed by Welichem Biotech and Stiefel Laboratories (subsidiary of GSK). However, Shenzhen Celestial Pharmaceuticals obtained rights to the product in the Greater China region (China, Taiwan, Macao and Hong Kong) in 2005. In 2012, Welichem licensed development and commercialization rights in all other regions to Stiefel. In 2013, Welichem entered into an asset purchase agreement to regain Greater China rights to the product from Tianji Pharma and Celestial; however, this agreement was terminated in 2014. In 2018, Stiefel transferred its product license to Dermavant Sciences. Tapinarof mechanism of action inhibits two pro-inflammatory pathways implicated in psoriasis (Th17 cytokines: IL-17A; IL-17F) and atopic dermatitis (Th2 cytokines: IL-4; IL-5; IL-13). It is believed that the AhR modulation by tapinarof also increases antioxidant activity via upregulation of Nrf2 and promotes skin barrier restoration through upregulation of a number of epidermal barrier genes, including filaggrin, hornerin, and involucrin. Tapiranof was first discovered as a metabolite (3,5-dihydroxy-4-isopropylstilbene) produced in Photorhabdus luminescens, a gram-negative bacillus that lives symbiotically with the Heterorhabditis nematodes. In 1959, it was noticed that Heterorhabditis with a high amount of 3,5-dihydroxy-4-isopropylstilbene did not putrefy once dead, thus suggesting its potential anti-inflammatory activity. The efficacy and tolerability of tapinarof in psoriasis clinical trials is attributed to its unique mechanism of action, representing an important potential advance in the development of topical medicine.