Deucravacitinib: First Approval

Abstract

Deucravacitinib (SOTYKTU™) is a first-in-class, highly selective, oral tyrosine kinase 2 (TYK2) inhibitor. It acts via an allosteric mechanism, binding to the catalytically inactive pseudokinase regulatory domain of TYK2 and stabilizing an inhibitory interaction between the regulatory and catalytic domains. Deucravacitinib is being developed by Bristol Myers Squibb for the treatment of multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. It received its first approval (in the USA on 9 September 2022) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. On 26 September 2022, it was subsequently approved in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis. The Marketing Authorisation Application for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis has been validated in the EU, and clinical development of the drug for the treatment of multiple immune-mediated diseases is underway in numerous countries worldwide. This article summarizes the milestones in the development of deucravacitinib leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01796-y.

Tyk2 Targeting in Immune-Mediated Inflammatory Diseases

“…Thus, Tyk2 is an attractive druggable target, and multiple Tyk2 inhibitors are being investigated [ 10 , 13 , 22 ]. Deucravacitinib has become the first Tyk2 inhibitor approved for moderate to severe psoriasis treatment [ 73 ], but potential indications in other IMIDs are multiple and the therapeutic potential of Tyk2 inhibitors are not limited to psoriatic disease.…”

“…Most Jak and Tyk inhibitors are orthosteric, binding at the active tyrosine kinase site and competing with ATP, as opposed to the allosteric inhibition of deucravacitinib and BMS-986202, which bind to the pseudokinase JH2 (regulatory) domain of Tyk2, providing unparalleled selectivity [ 10 , 65 , 73 ]. As demonstrated in clinical trials of deucravacitinib, this unique mechanism of action limits the side effects of deucravacitinib and, expectedly, BMS-986202 [ 10 , 22 , 71 , 72 ].…”

“…Subsequently, on 26 September 2022, it was approved in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis, and erythrodermic psoriasis. Currently, deucravacitinib is under consideration by the European Medicines Agency [ 73 ].…”

“…On 9 September 2022, deucravacitinib became the first oral Tyk2 inhibitor approved by the USA Food and Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis. Two weeks later, the Japanese regulatory agency approved deucravacitinib for the treatment of plaque psoriasis, generalized pustular psoriasis, and erythrodermic psoriasis [ 73 ]. Approval by the European Medicines Agency is still pending.…”

More New Therapeutics for Psoriasis

“…It was approved for adults with moderate to severe plaque psoriasis in September 2021. 7 We know patients want oral treatment; they ask for apremilast even though injections may be much more potent. In a 16-week, phase 3 clinical trial comparing daily deucravacitinib (n=332), apremilast (n=168), and placebo (n=166), rates of clear or almost clear were approximately 55% in the deucravacitinib group, 32% in the apremilast group, and 7% with placebo.…”