The rise of TYK2 in the field of psoriasis in the JAK inhibitor war, who can break through, BMS, Pfizer, etc.

Text | April Chen

When JAK inhibitors are used in the development of areas that have already been captured by biological agents, people always pay attention to two issues.
One is whether the efficacy is comparable to that of biological agents? The second is whether the safety risks such as infection and thrombosis are controllable? These questions also existed when TYK2 specific inhibitors received the latest positive data on psoriasis
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The rise of JAK inhibitors in the field of autoimmune therapy

There are 4 protein tyrosine kinases in JAK family cells: JAK1, JAK2, JAK3 and TYK2
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Approved JAK inhibitors for autoimmune diseases

The first and second-generation JAK inhibitors that have been marketed mainly targeting JAK subtypes have obtained the largest indication population in autoimmune diseases-RA, and the current TYK2 specific inhibitors attack another autoimmune group.
Population-psoriasis, no JAK inhibitor has been approved yet
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Psoriasis curative effect standards are improving

Compared with biologics that target a single cytokine, JAK inhibitors show multiple advantages, can block multiple cytokines, and theoretically increase the range of diseases that a drug can treat.
It can be administered orally or as a topical drug.
Compared with the intravenous/subcutaneous administration of biological preparations, the administration of the drug improves the convenience of clinical use and patient compliance, and basically does not produce anti-drug antibodies that may be produced by biological preparations
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TYK2, once considered to have an unknown role, has been found to mediate the conduction of signals such as IL-6, IL-10, IL-12, IL-23 and type I interferon, which covers the current thought to be the key to the progression of psoriasis disease The positive clinical results of cytokines IL-12 and IL-23, and BMS and Pfizer, which were the first to bet on TYK2 specific inhibitors in the early years, on psoriasis also confirmed this
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The competitive landscape of psoriasis large-molecule and small-molecule targeted drugs

PASI 75 (psoriasis area and severity index score improved by 75% compared to baseline) is one of the main endpoints of clinical trials of new psoriasis drugs.
There is fierce competition in macromolecules.
Traditional anti-TNFα antibodies are effective for patients with psoriasis.
In the 12th week, the PASI 75 remission rate was only 50-70%, and the risk of inducing tuberculosis recurrence was higher, and then the interleukin inhibitors on the market increased the PASI remission rate to about 80%
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POETYK PSO-1 and 2 test effectiveness results

Security challenges and competition

Recently, the FDA's PDUFA application for Pfizer's Abrocitinib for the treatment of atopic dermatitis has been delayed by three months from the previously designated April 2021
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POETYK PSO-1 test safety results

At present, Deucravacitinib may become the first TYK2 inhibitor to be marketed for psoriasis, but it faces a lot of competition.
There are IL-17 and IL-23 antibodies that have been marketed before, and IL-17 is still under research Antibody Bimekizumab, and other TYK2 inhibitors
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Although the effectiveness and safety of a new generation of TYK2 specific inhibitors in psoriasis, UC, SLE and other indications are still being explored, the pharmaceutical industry is also increasingly interested in the development of this target