Over Half of Psoriasis Patients Achieve Near-Complete Skin Clearance: First-in-Class TYK2 Inhibitor Nears Approval

Today, Bristol-Myers Squibb (BMS) announced that the U.S. FDA has accepted the New Drug Application (NDA) for deucravacitinib, a potential "first-in-class" oral selective TYK2 inhibitor, and the European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis. The press release noted that deucravacitinib is expected to become the first approved TYK2 inhibitor.

Psoriasis, also known as psoriasis vulgaris, is a widespread chronic systemic immune-mediated disease that affects at least 100 million people worldwide. The disease is characterized by distinct round or oval plaques, typically covered with silvery-white scales. Psoriasis can cause significant psychological distress, and the associated pain can lead to functional disability, reduced work efficiency, and diminished quality of life. It is also associated with multiple comorbidities known to reduce life expectancy, including cardiovascular disease, metabolic syndrome, obesity, diabetes, inflammatory bowel disease, depression, and cancer.

TYK2 is a member of the JAK family and an intracellular signaling kinase that mediates signal transduction for IL-23, IL-12, and type I interferons (IFN). Multiple inhibitors targeting members of the JAK family have been approved for treating various diseases related to inflammation and immune responses. However, since members of the JAK family mediate signaling pathways of multiple cytokines, a key concern in the field has been how to reduce potential side effects. Deucravacitinib binds to the regulatory domain of TYK2, locking TYK2 in an inactive state, thereby selectively inhibiting TYK2 activity. This unique design allows it to avoid inhibiting other proteins in the JAK family, namely JAK1-3.

▲Deucravacitinib has a unique mechanism of action (Image source: Bristol-Myers Squibb's official website)

This regulatory submission is based on positive results from two pivotal Phase 3 clinical trials. These trials evaluated the efficacy of once-daily deucravacitinib in more than 1,600 patients with moderate to severe plaque psoriasis, compared with placebo and active control. The trial results demonstrated that, compared with placebo and active control, deucravacitinib showed significant and clinically meaningful improvements in skin clearance as assessed by PASI 75 and sPGA 0/1, as well as in symptom burden and quality of life measures. Additionally, deucravacitinib was well-tolerated with a low rate of discontinuation due to adverse events.

References:

[1] Bristol Myers Squibb’s Applications for Deucravacitinib for the Treatment of Moderate to Severe Plaque Psoriasis Accepted by U.S. Food and Drug Administration and Validated by European Medicines Agency. Retrieved November 29, 2021, from https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibbs-Applications-for-Deucravacitinib-for-the-Treatment-of-Moderate-to-Severe-Plaque-Psoriasis-Accepted-by-U.S.-Food-and-Drug-Administration-and-Validated-by-European-Medicines-Agency/default.aspx

(Original text has been abridged)

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