China's First TYK2 Inhibitor Deucravacitinib Approved for Market Launch

On October 19, the website of the National Medical Products Administration (NMPA) showed that Bristol-Myers Squibb's (BMS) TYK2 inhibitor deucravacitinib was approved for marketing in China, for the treatment of moderate to severe plaque psoriasis. This product is also the first TYK2 inhibitor approved for marketing in China.

Psoriasis is a widespread, chronic, systemic immune-mediated disease that seriously affects patients' physical health, life, and work. It troubles at least 100 million people worldwide. Plaque psoriasis is characterized by distinct round or oval plaques on the skin surface, covered with silvery-white scales. Existing systemic treatments have shown some therapeutic effects but fail to meet patients' needs. Many moderate-to-severe psoriasis patients remain either undertreated or untreated.

Deucravacitinib is an orally administered, highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) with a unique mechanism of action. It can selectively target TYK2 to inhibit the signaling of key cytokines (such as IL-23, IL-12, and type I interferons) involved in the pathogenesis of various immune-mediated diseases. Deucravacitinib achieves high selectivity by binding to the regulatory domain of TYK2, leading to the allosteric inhibition of TYK2 and its downstream functions. Within physiological concentration ranges, deucravacitinib selectively inhibits TYK2 without suppressing JAK1, JAK2, or JAK3 at therapeutic doses.

Mechanism of Action of Deucravacitinib (Source: AAD VMX 2021 BMS)

This approval is mainly based on the positive results of two pivotal Phase III clinical trials (POETYK PSO-1 and POETYK PSO-3). POETYK PSO-1 enrolled 666 patients, aiming to evaluate the efficacy and safety of deucravacitinib compared with apremilast and placebo in adult patients with moderate to severe plaque psoriasis. POETYK PSO-3 enrolled 220 patients, aiming to assess the efficacy and safety of deucravacitinib compared with placebo in adult patients with moderate to severe plaque psoriasis. The co-primary endpoints were the proportion of patients achieving PASI 75 (Psoriasis Area and Severity Index score improved by 75% or more) and sPGA 0/1 (static Physician's Global Assessment of skin symptoms as clear or almost clear) at week 16.

Results from the POETYK PSO-1 study showed that by week 16, the proportion of patients achieving PASI 75 and sPGA 0/1 was significantly higher in the deucravacitinib group compared to the placebo and apremilast groups. The trial also met all secondary endpoints, with deucravacitinib demonstrating significant and clinically meaningful improvements in symptom burden and quality of life measurements.

POETYK PSO-1 Study Results (Source: AAD VMX 2021 BMS)

POETYK PSO-3 Study Results Showed That at Week 16, 68.8% of Patients in the Deucravacitinib Group Achieved PASI 75, Superior to the Placebo Group (8.1%, P<0.0001); 38.2% of Patients Achieved PASI 90 (Psoriasis Area and Severity Index Improved by at Least 90%, i.e., Near Complete Clearance of Skin Lesions), Superior to the Placebo Group (1.4%, P<0.0001); Continued Treatment with Deucravacitinib Until Week 52 Maintained a Stable PASI 75 Response Rate, While the PASI 90 Response Rate Further Increased to 45.5%.

Notably, deucravacitinib has also demonstrated significant benefits in clearing lesions from difficult-to-treat areas (scalp). After 16 weeks of continuous treatment with deucravacitinib, 62.9% of patients with moderate to severe scalp psoriasis achieved ss-PGA 0/1 (scalp lesions cleared or almost cleared), surpassing the placebo group (9.8%, P<0.0001).

In addition to psoriasis, deucravacitinib is also being developed for the treatment of various immune diseases such as psoriatic arthritis, scalp psoriasis, systemic lupus erythematosus, and inflammatory bowel disease. Moreover, targeting the TYK2 pathway, Bristol-Myers Squibb has another drug, BMS-986322, currently in Phase II trials. It can be said that Bristol-Myers Squibb is a seasoned player in the TYK2 inhibitor field.

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