Oral TYK2 Inhibitor Zasocitinib Shows Promising Efficacy in Plaque Psoriasis
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on September 13th, 2024
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Psoriasis is an inflammatory condition primarily driven by interleukin 17 and T-helper 17 cells. While there are several effective treatments targeting these pathways, the options for oral administration are limited. Zasocitinib is an orally bioavailable agent that inhibits TYK2, a key component of the intracellular signaling pathway in immune cells, by interfering with JAK protein transduction. A study, sponsored by Nimbus Discovery and Takeda, was conducted to investigate the efficacy of zasocitinib in managing plaque psoriasis.
The phase 2 clinical trial involved 259 participants diagnosed with moderate to severe plaque psoriasis, characterized by a physician global assessment (PGA) score of 3 or 4 and affecting over 10% of body surface area. The cohort had an average Psoriasis Area and Severity Index (PASI) score of 22 out of 72 and a baseline Dermatology Life Quality Index (DLQI) score of 12, with 30 indicating the most debilitating level of the disease. Participants were randomly assigned to receive either placebo or one of four doses of zasocitinib (2, 5, 15, and 30 mg) orally once daily. After 12 weeks, zasocitinib demonstrated significant efficacy in resolving plaque psoriasis, with nearly 70% of participants in the 15 mg and 30 mg groups achieving a 75% reduction in PASI score, and one-third of those in the highest dose group achieving a PASI score of 0. Additionally, the PGA assessment indicated that zasocitinib effectively reduced disease severity to a score of 0 or 1. Unlike previous studies on deucravacitinib, which reported a high frequency of treatment-emergent adverse events, this study found a lower incidence with zasocitinib, which the authors attributed to its higher selectivity for the JH2 domain of TYK2, reducing off-target effects.
The phase 2 clinical trial involved 259 participants diagnosed with moderate to severe plaque psoriasis, characterized by a physician global assessment (PGA) score of 3 or 4 and affecting over 10% of body surface area. The cohort had an average Psoriasis Area and Severity Index (PASI) score of 22 out of 72 and a baseline Dermatology Life Quality Index (DLQI) score of 12, with 30 indicating the most debilitating level of the disease. Participants were randomly assigned to receive either placebo or one of four doses of zasocitinib (2, 5, 15, and 30 mg) orally once daily. After 12 weeks, zasocitinib demonstrated significant efficacy in resolving plaque psoriasis, with nearly 70% of participants in the 15 mg and 30 mg groups achieving a 75% reduction in PASI score, and one-third of those in the highest dose group achieving a PASI score of 0. Additionally, the PGA assessment indicated that zasocitinib effectively reduced disease severity to a score of 0 or 1. Unlike previous studies on deucravacitinib, which reported a high frequency of treatment-emergent adverse events, this study found a lower incidence with zasocitinib, which the authors attributed to its higher selectivity for the JH2 domain of TYK2, reducing off-target effects.