Zasocitinib (TAK-279), a Highly Selective Oral TYK2 Inhibitor, Demonstrates Skin Clearance in Patients with Moderate-to-Severe Plaque Psoriasis: Post Hoc Analyses of a Randomized Phase IIb Trial

INTRODUCTION: Zasocitinib (TAK-279) is an investigational, once daily, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor. Post hoc analyses of a 12-week phase IIb trial in patients with moderate-to-severe plaque psoriasis evaluated zasocitinib 15 mg or 30 mg efficacy versus placebo by baseline characteristic subgroups, Psoriasis Area and Severity Index (PASI) improvements by body region and component scores, and patient-reported and other clinical outcomes. METHODS: Disease severity assessments included PASI, Physician's Global Assessment (PGA), body surface area (BSA), Dermatology Life Quality Index (DLQI) 0/1, and PGA × BSA. Subgroups included weight, sex, age, race, disease duration, prior biologic use, and PASI score. Body regions included head, trunk, and upper and lower extremities. Scoring components included erythema, induration, and desquamation. DLQI 0/1 attainment was assessed by PASI. RESULTS: At week 12, zasocitinib 15 mg or 30 mg demonstrated greater response rates in PASI 75/90/100 and PGA 0/1 in nearly all patient subgroups versus placebo. A greater proportion of patients receiving zasocitinib achieved PASI 75/90/100 across all PASI body regions and scoring components versus placebo. Reductions in BSA or PASI were greater in zasocitinib groups as early as week 2 and through week 12 versus placebo; most patients attaining PASI ≤ 1 or ≤ 2 or PASI 75/90/100 also achieved DLQI 0/1. Absolute PASI and PGA × BSA improvements were strongly positively correlated (ρ = 0.95), with PGA × BSA 75 and PASI 75 showing high agreement. CONCLUSION: Zasocitinib demonstrated consistent improvements in skin clearance, irrespective of baseline disease characteristics, PASI body region, and scoring component, with meaningful quality of life improvements. Graphical abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04999839.