Safety and efficacy of envudeucitinib, a highly selective, oral allosteric TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis: Results from the 52-week open-label extension period of the phase 2 STRIDE study

BACKGROUND: Envudeucitinib (ESK-001), a highly selective, oral tyrosine kinase 2 inhibitor, was well-tolerated and effective in patients with plaque psoriasis in the STRIDE study. OBJECTIVE: To assess long-term safety and efficacy of envudeucitinib throughout 52 weeks in the ongoing phase 2 open-label extension in patients who completed STRIDE. METHODS: Patients completing STRIDE were eligible to enroll in the long-term open-label extension study (NCT05739435) and received envudeucitinib 40-mg once or twice daily. RESULTS: In the open-label extension which enrolled 165 patients, envudeucitinib was generally well-tolerated, with an overall 3.7% study drug discontinuation rate due to adverse events, as well as no clinically concerning laboratory or electrocardiogram findings. After 52 weeks of treatment with envudeucitinib 40-mg twice daily, 78% of patients achieved Psoriasis Area and Severity Index (PASI)-75, 61% achieved PASI-90, 39% achieved PASI-100, and 39% achieved sPGA-0. Moreover, 62% showed continued improvement in PASI response over time versus STRIDE week 12. In addition, approximately 80% reported pruritus Numerical Rating Scale <4 and 61% achieved Dermatology Life Quality Index 0/1. LIMITATIONS: This was an open-label study with limited sample size and no control. CONCLUSION: Envudeucitinib 40-mg twice daily in adults with moderate-to-severe plaque psoriasis demonstrated increasing and durable improvements in skin clearance and pruritus and was well-tolerated throughout 52 weeks of treatment.