Envudeucitinib Provides Rapid and Sustained Itch Relief, Including Complete Itch Resolution, in Patients with Moderate-to-Severe Plaque Psoriasis: 24 Week Results from the Phase 3 ONWARD 1 and ONWARD2 Trials

Background: Itch is one of the most burdensome symptoms of plaque psoriasis and substantially impairs sleep, quality of life, productivity and daily functioning. Although skin clearance has improved with novel psoriasis therapies, itch relief remains an important unmet need, particularly among patients with uncontrolled itch or clinically significant scalp involvement. Envudeucitinib (ESK-001), an investigational highly selective oral next-generation TYK2 inhibitor, has demonstrated high skin clearance in patients with moderate-to-severe plaque psoriasis in the replicate Phase 3 ONWARD1 and 2 trials.1 This analysis evaluates the onset, magnitude, and durability of itch improvement with envudeucitinib, including patients with scalp involvement. Methods: Worst itch was assessed using a self-administered Numeric Rating Scale (NRS, 0–10), reflecting worst itch over the prior 24 hours. Endpoints assessed included the proportion of patients who achieved a ≥4-point improvement from baseline among those with a baseline NRS ≥4 (N1=704, N2=695), NRS 0/1 and NRS 0 (among those with baseline NRS ≥1; N1=840, N2=799), and a ≥4-point improvement in patients with baseline scalp-specific Physician's Global Assessment (ss-PGA) ≥3 and baseline NRS ≥4 (N1=439, N2=461). Non-responder imputation was applied across all endpoints. Results: Clinically meaningful ≥4-point itch improvement was achieved as early as Week 2 by 34.9% and 33.3% of patients treated with envudeucitinib in ONWARD1 and 2, respectively. By Week 16, over one-third of patients treated with envudeucitinib achieved complete itch resolution (NRS 0), with 35.0% and 36.3% of patients in ONWARD1 and ONWARD2, respectively, compared with 6.7% and 4.5% receiving placebo, and 13.3% and 18.1% receiving apremilast (all nominal p<0.0001). NRS 0/1 was achieved by 57.4% and 54.8% of patients treated with envudeucitinib vs 14.3% and 12.5% with placebo, and 36.2% and 32.2% with apremilast (all nominal p<0.0001). At Week 24, achievement of ≥4-point NRS improvement continued to increase and was reported by 73.7% and 74.5% of patients treated with envudeucitinib in ONWARD1 and ONWARD2, respectively, vs 53.4% and 48.2% with apremilast (both nominal p<0.0001). Comparable itch improvements were also observed among patients with clinically significant scalp involvement. Among these patients, a ≥4-point improvement in NRS overall was achieved by 33.3% and 31.4% of patients treated with envudeucitinib in ONWARD1 and ONWARD2 as early as Week 2. By Week 16, 72.3% and 67.5% experienced a ≥4-point improvement vs 15.7% and 19.7% with placebo, and 50.8% and 44.4% with apremilast; and by Week 24, 75.1% and 72.7% vs 48.4% and 48.1% with apremilast (all p<0.0001). Conclusion: Treatment with envudeucitinib resulted in rapid and sustained itch relief in patients with moderate-to-severe plaque psoriasis and clinically significant baseline itch, including those with baseline scalp involvement. Consistent results across two independent Phase 3 studies demonstrate that itch relief was evident as early as Week 2 and continued to improve through Week 24.