Alumis reports 48-week Phase 3 data for envudeucitinib, showing 54% PASI 100 and sustained improvements in plaque psoriasis symptoms.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Alumis reported 48-week data from its ONWARD Phase 3 program showing that envudeucitinib achieved complete skin clearance in 54% of patients with moderate-to-severe plaque psoriasis. Additional findings showed sustained improvements in scalp disease, itch and quality of life, as the company prepares a US regulatory submission in the fourth quarter of 2026.
Sustained Skin Clearance and Symptom Relief
The results, presented at the 26th Annual Fall Clinical Dermatology Conference, extend findings from ONWARD1, ONWARD2 and the long-term extension study ONWARD3. Alumis described the 54% PASI 100 response rate at Week 48 as the highest publicly reported for an oral psoriasis therapy, including investigational treatments.
PASI 100 represents complete clearance of psoriasis lesions according to the Psoriasis Area and Severity Index. The findings also highlighted improvements in difficult-to-treat scalp disease and reductions in itching, which can substantially affect patients’ daily lives.
More than 80% of patients in ONWARD3 maintained clear or almost clear scalp skin at Week 48, measured using the scalp-specific Physician Global Assessment (ss-PGA) score of 0 or 1.
In ONWARD1 and ONWARD2, approximately one-third of patients achieved a clinically meaningful reduction in itch, defined as an improvement of at least four points on the numerical rating scale (NRS), by Week 2. By Week 16, approximately 40% reported complete itch resolution (NRS 0), while around 60% reported minimal or no itch (NRS 0/1). Nearly 80% of patients in ONWARD3 sustained clinically meaningful itch reductions through Week 48.
Quality-of-life measures also improved. Approximately 50% of patients in ONWARD1 and ONWARD2 achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1 by Week 12, indicating minimal or no effect of psoriasis on daily life. More than 70% maintained these scores at Week 48 in ONWARD3.
Phase 3 Program and Safety
ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738) enrolled more than 1,700 adults with moderate-to-severe plaque psoriasis. Both were randomized, double-blind, 24-week trials comparing oral envudeucitinib 40 mg twice daily with placebo and apremilast, an established oral psoriasis treatment.
Patients completing Week 24 could enter ONWARD3 (NCT06846541), an ongoing long-term extension study. Participants received open-label envudeucitinib for its initial 24 weeks, regardless of their original treatment assignment. The first 200 patients achieving PASI 75 at Week 24 of ONWARD3 could enter a 24-week randomized withdrawal period, receiving blinded envudeucitinib or placebo. Patients could return to open-label treatment following loss of response or completion of the withdrawal period.
Patients switching from placebo or apremilast showed rapid improvements across primary and key secondary endpoints, reaching outcomes comparable to those of patients receiving continuous treatment by Week 48.
Treatment was generally well tolerated, and Alumis reported no new safety signals with longer-term exposure in ONWARD3. The company did not provide detailed adverse-event rates in the announcement.
TYK2 Inhibition and Regulatory Outlook
Envudeucitinib is an investigational oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2). The enzyme regulates immune-signaling pathways, including interleukin-23 and type I interferon signaling, that contribute to inflammatory diseases such as psoriasis. Alumis reports that the drug maintains target inhibition over 24 hours while minimizing off-target activity.
The company is preparing to submit a New Drug Application (NDA) to the US Food and Drug Administration in the fourth quarter of 2026. If approved, envudeucitinib would compete in the oral systemic treatment market for moderate-to-severe plaque psoriasis.
The latest findings add longer-term evidence on skin clearance, symptom control and quality of life. However, envudeucitinib remains investigational, and its eventual clinical role will depend on regulatory review and the totality of efficacy and safety data.
Reference
Alumis Announces New Phase 3 Data Demonstrating Envudeucitinib Rapidly and Durably Improved Psoriasis Burden Across Scalp, Itch, and Quality of Life Measures, Alumis, 09 October 2026
A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients with Moderate to Severe Plaque Psoriasis (ONWARD1), ClinicalTrials.gov ID NCT06586112
A Study in Patients with Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (ONWARD2), ClinicalTrials.gov ID NCT06588738
Long-term Safety and Efficacy of ESK-001 in Moderate to Severe Plaque Psoriasis (ONWARD3), ClinicalTrials.gov ID NCT06846541
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.