ONWARD Studies: Oral Envudeucitinib Treatment Effective, Safe for Psoriasis

Oral envudeucitinib therapy is both safe and effective for adults with moderate-to-severe plaque psoriasis, new data suggest, with all of its primary and secondary endpoints being met in 2 recent studies.1

This January announcement by Alumis Inc. highlighted these positive topline results from the company’s phase 3 ONWARD1 and ONWARD2 studies assessing the use of envudeucitinib in adults with psoriasis. The chronic inflammatory disease is known to be driven by abnormal immune signaling, especially involving the interleukin (IL)-23 and IL-17 pathways, and it impacts more than 8 million US adults.

“Patients with moderate-to-severe psoriasis have to choose between oral and biologic therapies,” Andrew Blauvelt, MD, from Blauvelt Consulting in Annapolis, said in a statement.1 “And for individuals seeking the best chance for clearance, biologics have long been superior to oral therapies. But now, with these new data on envudeucitinib, we’re seeing an exciting possibility of a new oral drug for psoriasis that can deliver high levels of efficacy in a safe manner.”

According to the National Psoriasis Foundation, roughly 25% of patients with psoriasis have moderate-to-severe disease when their condition is evaluated by its level of body surface area involvement and by quality-of-life impacts.2 Envudeucitinib, intended to address immune dysregulation across diseases driven by various proinflammatory mediators, was designed as a highly selective, oral, allosteric TYK2 inhibitor.

To evaluate this drug among adults with psoriasis, the phase 3 ONWARD program was conducted, consisting of 2 global, randomized, double-blind, placebo- and active-comparator–controlled trials: ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738). Each study took place over a period of 24 weeks.1

Across both ONWARD1 and ONWARD2, their respective investigative teams randomized 1700 adult patients with moderate-to-severe psoriasis in a 2:1:1 ratio to be provided with envudeucitinib 40 mg twice daily, placebo, or apremilast. The studies’ co-primary endpoints were attainment of 75% or greater Psoriasis Area and Severity Index score improvement (PASI 75) and a static Physician’s Global Assessment (sPGA) of 0/1 at the 16-week mark compared with placebo.

Participants who finished the 24 weeks of the analysis were deemed by the investigators to be eligible to enter the long-term ONWARD3 extension study. Overall, envudeucitinib met all of the primary and secondary endpoints in both of these trials, with the team observing a strong level of statistical significance. By the 16-week mark, the medication demonstrated superior efficacy versus placebo for achievement of both PASI 75 and sPGA 0/1 (P < .0001).1

On average across ONWARD1 and ONWARD2, the investigators also found 74% of those evaluated attained a PASI 75 score and 59% achieved sPGA 0/1. Responses also continued to improve over the course of time. Consistency in their placebo-adjusted response rates was also noted between the 2 analyses.

Approximately 65% of participants achieved PASI 90 by the 24-week mark. ONWARD investigators also concluded more than 40% of subjects achieved complete disease clearance (PASI 100) across both of the studies. Observed separation from placebo on PASI 90 scores was noted as early as the 4-week mark. Envudeucitinib outperformed apremilast on all of these studies’ PASI endpoints at Week 24 in both ONWARD1 and ONWARD2 (P < .0001).1 Patient-reported quality-of-life and itch measures were also found to have been consistent and clinically meaningful.

Through Week 24, the drug was generally shown to be well-tolerated among those treated. The investigative team noted consistency between envudeucitinib’s safety profile and earlier phase 2 and long-term extension findings. No new safety concerns were identified. Most treatment-emergent adverse events (TEAEs) were observed to be mild to moderate, manageable, and transient. The most common TEAEs were nasopharyngitis, headache, acne, and upper respiratory tract infection.

Alumis noted its plan to share additional ONWARD1 and ONWARD2 data at an upcoming scientific meeting and to submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) in the second half of the year.

“These pivotal data strengthen our conviction in envudeucitinib’s potential to transform the treatment landscape for IL‑23/IL‑17–driven diseases as well as those driven by Type I interferon,” Martin Babler, Chief Executive Officer of Alumis, said in a statement.1 “These results reinforce our enthusiasm that envudeucitinib’s highly differentiated clinical profile positions it at the forefront of next-generation TYK2 inhibitors in psoriasis, with potential in systemic lupus erythematosus and beyond as a true pipeline-in-a-pill.”

References

1. Alumis’ Envudeucitinib Delivers Leading Skin Clearance Among Next-Generation Oral Plaque Psoriasis Therapies in Phase 3 Program. Alumis Inc. January 6, 2026. https://www.globenewswire.com/news-release/2026/01/06/3213465/0/en/Alumis-Envudeucitinib-Delivers-Leading-Skin-Clearance-Among-Next-Generation-Oral-Plaque-Psoriasis-Therapies-in-Phase-3-Program.html.

2. NPF Issues Position Statement on Psoriasis Severity and Access to Care. National Psoriasis Foundation. December 30, 2025. https://www.psoriasis.org/position-statement-on-psoriasis-severity/#:~:text=We%20are%20saying%20that%20there,treat%20inflammation%20throughout%20the%20body.