Alumis' Oral Envudeucitinib Meets All Goals in Two Phase 3 Psoriasis Trials

Alumis said on January 6 that its oral drug envudeucitinib met all primary and secondary endpoints in two Phase 3 trials in adults with moderate-to-severe plaque psoriasis, according to the company's announcement, filed with the SEC. The results are company-reported topline data; Alumis said it plans to present more detailed results at a medical meeting.

Envudeucitinib is a twice-daily pill that selectively blocks tyrosine kinase 2 (TYK2), an enzyme involved in signaling by the inflammatory messengers IL-23, IL-17 and Type I interferon. The South San Francisco company said it plans to submit a New Drug Application to the US Food and Drug Administration in the second half of 2026.

The ONWARD trials

ONWARD1 and ONWARD2 were parallel, 24-week, randomized, double-blind trials that enrolled more than 1,700 patients in total. Patients were assigned in a 2:1:1 ratio to envudeucitinib 40 mg twice daily, placebo, or the active comparator apremilast. The co-primary endpoints, measured at week 16, were the share of patients achieving a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) and the share rated clear or almost clear on the static Physician's Global Assessment (sPGA 0/1).

In each trial, envudeucitinib beat placebo on both co-primary endpoints (p<0.0001), the company said. Averaged across the two trials, 74% of patients on the drug reached PASI 75 and 59% reached sPGA 0/1 at week 16. Alumis said the placebo-adjusted response rates were consistent between the trials.

At week 24, about 65% of patients reached PASI 90 and more than 40% reached PASI 100, meaning complete skin clearance, on average across both trials. Envudeucitinib also showed superior skin clearance compared with apremilast on all PASI endpoints at week 24 in each trial (p<0.0001), and separation from placebo on PASI 90 appeared as early as week 4, according to the release. The company did not give the placebo or apremilast response rates in its announcement.

Safety and what comes next

Alumis said envudeucitinib was generally well tolerated through week 24, with a safety profile consistent with its Phase 2 program. Most treatment-emergent adverse events were mild to moderate and transient; the most common were headaches, nasopharyngitis, upper respiratory tract infections and acne. The company said no new safety signals were observed.

"By maximally inhibiting TYK2, envudeucitinib blocks both IL-23 and IL-17 to deliver comprehensive disease control," said Jörn Drappa, Alumis's chief medical officer, in the release.

Patients who completed week 24 could enter ONWARD3, an ongoing long-term extension study of durability and safety. Alumis is also testing envudeucitinib in LUMUS, a Phase 2b trial in systemic lupus erythematosus, with topline data expected in the third quarter of 2026. Trade outlet Indian Pharma Post reported the same topline figures on January 8.