Oral TYK2 Inhibitor Followed for 48 Weeks: More Than Half of Patients Achieve Complete Psoriasis Skin Clearance

For patients with moderate-to-severe plaque psoriasis, an oral drug that delivers both deep clearance and durable efficacy could address the needs of those for whom topical treatments are insufficient and who are unwilling or unable to use injectable biologics. Alumis announced that in the Phase 3 long-term extension trial ONWARD3, 54% of the 773 patients who had continuously received envudeucitinib since the start of the parent trials achieved complete skin clearance after 48 weeks of treatment.

This endpoint, known as PASI 100, means that a patient’s Psoriasis Area and Severity Index improved by 100% from before treatment. Among the same continuously treated patients, PASI 100 rates at Week 24 in the two parent trials, ONWARD1 and ONWARD2, were 41.0% and 39.5%, respectively. The extension trial results therefore suggest that some patients’ responses may continue to deepen after six months, rather than merely maintaining the early effect.

envudeucitinib, formerly known as ESK-001, is an allosteric TYK2 inhibitor taken orally twice daily. TYK2 is involved in immune signaling by IL-23, IL-17, and type I interferons, pathways closely associated with inflammation in psoriasis. The drug targets TYK2’s regulatory region rather than directly occupying the catalytic ATP-binding site. Its development aims to suppress disease-causing signals while reducing the unintended effects that may arise from broader JAK inhibition.

ONWARD1 and ONWARD2 enrolled more than 1,700 adults in total and used randomized, double-blind designs, with placebo and the oral drug apremilast as comparators. Participants who completed 24 weeks of treatment could enter ONWARD3. Clinical trial registry information indicates that ONWARD3 includes open-label and blinded treatment phases and is intended not only to track efficacy, but also to assess maintenance of response, changes after treatment discontinuation, and long-term safety.

Alumis said that no new safety signals were identified through 48 weeks of cumulative treatment. However, the current data remain preliminary results announced by the company. Complete details on adverse-event frequencies, serious infections, discontinuation rates, and the various analysis populations have not yet been provided, and the results have not undergone peer review. Patients who were able to continue treatment and complete assessments in the extension trial may also differ from the overall population initially randomized, so the 54% figure cannot be directly regarded as the expected one-year outcome for all patients taking the drug.

The company said this is currently the highest PASI 100 rate among oral psoriasis therapies, but enrollment criteria, handling of missing data, and assessment timing differ across drug trials, so cross-trial rankings cannot replace head-to-head comparisons. Alumis plans to submit a new drug application to the U.S. Food and Drug Administration in the fourth quarter of 2026. A key issue in the regulatory review will be whether the complete data can simultaneously support deep clearance, durability of efficacy, and the safety boundaries required for chronic treatment.