Alumis files NDA plan for envudeucitinib after Phase 3 psoriasis data

Alumis has presented new Phase 3 data from its ONWARD programme for envudeucitinib, an investigational oral TYK2 inhibitor, in moderate-to-severe plaque psoriasis, with results spanning scalp clearance, itch relief, and quality-of-life outcomes. The company said a New Drug Application submission to the US Food and Drug Administration remains on track for the fourth quarter of 2026.

The headline efficacy figure is a 54% PASI 100 response rate at Week 48 in ONWARD3, which Alumis describes as the highest publicly reported complete skin clearance rate among oral psoriasis therapies, whether approved or investigational. The company said this claim has not been independently verified in a head-to-head trial; it represents a cross-trial comparison against published benchmarks, which carries inherent limitations.

What the data showed

Beyond the skin clearance primary endpoint, the new analyses focused on secondary measures. In ONWARD1 and ONWARD2, roughly one-third of patients achieved clinically meaningful itch reduction within two weeks of starting treatment. By Week 16, approximately 40% had reached complete itch resolution and around 60% reported minimal or no itch. In the long-term extension study ONWARD3, nearly 80% of patients sustained meaningful itch reduction through Week 48.

Scalp disease, which is notoriously difficult to manage and carries a disproportionate impact on patient quality of life, showed similarly durable results. More than 80% of ONWARD3 participants maintained clear or near-clear scalp skin at 48 weeks, as measured by the scalp-specific Physician Global Assessment. On quality-of-life outcomes, around half of patients in ONWARD1 and ONWARD2 reached a Dermatology Life Quality Index score of 0 or 1 by Week 12, with more than 70% sustaining that threshold in ONWARD3. Patients who switched from placebo or from apremilast caught up to continuous-treatment arms by Week 48.

Treatment was generally well tolerated, with no new safety signals identified during long-term exposure in ONWARD3. The ONWARD programme enrolled more than 1,700 patients across ONWARD1 and ONWARD2, with ONWARD3 designed to provide up to 96 weeks of long-term safety and efficacy data.

Mark Lebwohl, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai, said the "consistency of these findings across the ONWARD3 program, alongside high-threshold skin clearance and a favorable tolerability profile, is highly encouraging and underscores the clinical relevance of targeted TYK2 inhibition designed for maximal 24-hour target coverage."

Market context and competitive positioning

The oral psoriasis market is undergoing significant transformation. BMS's deucravacitinib (Sotyktu), the only approved selective TYK2 inhibitor for plaque psoriasis, became the benchmark for the oral category when it received FDA approval in 2022. Alumis is positioning envudeucitinib as a next-generation successor, citing its allosteric mechanism and what it describes as maximal 24-hour TYK2 target inhibition, a pharmacodynamic claim the company says is supported by human data. Whether that translates into a clinically or commercially meaningful advantage over deucravacitinib will depend partly on label wording and partly on how payers and prescribers interpret cross-trial comparisons in the absence of a direct head-to-head study.

The broader oral immunology space is crowded. JAK inhibitors such as upadacitinib and abrocitinib have established a high bar in atopic dermatitis, and several are being evaluated in psoriasis. Biologics targeting IL-17 and IL-23 pathways continue to dominate the moderate-to-severe market, though their injectable delivery remains a differentiator in favour of oral options among patients who are needle-averse or whose disease is inadequately controlled on existing oral therapies.

Alumis also has envudeucitinib in development for systemic lupus erythematosus, and a separate TYK2 inhibitor, A-005, is being explored in neuroinflammatory indications. Regulatory acceptance of the NDA filing, expected in Q4 2026, will be the next major catalyst for the company.