Envudeucitinib Achieves 54% PASI 100 Rate at 48 Weeks in Phase 3 Extension

Alumis Inc. reported topline results from the ongoing ONWARD3 long-term extension study showing that envudeucitinib, an investigational oral tyrosine kinase 2 (TYK2) inhibitor, achieved complete skin clearance in 54% of continuously treated patients at 48 weeks.¹ Alumis described the result as the highest reported PASI 100 response rate among existing and investigational oral therapies for psoriasis.¹

The company announced the findings August 10, 2026, and remains on track to submit a new drug application (NDA) to the FDA in the fourth quarter of 2026 for the treatment of moderate-to-severe plaque psoriasis.¹

The long-term findings extend results from the phase 3 ONWARD1 and ONWARD2 trials and provide additional data on the durability of response and longer-term safety of envudeucitinib. Plaque psoriasis affects more than 8 million adults in the United States, and approximately 1 in 4 patients has moderate-to-severe disease based on quality-of-life impact and body surface area involvement.¹

ONWARD Phase 3 Program

The phase 3 ONWARD clinical program includes 2 parallel, global, multicenter, randomized, double-blind, placebo- and active-comparator-controlled trials: ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738). More than 1700 adults with moderate to severe plaque psoriasis were enrolled and randomized 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or apremilast for 24 weeks.¹

Patients who completed week 24 of either trial were eligible to enter ONWARD3 (NCT06846541), an ongoing long-term extension evaluating durability, maintenance of response, and long-term safety. All patients entering ONWARD3 received open-label envudeucitinib during the first 24 weeks of the extension, regardless of their original treatment assignment. The study is designed to provide up to 96 weeks of long-term safety and efficacy data.^1,2

A total of 1509 patients entered ONWARD3 from ONWARD1 or ONWARD2, representing a rollover rate of more than 85%.¹

PASI 90 and Complete Skin Clearance at 48 Weeks

A nonresponder imputation analysis included 773 patients from the envudeucitinib arms who received up to 48 weeks of continuous treatment—24 weeks in ONWARD1 or ONWARD2 followed by up to 24 weeks in ONWARD3. At 48 weeks, 75% achieved PASI 90 and 54% achieved PASI 100.¹

Alumis also reported a separate integrated nonresponder imputation analysis of 890 patients originally randomized to envudeucitinib in ONWARD1 or ONWARD2, including patients who did not transition into ONWARD3. In that broader population, 66% achieved PASI 90 and 47% achieved PASI 100 after 48 weeks of treatment.¹

The distinction between the analyses is important: the 54% PASI 100 result reflects patients from the envudeucitinib arms who continued into ONWARD3, whereas the integrated analysis incorporates the original randomized population, including patients who did not transition into the extension.

Skin Clearance Responses Remained Durable

Among patients who entered ONWARD3 with PASI 90 and PASI 100 responses, approximately 90% and 80%, respectively, maintained those levels of skin clearance for the reported duration of the extension study.¹ Alumis also reported that the proportion of patients achieving complete skin clearance continued to increase over time.

To further assess durability and maintenance of response, the first 200 patients who achieved PASI 75 at week 24 of ONWARD3 were eligible to enter a 24-week randomized withdrawal period. Participants were randomized to blinded envudeucitinib or placebo and returned to open-label envudeucitinib upon loss of response or completion of the withdrawal period, whichever occurred first.^1,2

Safety Remained Consistent Through Long-Term Treatment

Envudeucitinib continued to be well tolerated in ONWARD3, with a safety profile consistent with findings from ONWARD1 and ONWARD2 and no new safety signals observed, according to Alumis.¹ The investigational therapy is an oral allosteric TYK2 inhibitor designed to provide sustained target inhibition and can be administered with or without food, with no fasting requirement.¹

Mark Lebwohl, MD, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, said the phase 3 program demonstrated consistently high levels of skin clearance, with responses maintained through 48 weeks and complete clearance rates continuing to increase.

These data, coupled with a consistent safety profile, suggest that envudeucitinib can deliver the durable, reliable disease control physicians and patients are seeking from an oral therapy, — Mark Lebwohl, MD,¹

NDA Submission Planned for Late 2026

Alumis plans to present additional ONWARD program results at upcoming medical meetings and submit an NDA to the FDA in the fourth quarter of 2026 seeking approval of envudeucitinib for moderate-to-severe plaque psoriasis.¹

Beyond psoriasis, envudeucitinib is being evaluated in systemic lupus erythematosus in the potentially pivotal phase 2b LUMUS trial, with topline results expected in the third quarter of 2026. The drug is designed to selectively inhibit TYK2-mediated signaling involved in IL-23, IL-17, and type I interferon pathways implicated across multiple immune-mediated diseases.¹

References

1. Envudeucitinib long-term data positioned to set a new standard for plaque psoriasis treatment, delivering highest reported PASI 100 skin clearance among oral therapies. News release. Alumis Inc. August 10, 2026. Accessed August 11, 2026. https://investors.alumis.com/news-releases/news-release-details/envudeucitinib-long-term-data-positioned-set-new-standard-plaque
2. A study to assess the long-term safety and efficacy of envudeucitinib in adult participants with moderate to severe chronic plaque psoriasis (ONWARD3). ClinicalTrials.gov. NCT06846541. Accessed August 11, 2026. https://clinicaltrials.gov/study/NCT06846541