Envudeucitinib Shows Durable Skin Clearance in Phase 3 Psoriasis Extension

For dermatology nurse practitioners (NPs) and physician associates (PAs) treating plaque psoriasis, the oral treatment landscape could continue to expand.

Envudeucitinib, an investigational oral tyrosine kinase 2 (TYK2) inhibitor, achieved complete skin clearance in 54% of continuously treated patients at 48 weeks in the ongoing phase 3 ONWARD3 long-term extension study, according to topline results announced by Alumis Inc.1 The company described the result as the highest reported PASI 100 response rate among existing and investigational oral psoriasis therapies.¹

Beyond the headline number, the findings provide a longer look at whether the skin clearance achieved with envudeucitinib can continue, or even improve, with extended treatment.

What Did the ONWARD Program Study?

The phase 3 ONWARD program began with ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738), 2 parallel global trials enrolling more than 1700 adults with moderate to severe plaque psoriasis. Participants were randomized 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or apremilast for 24 weeks.¹

Patients completing week 24 could enter ONWARD3 (NCT06846541), an ongoing long-term extension evaluating the durability, maintenance, and longer-term safety of envudeucitinib. More than 85% of eligible patients rolled over into the extension.¹

All participants entering ONWARD3 received open-label envudeucitinib during the first 24 weeks of the extension, regardless of their original treatment assignment.

Skin Clearance Continued to Improve

Among 773 patients who received envudeucitinib continuously for up to 48 weeks, 75% achieved PASI 90 and 54% achieved PASI 100 using nonresponder imputation.¹

Those findings build on the earlier ONWARD1 and ONWARD2 results. At week 24, PASI 100 responses were 41.0% and 39.5% in the respective trials, suggesting that some patients continued to gain skin clearance with longer treatment.²

For clinicians, that trajectory may be particularly relevant when discussing treatment expectations with patients. Psoriasis therapies are not always at their maximum benefit during the first several months, and the extension findings suggest complete clearance with envudeucitinib may continue to increase beyond the initial 24-week treatment period.

MORE ON PSORIASIS

Why the 54% Figure Needs Context

The 54% PASI 100 result does not represent every patient originally randomized to envudeucitinib.

It reflects patients from the envudeucitinib treatment arms who continued into ONWARD3. Alumis separately analyzed 890 patients originally randomized to envudeucitinib in ONWARD1 and ONWARD2, including those who did not transition into the extension. In that broader population, PASI 90 and PASI 100 rates at 48 weeks were 66% and 47%, respectively.¹

That distinction is important when interpreting long-term extension data, as patients who continue into extension studies may differ from those who do not.

Still, both analyses showed substantial levels of skin clearance with longer-term treatment.

Responses Appeared Durable

Achieving clear or nearly clear skin is one goal; maintaining it is another.

Among patients entering ONWARD3 who had already achieved PASI 90, approximately 90% maintained that response during the reported extension period. Approximately 80% of patients entering with PASI 100 maintained complete skin clearance.¹

ONWARD3 also includes a randomized withdrawal component designed to further examine durability. The first 200 eligible patients achieving PASI 75 at week 24 of the extension could enter a 24-week withdrawal period and receive blinded envudeucitinib or placebo. Patients returned to open-label treatment following loss of response or completion of the withdrawal period.¹

These data may eventually help clinicians better understand what happens when treatment is interrupted and how dependent sustained disease control is on continued therapy.

Where Could Envudeucitinib Fit in Practice?

If approved, envudeucitinib could add another oral option for patients with moderate to severe plaque psoriasis.

The drug is a highly selective, oral allosteric TYK2 inhibitor designed to inhibit signaling associated with inflammatory pathways including IL-23, IL-17, and type I interferons.¹ Unlike some oral therapies that require specific administration considerations, envudeucitinib can be taken with or without food and does not require fasting.¹

For NP/PAs who frequently manage long-term psoriasis treatment, another effective oral option could be particularly relevant for patients who prefer pills over injections, are hesitant to initiate biologic therapy, or need alternatives after inadequate response to previous treatment.

Importantly, envudeucitinib remains investigational, and its ultimate role in treatment algorithms will depend on the complete efficacy and safety data, regulatory review, labeling, and how its profile compares with established oral and biologic therapies.

What About Longer-Term Safety?

No new safety signals were reported in the ONWARD3 topline findings, and Alumis stated that the longer-term safety profile remained consistent with observations from ONWARD1 and ONWARD2.¹

The extension study is designed to provide up to 96 weeks of long-term safety and efficacy data, making continued follow-up important as the program progresses.

For APPs, those longer-term findings may be especially relevant when considering how a potential new TYK2 inhibitor could fit into chronic psoriasis management, where treatment decisions extend well beyond initial skin clearance.

What Comes Next?

Alumis plans to submit a new drug application to the FDA in the fourth quarter of 2026 seeking approval of envudeucitinib for moderate to severe plaque psoriasis.¹

Additional ONWARD data are also expected to be presented at future medical meetings.

Envudeucitinib is being studied beyond psoriasis as well. The drug is under investigation in systemic lupus erythematosus in the phase 2b LUMUS trial, reflecting broader interest in selective TYK2 inhibition across immune-mediated diseases.

For dermatology NP/PAs, the upcoming regulatory review will be worth watching. If approved, envudeucitinib could further expand the conversation around how clinicians balance efficacy, safety, convenience, and patient preference when choosing between oral and injectable systemic treatments for psoriasis.

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