Phase 3 ONWARD Data Position Envudeucitinib as High-Efficacy Oral TYK2 Inhibitor in Psoriasis

Late-breaking phase 3 data presented at the 2026 American Academy of Dermatology (AAD) Annual Meeting highlighted the clinical potential of envudeucitinib, an oral, next-generation TYK2 inhibitor, in moderate to severe plaque psoriasis. In an interview, Andrew Blauvelt, MD, dermatologist and owner of Blauvelt Consulting, LLC, described results from the ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738) trials, which evaluated envudeucitinib against placebo and active comparator apremilast.^1,2

Blauvelt described the agent as a mechanistically optimized successor within the TYK2 class. “Envudeucitinib is a TYK2 inhibitor. I call it a next-generation or second-generation TYK2 inhibitor,” he said, noting it was designed to achieve sustained pathway inhibition. “It could block TYK2 over an entire 24-hour period at maximal levels…a very efficient, very well-designed drug.”

Both studies enrolled adults with moderate to severe plaque psoriasis and utilized co-primary end points at week 16, including a Psoriasis Area and Severity Index (PASI) 75 score and Physician’s Global Assessment (PGA) 0/1. According to Blauvelt, the trials met all primary end points with clinically meaningful separation from comparators. “At week 16, about 75% of the patients had PASI 75,” he reported, with substantially lower response rates observed with apremilast and placebo.

Efficacy continued to improve through week 24, consistent with the delayed maximal response often observed with IL-23–axis modulation. Blauvelt highlighted that, “Patients got up to about 80% PASI 75, about 65% PASI 90, and 40% of patients achieved PASI 100.” He emphasized the clinical relevance of these findings, adding, “It’s pretty impressive to see an oral drug with 40% of the patients achieving complete clearance.”

Safety findings were favorable and consistent with prior TYK2 data. “There were no major issues—the drug actually looked very safe,” Blauvelt stated. The most common adverse events included nasopharyngitis and upper respiratory tract infections. Notably, there were no signals for serious adverse events such as major adverse cardiovascular events, tuberculosis reactivation, or laboratory abnormalities, including lipid elevations—an area of prior scrutiny within the class.

From a development perspective, Blauvelt suggested that regulatory progress may follow typical timelines for late-breaking phase 3 dermatology data. “Usually when phase 3 results are presented at the AAD, oftentimes, we will see approval of the drug in the coming year. So, that's the expected time when this drug may get to the market,” he said.

Future directions include formulation optimization and broader population studies. The agent is currently dosed at 40 mg twice daily, but “the company is already working on a long-release tablet…to get to a single pill, once a day,” Blauvelt noted. Pediatric studies are also planned.

Collectively, the ONWARD program positions envudeucitinib as a potentially high-efficacy oral alternative in psoriasis, with PASI 90/100 rates approaching those of biologic therapies while maintaining a favorable safety profile.

References

1. Blauvelt A. Envudeucitinib (ESK-001) in moderate-to-severe plaque psoriasis: 24-week results from the randomized, double-blind, active comparator- and placebo-controlled, phase 3 ONWARD 1 and 2 studies. Presented at: 2026 American Academy of Dermatology Annual Meeting; March 27-30, 2026; Denver, CO.
2. Alumis’ envudeucitinib delivers early and robust improvements in skin clearance, quality of life, and psoriasis symptoms in two phase 3 trials, underscoring its potential as a leading oral therapy for plaque psoriasis. News release. Alumis. March 28, 2026. Accessed March 31, 2026. https://investors.alumis.com/news-releases/news-release-details/alumis-envudeucitinib-delivers-early-and-robust-improvements