How Envudeucitinib May Fit Into the Evolving Oral Psoriasis Landscape, With Andrew Blauvelt, MD, MBA

The 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31, marked a watershed moment for the oral psoriasis treatment landscape, with late-breaking phase 3 data presented for 2 next-generation TYK2 inhibitors — envudeucitinib and zasocitinib — arriving just weeks after the FDA approval of icotrokinra (Icotyde), the first oral IL-23 receptor antagonist approved for moderate to severe plaque psoriasis. Andrew Blauvelt, MD, MBA, owner of Blauvelt Consulting, in Annapolis, Maryland, and a principal investigator on the ONWARD program, spoke about where envudeucitinib fits in the context of this rapidly expanding field.

Blauvelt characterized envudeucitinib as a second-generation TYK2 inhibitor specifically engineered for complete 24-hour target coverage — distinct from the first approved agent in the class, deucravacitinib — and the only TYK2 inhibitor to date shown to achieve maximal inhibition over a full dosing interval in humans. The ONWARD1 and ONWARD2 trials together enrolled more than 1,700 adults with moderate to severe plaque psoriasis, randomized 2:1:1 to envudeucitinib 40 mg twice daily, placebo, or the active comparator apremilast, with co-primary endpoints of PASI 75 and static Physician's Global Assessment (sPGA) 0/1 at week 16. Both studies met all primary and secondary endpoints with high statistical significance versus placebo (P <.0001). At week 16, approximately 74% to 75% of envudeucitinib-treated patients achieved PASI 75 and 59% achieved sPGA 0/1. Response continued to deepen through week 24, at which point approximately 80% achieved PASI 75, approximately 65% achieved PASI 90, and more than 40% achieved PASI 100 — complete skin clearance. Envudeucitinib outperformed apremilast on all PASI endpoints at week 24 (P <.0001), with separation from placebo on PASI 90 observed as early as week 4. The safety profile was favorable and consistent with phase 2 findings, with nasopharyngitis and upper respiratory tract infection the most common adverse events and notably no lipid signal of the type observed in earlier deucravacitinib studies.

Zasocitinib, Takeda's once-daily investigational TYK2 inhibitor, presented concurrent phase 3 data from the LATITUDE PsO 3001 and 3002 trials at the same meeting. In those studies, 71.4% and 69.2% of zasocitinib-treated patients achieved sPGA 0/1 at week 16 versus 10.7% and 12.6% with placebo (P <.001), with PASI 75 responses observed as early as week 4 and more than 90% of week 40 responders maintaining response through week 60. Also arriving just before AAD, icotrokinra received FDA approval on March 18, 2026 as the first targeted oral peptide to precisely block the IL-23 receptor, with approval based on the phase 3 ICONIC program in approximately 2,500 patients. In the ICONIC-ADVANCE head-to-head studies, approximately 70% of patients achieved IGA 0/1 and 55% achieved PASI 90 at week 16, with icotrokinra demonstrating superiority over deucravacitinib at weeks 16 and 24.

Blauvelt placed these 3 agents in direct relation to one another, noting that the best IL-23 and IL-17 biologics likely still represent the ceiling for skin clearance. For patients prioritizing maximum efficacy, he would continue to favor those agents; however, for the many patients who prefer oral therapy and the many clinicians who remain reluctant to prescribe biologics, he characterized icotrokinra, envudeucitinib, and zasocitinib as agents that will move immediately to the top of the oral treatment hierarchy. He noted that dosing may be an early point of practical differentiation — zasocitinib and icotrokinra are once daily, while envudeucitinib is currently dosed twice daily, though Alumis has indicated plans to develop an extended-release once-daily formulation. He also raised the possibility that performance in psoriatic arthritis could ultimately drive prescribing choices among these agents if data reveal meaningful differences in joint outcomes. An NDA submission for envudeucitinib is planned for the second half of 2026.

Blauvelt’s disclosures include Abbvie, Almirall, Alumis, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis Biotherapeutics, Eli Lilly, Incyte, Janssen, LEO Pharma, Lipidio Pharma, Novartis, Oruka Therapeutics, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharma, Takeda, and UCB.

References

1. Blauvelt A, Sofen H, Armstrong A, et al. Envudeucitinib (ESK-001) in moderate-to-severe plaque psoriasis: 24-week results from the randomized, double-blind, active comparator- and placebo-controlled, phase 3 ONWARD1 and 2 studies. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

2. Alumis Inc. 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. Press release. March 28, 2026. Accessed March 28, 2026. https://investors.alumis.com/news-releases/news-release-details/alumis-envudeucitinib-delivers-early-and-robust-improvements

3. Gooderham M, et al. Once-daily oral zasocitinib demonstrates rapid and reproducible skin clearance with a consistent safety profile in moderate-to-severe plaque psoriasis: results from two randomized phase 3 trials (LATITUDE-PsO-3001 and 3002). Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

4. Johnson & Johnson. FDA approval of ICOTYDE™ (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. Press release. March 18, 2026. Accessed March 28, 2026. https://www.investor.jnj.com/investor-news/news-details/2026/FDA-approval-of-ICOTYDE-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide/default.aspx