ONWARD: Oral Envudeucitinib Demonstrates High PASI Responses in Phase 3, With Andrew Blauvelt, MD

Phase 3 data for envudeucitinib — a next-generation, highly selective oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition — have demonstrated robust skin clearance in moderate-to-severe plaque psoriasis (PsO), in new data presented at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31.1,2

To discuss the findings, we spoke with Andrew Blauvelt, MD, MBA, Owner of Blauvelt Consulting, LLC, in Annapolis, Maryland, and a principal investigator on the ONWARD program, following his late-breaking oral presentation at the meeting. 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 74–75% of envudeucitinib-treated patients achieved PASI 75 and 59% achieved sPGA 0/1 — substantially higher than both placebo and apremilast. Blauvelt highlighted the week 24 data as particularly noteworthy: consistent with the class behavior of TYK2 inhibitors, response deepened over time, with approximately 80% achieving PASI 75, approximately 65% achieving PASI 90, and more than 40% achieving PASI 100 — complete clearance — by week 24. Envudeucitinib outperformed apremilast on all PASI endpoints at week 24 (P <.0001), and separation from placebo on PASI 90 was observed as early as week 4. Patient-reported quality-of-life and itch measures were consistent and clinically meaningful throughout.

On safety, the profile was favorable and consistent with phase 2 findings — the most common adverse events were nasopharyngitis and upper respiratory tract infection, with no major cardiovascular events, no tuberculosis reactivation, no clinically relevant hematologic or metabolic laboratory abnormalities, and notably no lipid signal of the kind observed in earlier deucravacitinib studies.

Blauvelt distinguished envudeucitinib from deucravacitinib as a second-generation TYK2 inhibitor specifically engineered for complete 24-hour target coverage — the only TYK2 inhibitor shown to achieve maximal inhibition over a full dosing interval in humans. An NDA submission is planned for the second half of 2026, with a once-daily extended-release formulation and a pediatric program both in development.

“[This was] a major reveal… phase 3 results for a new oral drug for psoriasis called envudeucitinib, next gen TYK2 inhibitor. If all goes well, if the FDA likes it… usually when phase 3 results are presented at AAD, oftentimes, we will see approval of the drug in the coming year,” Blauvelt said.

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 PlaceboControlled, Phase 3 ONWARD1 and 2 Studies. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31.

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