Envudeucitinib Outperforms Placebo and Apremilast in Phase 3 Psoriasis Trials

Key Takeaways

• Envudeucitinib demonstrated superior efficacy vs placebo and apremilast across multiple endpoints in Phase 3 ONWARD trials.
• High rates of skin clearance, including PASI-90 and PASI-100, were achieved by Week 24, with meaningful improvements in itch and scalp psoriasis.
• The TYK2 inhibitor was well tolerated, with a favorable safety profile and low rates of serious adverse events.

Envudeucitinib, a next-generation oral tyrosine kinase 2 (TYK2) inhibitor, demonstrated significant efficacy and a favorable safety profile in patients with moderate-to-severe plaque psoriasis, according to Phase 3 data from the ONWARD 1 and ONWARD 2 trials presented by Andrew Blauvelt, MD, MBA, at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

The randomized, double-blind studies enrolled more than 1,700 patients and compared envudeucitinib 40 mg twice daily with placebo through Week 16 and with apremilast through Week 24. Dr. Blauvelt emphasized the importance of the dataset, noting, “We don’t have very many Phase 3 reveals in our specialty. … This often leads to approval of drugs.” 

Envudeucitinib is designed as a selective, allosteric TYK2 inhibitor to avoid broader JAK1/2/3 inhibition.

“It has been specifically designed to be an allosteric inhibitor that's specific for TYK2 to avoid blockade of JAK1, JAK2, and JAK3,” Dr. Blauvelt said. 

At Week 16, both co-primary endpoints were met. PASI-75 responses were achieved in 76.5% and 70.4% of patients receiving envudeucitinib in ONWARD 1 and 2, respectively, compared with 18.7% and 13.7% for placebo (P < .0001). Similarly, sPGA 0/1 responses reached 61.0% and 57.3% vs 10.0% and 5.7% with placebo (P < .0001).

By Week 24, envudeucitinib demonstrated superiority over apremilast, with PASI-90 achieved in 68.0% and 62.1% of patients vs 25.6% in both trials (P < .0001). PASI-100 responses were also higher (41.0% and 39.5% vs 8.5% and 13.0%, respectively). Improvements extended to symptoms, with itch reductions significantly greater than placebo at Week 16 (least squares mean change −4.1 and −4.8 vs −0.9 and −1.6; P < .0001). Scalp psoriasis outcomes also favored envudeucitinib.

Dr. Blauvelt noted that the drug was engineered for sustained activity, with 24-hour coverage “to get complete blockade of TYK2 activity during the entire 24-hour period.” 

Safety findings were consistent across studies. Most treatment-emergent adverse events were mild to moderate, with headache, nasopharyngitis, acne, and upper respiratory tract infection among the most common. Serious adverse events were infrequent (2.7%) and largely unrelated to treatment, with no deaths or significant laboratory abnormalities reported.