Zasocitinib Outperforms Deucravacitinib in Plaque Psoriasis Trial

In the first head-to-head trial comparing two oral tyrosine kinase 2 (TYK2) inhibitors for plaque psoriasis, zasocitinib proved 2.5 times more effective than deucravacitinib (Sotyktu) at achieving the highest bar of efficacy at week 16, Medscape Medical News reported.

Zasocitinib Bests Deucravacitinib in Phase 3 Trial Results

Researchers presented the findings from the LATITUDE Atlas study during a late-breaker session at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna. The primary endpoint of a Psoriasis Area and Severity Index (PASI) 100 score—indicating psoriatic skin completely free of erythema, induration, infiltration, and scaling—was reached by 36.5% of the 301 patients treated with once-daily zasocitinib 30 mg. By comparison, 13.9% of the 303 patients treated with once-daily deucravacitinib 6 mg achieved the same benchmark, yielding a statistically significant difference of P < .001.

Key secondary endpoints also favored the investigational therapy. An absolute PASI score of 2 or lower was achieved by 66.1% of patients in the zasocitinib group versus 38.0% in the deucravacitinib group. Also, 62.5% of zasocitinib patients reached PASI 90 compared to 34.0% for deucravacitinib, and a static Physician's Global Assessment (sPGA) score of 0 was recorded in 43.2% versus 18.5% of patients, respectively.

Zasocitinib was shown to be superior in terms of getting those high endpoints, including a PASI 100, PASI 90, vs deucravacitinib at week 16, and we started to see responses early on.

Linda Stein Gold, MD

Zasocitinib Shows High Selectivity for TYK2

Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health in Detroit, Michigan, served as the principal investigator for the LATITUDE Atlas study and explained the distinct biochemical profile of zasocitinib. TYK2 acts as a vital component in the central inflammatory axis for plaque psoriasis. While it belongs to the broader JAK protein family, its primary role centers on regulating immune responses rather than altering lipid metabolism or hematopoiesis.

Zasocitinib demonstrates greater than 1 million-fold selectivity for TYK2 over JAK1, JAK2, or JAK3, maintaining inhibition of interleukin-23 and other key mediators for a full 24 hours. In contrast, deucravacitinib exhibits roughly an 87-fold higher affinity for TYK2 over the other JAKs, with an effect duration lasting about 4.8 hours. The LATITUDE Atlas trial evaluated adults aged 18 and older who had moderate to severe plaque psoriasis for at least 6 months, affecting 10% or more of their body surface area, with a baseline PASI score of 12 or higher and an sPGA of 3 or higher.

Safety Profiles and Long-Term Durability Data

Patient-reported outcomes showed greater reductions in both Dermatology Life Quality Index and itch scores among those receiving zasocitinib. Stein Gold noted that the overall safety and tolerability remained consistent with previous trials, adding that no new safety signals emerged. Treatment-emergent adverse events occurred in nearly 66% of the zasocitinib group and 58.7% of the deucravacitinib group, with most classified as mild or moderate. Discontinuations due to adverse events occurred in 2.6% and 2.3% of patients, respectively.

The most frequent adverse events linked to zasocitinib included nasopharyngitis at 12.9% versus 9.2% for deucravacitinib, upper respiratory tract infection at 11.3% versus 9.2%, dermatitis acneiform at 6.0% versus 1.3%, and acne at 7.3% versus 3.0%. Stein Gold emphasized that the acne cases were mild to moderate, resolved with or without treatment, and did not prompt any patients in the trial to stop therapy.

Additional data presented at the congress from the LATITUDE-PsO-3001 and 3002 trials detailed the drug's long-term profile. April Armstrong, MD, professor and chief of dermatology at the University of California, Los Angeles, reported that over 90% of patients who continued zasocitinib from week 40 through week 60 maintained sPGA 0/1, PASI 75, or PASI 90 responses. More than half of patients maintained those therapeutic responses even after discontinuing the drug entirely. Melinda Gooderham, MD, of Queen’s University and Probity Medical Research in Peterborough, Ontario, presented data regarding the rapidity of onset and quality-of-life impacts.

FDA and EMA Review Zasocitinib for Plaque Psoriasis

Zasocitinib remains an investigational therapy currently undergoing review by the United States Food and Drug Administration and the European Medicines Agency for treating moderate to severe plaque psoriasis. Deucravacitinib has been commercially available in the United States since September 2022 following prior regulatory clearances.