Psoriasis: Selective TYK2 blockade with zasocitinib outperforms apremilast and placebo

Positive results for the treatment of psoriasis with zasocitinib were demonstrated in 2 phase 3 trials. After 16 weeks of treatment with the tyrosine kinase 2 (TYK2) inhibitor, approximately 70% of patients achieved clear or almost clear skin on the static Physician Global Assessment (sPGA).

Zasocitinib is a potent and highly selective oral TYK2 inhibitor, with more than a million-fold greater selectivity for TYK2 over Janus kinase 1 (JAK1) [1]. Dr Melinda Gooderham (SKiN Centre for Dermatology, ON, Canada) presented late-breaking data from the phase 3 LATITUDE-PsO-3001 (NCT06088043) and LATITUDE-PsO-3002 (NCT06108544) trials, which evaluated zasocitinib in patients with moderate-to-severe plaque psoriasis [2]. In addition to the zasocitinib treatment arms, the trials included placebo and an active comparator (apremilast).

Results for the primary endpoint across the 2 trials, comprising a total of 1,801 patients, showed significantly higher rates of sPGA 0/1 with zasocitinib compared with both apremilast and placebo: 71.4% and 69.2% for zasocitinib versus 32.1% and 29.7% for the active comparator, and 10.7% and 12.6% for placebo (P<0.001). Findings for the co-primary endpoint, Psoriasis Area and Severity Index (PASI) 75, were consistent with these results.

PASI 90 responses were achieved by 61.3% and 51.9% of participants receiving zasocitinib compared with 16.8% and 15.9% with apremilast and 5.0% and 4.0% with placebo at week 16. The more stringent secondary endpoint, PASI 100, was reached by 33.4% and 25.2% of patients on zasocitinib versus 2.9% and 4.3% with apremilast and 0.7% and 1.1% with placebo (P<0.001). Treatment responses with zasocitinib continued to improve through week 24.

To assess the durability of response, a withdrawal phase from week 40 to week 60 was included in the trial programme. Patients who achieved PASI 75 at week 40 were re-randomised to either continue zasocitinib or switch to placebo. At week 60, for example, more than 90% of patients who continued TYK2 inhibition in LATITUDE-PsO-3002 maintained their response.

The safety profile of zasocitinib was consistent with previous studies, with no new safety signals identified. The most common adverse events were upper respiratory infections (10.1%), acne (6.5%), and nasopharyngitis (6.2%). Treatment-emergent adverse events through week 16 occurred in 62.1% receiving zasocitinib, compared with 50.5% with apremilast and 46.9% with placebo.

Mehrotra S, et al. J Invest Dermatol. 2026;146(1):214-222.
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). S034 Late-Breaking Research: Session 2. AAD 2026, 27–31 March, Denver, CO, USA.