Zasocitinib Shows Rapid Onset of Action Linked to TYK2 Pathway Modulation in Plaque Psoriasis
A phase 2b study demonstrates that zasocitinib (TAK-279), a highly selective TYK2 inhibitor, produces early clinical responses in moderate-to-severe plaque psoriasis, with improvements closely linked to modulation of key inflammatory pathways and biomarkers.
In this randomized, double-blind, placebo-controlled trial, patients received once-daily zasocitinib (2 mg, 5 mg, 15 mg, or 30 mg) or placebo for 12 weeks. Clinical outcomes were assessed using percent change in Psoriasis Area and Severity Index (PASI), while biomarker analyses included RNA sequencing of skin biopsies and serum proteomics.
Zasocitinib demonstrated rapid clinical efficacy. Reductions in PASI scores were observed as early as week 2, with higher doses achieving greater responses. By week 12, a significantly higher proportion of patients receiving ≥5 mg achieved PASI 75 compared with placebo, and up to 33% of patients receiving 30 mg achieved complete skin clearance (PASI 100).
Importantly, clinical improvements were strongly associated with early biomarker modulation. Changes in IL-23 and type I interferon (IFN) pathway gene expression at week 4 correlated with PASI improvement. Additional analyses showed that both skin gene signatures and circulating serum biomarkers were modulated early and strongly correlated with clinical response at week 12.
“Once-daily oral zasocitinib demonstrated early modulation of TYK2-mediated pathway genes, including IL-23 and type I IFN, and related skin lesion genes and serum biomarkers, which were associated with improved skin clearance at week 4 and week 12,” the authors concluded.
These findings highlight the mechanistic link between TYK2 pathway inhibition and rapid clinical response, supporting zasocitinib as a promising oral therapy for psoriasis.
Reference
Choudhury A, Kumar S, Cheng J, et al. Early onset of response to zasocitinib (TAK-279), a highly selective and potent TYK2 inhibitor, is correlated with modulation of TYK2 signaling and disease pathway biomarkers in patients with moderate-to-severe plaque psoriasis. Presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, Colorado.
