TYK2-inhibition in PsA: zasocitinib shows benefits in minimal disease activity and PASI

Phase 2b results for zasocitinib in psoriatic arthritis (PsA) showed promising efficacy in achieving minimal disease activity (MDA) and Psoriasis Area Severity Index (PASI) responses. At the 30 mg dose, 29.2% of participants reached MDA, and 45.7% achieved PASI75.

In the phase 2b trial (NCT05153148), participants with active PsA received the selective, allosteric tyrosine kinase 2 (TYK2) inhibitor zasocitinib at doses of 5 mg, 15 mg, or 30 mg daily. The study met its primary endpoint of ACR20 response versus placebo (53.3% with 15 mg, 54.2% with 30 mg, 29.2% with placebo; P=0.002) at week 12. Dr Alan Kivitz (Altoona Arthritis and Osteoporosis Center in Duncansville, PA, USA) now presented insights on secondary and post hoc endpoints [1].

The study included 290 adult participants meeting the CASPAR criteria for PSA with symptoms for at least 6 months before screening. The mean age was 49.9 years, 57.2% were women, and the mean BMI was 29.9 kg/m². Nearly one-third of participants had previous treatment with biologics, including around 20% with prior anti-TNF.

At week 12, MDA was achieved in significantly more participants in the 15 and 30 mg groups compared with placebo (28.0% and 29.2% vs 12.5%, respectively; P<0.05 for both). MDA in the 5 mg arm was 18.3%, which did not reach statistical significance.

PASI responses were significant in the 30 mg arm, with 45.7% of participants achieving PASI75 and 37.0% PASI90, compared to 15.4% and 10.3% in placebo, respectively (P<0.01). Furthermore, zasocitinib 30 mg outperformed the placebo group in achieving total or near-total clearance of psoriasis lesions (P=0.034).

Zasocitinib was well tolerated, with nasopharyngitis and headache being the most common adverse events. Serious treatment-emergent adverse events were observed in 5.6% on placebo and 2.8–5.6% on zasocitinib.

The authors concluded that this study's efficacy and safety findings support the continued clinical development of zasocitinib in PsA.

 

1. Gottlieb AB, et al. Zasocitinib (TAK-279), a highly selective oral tyrosine kinase 2 (TYK2) inhibitor, elicits minimal disease activity and early skin responses in patients with active psoriatic arthritis: results from a randomised phase 2b study. POS0107, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 18 June 2025