TYK2 Inhibitor Zasocitinib’s Potential for Psoriatic Arthritis, with Andrew Sharobeem, DO

New findings from a phase 2b study have shown that zasocitinib 30 mg and 15 mg demonstrated efficacy across American College of Rheumatology (ACR) and minimal disease activity (MDA) responses in people with active psoriatic arthritis (PsA) and had a manageable safety profile.

HCPLive spoke with primary investigator Andrew Sharobeem, DO, Arizona Arthritis & Rheumatology Associates, to learn more about zasocitinib and its potential in offering a new treatment for people with PsA.

The randomized, multicenter, double-blind, placebo-controlled, multiple-dose study included 290 patients with a mean age of 49.9 years (standard deviation [SD], 11.6), 57.1% of which were female. Sharobeem and colleagues found that at week 12, participants that received 30 mg (54.2%; P = .002) or 15 mg (53.3%; P = .002) zasocitinib treatment had significantly higher rates of ACR20 responses than placebo (29.2%). Similarly, higher rates of ACR50 responses were achieved at week 12 with 30 mg (26.4%; nominal P = .009) or 15 mg (26.7%; nominal P = .005) zasocitinib over placebo (9.7%), although this was a non-significant trend.

Zasocitinib was well-tolerated in study participants, with most adverse events (AEs) being mild or moderate and occurring more frequently in the higher dose zasocitinib groups (TEAEs: 77.8% at 30 mg vs 54.2% with placebo). Grade 3 AEs were reported in 7.6% of participants overall, with only one Grade 4 event (unrelated to treatment). Discontinuation rates due to TEAEs were similar between zasocitinib (8.5% and 12.5%) and placebo groups (5.6%) and was mostly due to TEAEs determined to be unrelated to study treatment.

“We all know that TYK2s, the whole claim to fame is that you're avoiding that whole JAK1, JAK2 situation, so you don't have to worry about blocking anything. You don't need to block downstream. And so, we're excited about the cleaner safety profiles going down that whole IL12, IL23, TH17 and the like. We appreciate what it is and what it offers and what it doesn't do, if you will. So, we're excited to see more and more come out as the trial proceeds, and so far, so good,” Sharobeem said.

Sharobeem has no relevant disclosures to report.

REFERENCE

Kivitz A, Baraliakos X, Muensterman ET, et al. Highly selective tyrosine kinase 2 inhibition with zasocitinib (TAK-279) improves outcomes in patients with active psoriatic arthritis: a randomized phase 2b study. Ann Rheum Dis. Published online July 2025. doi: 10.1016/j.ard.2025.05.023