Zasocitinib Data Demonstrates Efficacy of TYK2 Inhibition for Psoriatic Arthritis

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) with a manageable safety profile, in new findings from a phase 2b study.1

“Despite current treatment options, some patients with PsA continue to experience a high disease burden because available treatments may not adequately address all core PsA domains, while also not providing acceptable long-term safety.2 This highlights the need for more comprehensive treatment strategies in patients without adequate disease control or with tolerability issues with current treatments and ultimately improvement in the long-term outcomes and quality of life of these patients with PsA,” lead investigator Alan Kivitz, MD, president and founder, Altoona Center for Clinical Research, Duncansville, Pennsylvania, and colleagues wrote.1

The new data are from a randomized, multicenter, double-blind, placebo-controlled, multiple-dose study that included adults with PsA receiving 30 mg, 15 mg, or 5 mg zasocitinib or placebo (1:1:1:1) once daily for 12 weeks, with a 4-week safety follow-up. The study primarily assessed ACR20 response at week 12, with secondary efficacy endpoints including ACR50 response, ACR70 response, Psoriasis Area and Severity Index (PASI) 75 response among those with ≥3% body surface area at baseline and MDA at week 12.

“We all know that TYK2s, the whole claim to fame is that you're kind of 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 il 12, il 23, th 17 and the like we 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,” investigator Andrew Sharobeem, DO, a rheumatologist at Arizona Arthritis & Rheumatology Associates, told HCPLive.

Overall, the study included 290 patients with a mean age of 49.9 years (standard deviation [SD], 11.6), 57.1% of which were female. Kivitz 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%). A similar but non-significant trend was seen with ACR50 responses 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%). Furthermore, participants that received 30 mg zasocitinib had a numerically higher number of ACR70 responses (13.9% versus 5.6% in placebo; nominal P = .158), PASI 75 responses (45.7% versus 15.4%, respectively; nominal P = .002), and MDA (29.2% versus 12.5%, respectively; nominal P = .014) at week 12 than those who received placebo.

Most adverse events (AEs) were mild or moderate and occurred 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 due to TEAEs ranged from 8.5% to 12.5% across zasocitinib doses versus 5.6% with placebo and was mostly due to TEAEs determined to be unrelated to study treatment. No new safety signals or dose-dependent lab abnormalities were observed.

“The lack of safety events associated with JAK1, JAK2, or JAK3 inhibition is reflective of the highly selective TYK2 inhibition of zasocitinib. These results highlight the potential of zasocitinib as a new oral therapeutic option in patients with active PsA. Consequently, phase 3 studies are ongoing (NCT06671483 and NCT06671496) to explore its full potential and to confirm these preliminary results in larger, more diverse patient populations, aiming to improve management and outcomes for patients with PsA,” Kivitz and colleagues concluded.1

REFERENCES

1. 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

2. Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis. Published online March 18, 2024:ard-225531. doi:https://doi.org/10.1136/ard-2024-225531