Zasocitinib Shows Early DLQI Gains in Patients with Psoriasis

At the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France, investigators presented new data from a post hoc analysis of a phase 2b trial evaluating zasocitinib (TAK-279; Takeda) in patients with moderate to severe plaque psoriasis.¹ Zasocitinib is an investigational, oral, allosteric tyrosine kinase 2 (TYK2) inhibitor with high selectivity, designed to block IL-23, IL-12, and type I interferon signaling pathways without off-target Janus kinase (JAK) activity. This mechanism offers a distinct therapeutic strategy compared with traditional JAK inhibitors, which are associated with broader immunologic effects and safety concerns.²

Study Overview
The phase 2b study (NCT04999839) was a randomized, multicenter, double-blind, placebo-controlled trial. Patients with moderate to severe plaque psoriasis were randomized 1:1:1:1:1 to receive once-daily zasocitinib at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or placebo, for 12 weeks. The primary endpoint, Psoriasis Area and Severity Index (PASI) 75 at week 12, was met with doses ≥5 mg. In fact, one-third of patients on zasocitinib 30 mg achieved PASI 100.²

The current poster focused on a post hoc analysis of Dermatology Life Quality Index (DLQI) outcomes, a widely used patient-reported outcome assessing quality of life (QoL) across 10 domains. DLQI data were collected at baseline and weeks 4, 8, and 12, and analyzed using mixed models for repeated measures, accounting for treatment, visit, and baseline covariates including prior biologic exposure.

Key Findings

• DLQI Total Score: Patients receiving zasocitinib 30 mg had greater reductions in DLQI total scores versus placebo at weeks 4, 8, and 12, with improvements evident as early as week 4.
• DLQI Domains: At week 12, significant improvements were observed in five of six DLQI domains—Symptoms and Feelings, Daily Activities, Leisure, Work/School, and Personal Relationships. The Treatment domain did not differ significantly between groups, which may reflect the oral formulation’s relatively low treatment burden compared with injectable therapies.
• Individual Questions: Improvements in “Symptoms and Feelings” were particularly notable, including reduced skin discomfort and lower levels of embarrassment and self-consciousness. These improvements were statistically significant as early as week 4.
• DLQI 0/1 Achievement: A greater proportion of patients on zasocitinib achieved DLQI scores of 0 or 1, representing no or minimal impact of psoriasis on quality of life, compared with placebo.

Clinical Interpretation
For clinicians, researchers stated the DLQI findings are noteworthy for several reasons. First, improvements in patient-reported outcomes occurred in parallel with PASI responses, reinforcing that zasocitinib can address both clinical and psychosocial disease burden. Second, the rapid onset of QoL benefits may be particularly meaningful in patient populations where symptoms such as itch, pain, and stigma drive health care seeking behavior. Third, the oral, once-daily dosing could make zasocitinib a more practical option for patients hesitant about injectable biologics, potentially improving adherence and satisfaction.

The TYK2-selective mechanism is another clinically relevant feature. Unlike pan-JAK inhibition, which carries boxed warnings for serious infections, malignancy, and cardiovascular events, researchers noted zasocitinib’s high selectivity may mitigate some of these safety concerns. However, long-term data remain essential, as the phase 2b study was limited to 12 weeks. Two ongoing phase 3 trials (NCT06088043 and NCT06108544) will provide critical data on durability, safety, and real-world applicability.

Conclusion
Data presented at EADV 2025 in Paris demonstrate that zasocitinib, an oral TYK2 inhibitor, improved DLQI total scores, individual domains, and achievement of DLQI 0/1 in patients with moderate to severe plaque psoriasis. Improvements were observed as early as week 4 and were sustained through week 12. These findings suggest that zasocitinib may offer meaningful quality of life benefits alongside robust PASI responses. Pending confirmation in phase 3 studies, zasocitinib could represent an important addition to the therapeutic landscape, especially for patients seeking an oral alternative to biologics.

References

1. Bhutani T, Spector T, Winkelman W, et al. Treatment with zasocitinib (TAK 279), an investigational, oral, allosteric, highly selective and potent tyrosine kinase 2 inhibitor, is associated with improvements in Dermatology Life Quality Index in patients with moderate-to-severe plaque psoriasis. Poster presented at: EADV 2025; September 17-20; Paris, France.
2. Armstrong AW, Gooderham M, Lynde C, et al. Tyrosine kinase 2 inhibition with zasocitinib (TAK-279) in psoriasis: a randomized clinical trial. JAMA Dermatol. 2024;160(10):1066-1074. doi:10.1001/jamadermatol.2024.2701