Zasocitinib Bests Deucravacitinib on PsO Skin Clearance in Phase 3 Head-to-Head

Zasocitinib, an investigational once-daily oral tyrosine kinase 2 (TYK2) inhibitor, achieved statistically superior rates of complete skin clearance compared with deucravacitinib across all primary and key secondary endpoints in a Phase 3 head-to-head trial in adults with moderate-to-severe plaque psoriasis (PsO), according to topline results announced today by Takeda.¹

In the LATITUDE Atlas study (NCT06973291), more than 35% of patients receiving zasocitinib 30 mg once daily reached a Psoriasis Area and Severity Index (PASI) 100 response — indicating total skin clearance — at week 16, the primary endpoint. That rate was more than 2.5 times higher than the PASI 100 response seen in patients receiving deucravacitinib 6 mg once daily. The press release did not disclose the absolute PASI 100 rate for the deucravacitinib arm or statistical values for individual endpoints; full data are expected to be presented at upcoming medical congresses.¹

Superiority over deucravacitinib was also demonstrated for all key secondary endpoints, including PASI 90 response and Static Physician's Global Assessment (sPGA) 0 at week 16. Separation between treatment arms was observed as early as week 8, according to Takeda.¹

"In this head-to-head study, zasocitinib clearly demonstrated superior skin clearance compared with deucravacitinib, highlighting clinically meaningful differences within the oral treatment class," said Linda Stein Gold, MD, Director of Dermatology Clinical Research at Henry Ford Health and principal investigator for the LATITUDE Atlas study.¹ "As expectations for oral therapies continue to rise, these findings support the potential of zasocitinib to help transform what patients and physicians can expect from an oral option in plaque psoriasis."

The double-blind, randomized trial enrolled 606 participants across multiple centers. Patients were randomized to zasocitinib 30 mg or deucravacitinib 6 mg once daily through 16 weeks, with a 4-week safety follow-up period. No new safety signals were identified, and the tolerability profile was consistent with earlier zasocitinib studies.¹

These head-to-head results extend a body of Phase 3 data on zasocitinib building since late 2025. In the pivotal LATITUDE PsO 3001 and 3002 studies — presented as a late-breaking abstract at the 2026 American Academy of Dermatology (AAD) Annual Meeting — approximately 70% of zasocitinib-treated patients achieved clear or almost clear skin (sPGA 0/1) at week 16, with a significantly greater PASI 75 response versus placebo emerging as early as week 4.² Among patients achieving PASI 75, PASI 90, or sPGA 0/1 at week 40, more than 90% maintained responses through week 60, suggesting durable benefit with continued treatment.²

Zasocitinib is designed to inhibit TYK2 with more than 1-million-fold selectivity over JAK1, 2, and 3 based on in vitro data — an allosteric binding mechanism intended to block the IL-23/IL-17 axis and type I interferon signaling that drive psoriatic inflammation while avoiding the broader JAK-family off-target effects associated with cardiovascular and hematologic risk.¹ Deucravacitinib (Sotyktu; Bristol Myers Squibb), approved by the FDA in 2022, uses a distinct allosteric TYK2 inhibition mechanism and is currently the only approved oral TYK2 inhibitor for plaque psoriasis.³

Takeda is on track to submit a New Drug Application to the FDA for plaque psoriasis during the current fiscal year. The company is also evaluating zasocitinib in Phase 3 studies in psoriatic arthritis and Phase 2 studies in Crohn's disease, ulcerative colitis, vitiligo, and hidradenitis suppurativa. Zasocitinib has not been approved by any regulatory authority.¹

References

1. Takeda Pharmaceutical Company Limited. Takeda's zasocitinib significantly outperforms deucravacitinib in head-to-head Phase 3 psoriasis study, promising to redefine oral treatment expectations. Press release. June 11, 2026. https://www.takeda.com/newsroom/newsreleases/2026/zasocitinib-outperforms-deucravacitinib-study/

2. Gooderham M, et al. Once-daily oral zasocitinib demonstrates rapid and reproducible skin clearance with a consistent safety profile in moderate-to-severe plaque psoriasis: results from two randomized Phase 3 trials (LATITUDE-PsO-3001 and 3002). Late-breaking abstract presented at: American Academy of Dermatology Annual Meeting; March 28, 2026; Denver, CO.

3. 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