Once-Daily Zasocitinib Rivals Injectable Biologics for Skin Clearance, Phase 3 Data Show

Complete skin clearance from a once-daily pill—achieved in more than one-third of patients. That was the headline finding from LATITUDE Atlas, a phase 3, randomized, double-blind trial in which zasocitinib (TAK-279; Takeda) demonstrated statistical superiority over deucravacitinib (Sotyktu; Bristol-Myers Squibb) across all primary and key secondary endpoints in adults with moderate to severe plaque psoriasis, reinforcing the case that next-generation TYK2 inhibitors are rewriting expectations for oral therapy.¹

In the LATITUDE Atlas trial (NCT06973291), 606 participants were randomized to zasocitinib 30 mg once daily or deucravacitinib 6 mg once daily for 16 weeks. The primary endpoint—PASI 100 response rate at week 16—was met with statistical significance in favor of zasocitinib. More than 35% of zasocitinib-treated patients achieved complete skin clearance at that timepoint, compared with approximately 14% in the deucravacitinib arm, a more than 2.5-fold difference. Separation between treatment curves emerged as early as week 8.

Key secondary endpoints—PASI 90 response and static Physician’s Global Assessment (sPGA) of 0 at week 16—also favored zasocitinib with statistical significance. The safety and tolerability profile was consistent with prior phase 3 data, with no new safety signals identified.

“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. “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.”

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Phase 3 Program Results

The LATITUDE Atlas data build on results from the broader LATITUDE phase 3 program (NCT06088043, NCT06108544), which evaluated zasocitinib against both placebo and the active comparator apremilast. Co-primary endpoints included sPGA 0/1 and PASI 75 at week 16.²

Across those trials, approximately 70% of patients achieved clear or nearly clear skin (sPGA 0/1) at week 16, with PASI 90 responses exceeding 50% and reaching over 60% in some cohorts. Up to 49% of patients achieved sPGA 0 and 42% reached PASI 100—stringent endpoints historically associated with biologic therapy. At week 24, two-thirds of patients reached PASI 90 and roughly one-third achieved PASI 100. Durability data extended to week 60 showed over 90% of patients maintaining clear or nearly clear skin, addressing longstanding questions about oral agent durability.

Rapid onset was a consistent feature: separation from placebo was observed as early as week 4. Quality-of-life gains were also notable—by week 24, up to 60% of patients achieved Dermatology Life Quality Index (DLQI) scores of 0 or 1, indicating no meaningful impact of psoriasis on daily life.

“Our goal in psoriasis treatment is clear or almost clear skin, and previously this has been achieved primarily with injectable therapies,” said Melinda Gooderham, MD, commenting on the LATITUDE data. “These findings show it’s possible for a once-daily pill to deliver rapid, lasting skin clearance.”

A Competitive Next-Generation Class

Zasocitinib is not alone in pushing the efficacy ceiling for oral psoriasis therapy. Envudeucitinib (ESK-001; Alumis), another next-generation TYK2 inhibitor, reported similarly striking phase 3 results from the ONWARD trials (NCT04729907). Approximately 75% of patients achieved PASI 75 by week 16, rising to roughly 80% by week 24, with 40% reaching PASI 100 at week 24—comparable figures to zasocitinib’s LATITUDE outcomes.

Both agents share a design philosophy centered on near-complete 24-hour TYK2 inhibition while sparing JAK1, JAK2, and JAK3. Envudeucitinib demonstrated no lipid elevations, a concern historically associated with broader JAK inhibition. Zasocitinib achieves more than 1-million-fold selectivity for TYK2 over other JAK family members based on in vitro data. Across both programs, safety profiles were consistent with the TYK2 class: no new signals, no tuberculosis reactivation, and no cardiovascular events; adverse events were predominantly mild upper respiratory and infectious processes.

A notable finding across both programs was the temporal dissociation between symptomatic relief and visible skin clearance. In the ONWARD trials, patients reported meaningful reductions in pruritus by week 2 and quality-of-life gains by week 12—before peak skin clearance was achieved. “The DLQI actually significantly starts to improve at week 2, prior to any real significant changes in skin,” noted Andrew Blauvelt, MD, MBA, an investigator in the ONWARD trials, in a recent interview with Dermatology Times. “So the DLQI seems to be paralleling the itch response in that first month of treatment.” Zasocitinib showed a similar early-onset pattern, with placebo separation at week 4.

Mechanism and Selectivity

TYK2 is a central mediator of the IL-23/IL-17 axis and type I interferon signaling—pathways that drive psoriasis pathogenesis. Unlike JAK1, JAK2, and JAK3, which regulate broader biological processes including lipid metabolism and hematopoiesis, TYK2 primarily mediates immune responses. Allosteric inhibition of TYK2 with high JAK selectivity is intended to maximize anti-inflammatory efficacy while potentially limiting the cardiovascular and hematologic risks associated with pan-JAK inhibition.

Deucravacitinib, the first approved allosteric TYK2 inhibitor, remains the only oral TYK2 agent on the market for moderate to severe plaque psoriasis. The LATITUDE Atlas data position zasocitinib as a potentially superior entrant within that same mechanistic class.

Regulatory Status and Broader Program

Takeda is on track to submit a New Drug Application (NDA) for plaque psoriasis to the US FDA and other regulatory authorities within the current fiscal year. Detailed data from LATITUDE Atlas are expected to be presented at upcoming medical congresses, building on the LATITUDE-PsO results presented at the AAD 2026 Annual Meeting.²

Beyond plaque psoriasis, Takeda is evaluating zasocitinib in phase 3 studies in psoriatic arthritis and phase 2 studies in Crohn’s disease, ulcerative colitis, vitiligo, and hidradenitis suppurativa. The compound has not yet been approved for use by any regulatory authority.

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References

1. Takeda’s zasocitinib significantly outperforms deucravacitinib in head-to-head phase 3 psoriasis study, promising to redefine oral treatment expectations. News release. Takada. Published June 11, 2026. Accessed June 11, 2026. https://www.takeda.com/newsroom/newsreleases/2026/zasocitinib-outperforms-deucravacitinib-study/
2. Takeda’s zasocitinib delivered rapid and durable skin clearance in a convenient once-daily pill, affirming promise to reshape psoriasis care. Late-breaking abstract presented at: AAD 2026; March 27-31, 2026; Denver, CO.