Phase 3 Data Position Zasocitinib as a Potential New Oral Option for Psoriasis

The therapeutic landscape for moderate to severe plaque psoriasis continues to evolve rapidly, particularly in the oral systemic space, where clinicians and patients alike seek options that balance efficacy, safety, and convenience. Takeda’s recent announcement of positive topline results from 2 pivotal phase 3 trials of zasocitinib (TAK-279), an investigational oral tyrosine kinase 2 (TYK2) inhibitor, adds important new data to this discussion.¹

The 2 studies were randomized, multicenter, double-blind, and controlled against both placebo and an active comparator (apremilast), enrolling adults with moderate to severe plaque psoriasis. Both trials met their co-primary endpoints: achievement of static Physician Global Assessment (sPGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75 at week 16. Notably, superiority versus placebo was observed, with PASI 75 responses emerging as early as week 4 and continuing to increase through week 24.

“2025 is ending and 2026 is starting with a major bang in dermatology. The long awaited phase 3 clinical trial results from the next generation Tyk2 inhibitor zasocitnib is here. The results delivered in a big way. This oral daily therapy achieved PASI-90 in over 50% of patients by week 16, and PASI-100 in around 30% of patients by week 16," said Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine in New Haven, Connecticut, and Dermatology Times Editor in Chief, in an exclusive statement. "This positions zasocitinib to potentially be the best oral therapy in plaque psoriasis. Demonstrating superiority over apremilast, and meeting all primary and 44 secondary ranked endpoints is impressive. I couldn't be happier for patients suffering from psoriasis, as they now have on the horizon a game-changing effective and safe oral therapy. I look forward to learning more details on zasocitinib’s phase 3 trials that will be shared at upcoming congresses in 2026.”

Beyond the primary outcomes, all 44 ranked secondary endpoints were reportedly met. These included higher thresholds of skin clearance—PASI 90, PASI 100, and sPGA 0—compared with both placebo and apremilast. From a clinical standpoint, such endpoints are increasingly relevant, as treatment goals in psoriasis have shifted from partial improvement toward near-complete or complete clearance for many patients.

Takeda highlighted that more than half of patients treated with zasocitinib achieved PASI 90 at week 16, while approximately 30% reached PASI 100, with continued improvement through week 24. Andy Plump, MD, PhD, president of R&D at Takeda, commented in a news release:

“It is incredibly rewarding and exciting to see our phase 2 results validated in phase 3, with more than half of patients treated with zasocitinib achieving clear or almost clear skin (PASI 90) and about 30 percent achieving completely clear skin (PASI 100) at week 16, with response rates continuing to increase through week 24. These findings help demonstrate that highly selective inhibition of TYK2, a key mediator of IL-23 and other signaling pathways fundamental to psoriasis, may provide patients with significant reductions in their disease burden, including for many, the possibility of complete skin clearance.”

Zasocitinib is designed to selectively inhibit TYK2, a key intracellular mediator of IL-23 and other cytokine pathways implicated in psoriasis pathogenesis. According to Takeda, the compound demonstrates more than one-million-fold selectivity for TYK2 over JAK1, JAK2, and JAK3 based on in vitro data. This selectivity is intended to preserve efficacy while minimizing off-target effects associated with broader JAK inhibition, an issue that has shaped regulatory and clinical caution around JAK inhibitors in inflammatory diseases.²

Safety outcomes through week 24 were described as generally favorable and consistent with earlier studies, including a phase 2b trial. The most common adverse events were upper respiratory tract infection, nasopharyngitis, and acne, with no new safety signals identified.

From a patient-centered perspective, the appeal of an effective once-daily oral therapy is clear. Christophe Weber, Takeda’s president and CEO, noted, “People living with psoriasis continue to seek safe, effective and fast-acting oral therapies. These landmark results support zasocitinib’s promise to become a leading oral treatment option that can deliver clear skin for patients with plaque psoriasis.” However, translating trial efficacy into real-world effectiveness will depend on durability of response, adherence, tolerability, and access considerations.

Several important questions remain unanswered at this stage. Detailed trial design elements, such as dosing strategies, baseline disease characteristics, prior biologic exposure, and subgroup analyses, have not yet been publicly disclosed. Additionally, while apremilast serves as a reasonable oral comparator, many clinicians will be particularly interested in head-to-head data versus other TYK2 inhibitors, including deucravacitinib, especially given differences in molecular selectivity and emerging long-term safety profiles.

Takeda has indicated plans to present the full data at upcoming medical congresses and to begin regulatory submissions in fiscal year 2026. Zasocitinib is also being evaluated in psoriatic arthritis, inflammatory bowel disease, vitiligo, and hidradenitis suppurativa, suggesting a broader strategy targeting immune-mediated inflammatory diseases.

The phase 3 results for zasocitinib suggest that selective TYK2 inhibition may offer a potent oral option for patients with moderate to severe plaque psoriasis, achieving high levels of skin clearance with an apparently manageable safety profile. For clinicians, these findings are encouraging but preliminary; thoughtful integration into practice will depend on full data transparency, longer-term outcomes, and comparative effectiveness within an increasingly crowded therapeutic field.

References

1. Takeda’s zasocitinib landmark phase 3 plaque psoriasis data show promise to deliver clear skin in a once-daily pill, catalyzing a new era of treatment. News release. Takada. Published December 18, 2025. Accessed December 18, 2025. https://www.takeda.com/newsroom/newsreleases/2025/takeda-zasocitinib-phase-3-plaque-psoriasis-data-once-daily-pill/
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