Zasocitinib Demonstrates Superiority vs Placebo and Apremilast in Phase 3 Plaque Psoriasis Trials

Takeda announced positive topline results from 2 pivotal phase 3 trials showing that once-daily oral zasocitinib met all primary and ranked secondary endpoints in adults with moderate-to-severe plaque psoriasis, demonstrating superiority over placebo and the active comparator apremilast at week 16.

According to the company, the randomized, multicenter, double-blind studies showed significantly higher response rates with zasocitinib compared with placebo for the coprimary endpoints of static Physician Global Assessment (sPGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75 at week 16. A significantly greater PASI 75 response was observed as early as week 4 and continued to increase through week 24.

All 44 ranked secondary endpoints were met, including PASI 90, PASI 100, and sPGA 0 versus placebo and apremilast. More than half of participants treated with zasocitinib achieved clear or almost clear skin, defined as PASI 90, and on average about 30% achieved completely clear skin, defined as PASI 100, by 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," Andy Plump, MD, PhD, president of R&D at Takeda, said in a press release.

Zasocitinib was generally well tolerated, with a safety and tolerability profile consistent with prior clinical studies, including a phase 2b plaque psoriasis trial. The most common adverse events reported through week 24 were upper respiratory tract infection, nasopharyngitis, and acne. Takeda reported no new safety signals identified in the phase 3 program.

Takeda plans to present the phase 3 data at upcoming medical congresses and intends to submit a New Drug Application to the US Food and Drug Administration and other regulatory authorities beginning in fiscal year 2026. The company noted that the results do not have a significant impact on its full-year consolidated forecast for the fiscal year ending March 31, 2026.

In addition to plaque psoriasis, zasocitinib is being evaluated in a head-to-head phase 3 study against deucravacitinib in plaque psoriasis, phase 3 studies in psoriatic arthritis, and phase 2 studies in Crohn disease and ulcerative colitis. Additional phase 2 studies are ongoing or being initiated in other immune-mediated inflammatory diseases.

Zasocitinib (TAK-279) is an investigational, next-generation, highly selective oral tyrosine kinase 2 inhibitor designed to maintain 24-hour inhibition of interleukin-23 and other immune pathways involved in psoriasis. Based on in vitro data, the compound demonstrates more than 1-million-fold greater selectivity for TYK2 compared with other Janus kinase enzymes. Zasocitinib has not been approved for use by any regulatory authority.

The phase 3 LATITUDE psoriasis program consisted of 2 global studies conducted across 21 countries, enrolling 693 and 1108 adults with moderate-to-severe plaque psoriasis. The coprimary endpoints were the proportion of participants achieving sPGA 0/1 and PASI 75 compared with placebo at week 16, with ranked secondary endpoints evaluating efficacy compared to placebo and apremilast at weeks 16 and 24.

Reference: 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. Takeda. December 18, 2025. Accessed December 18, 2025. https://www.takeda.com/newsroom/newsreleases/2025/takeda-zasocitinib-phase-3-plaque-psoriasis-data-once-daily-pill/