FDA Accepts Takeda's Zasocitinib NDA Under Priority Review for Moderate-to-Severe Plaque Psoriasis
核心洞察
The FDA accepted Takeda's New Drug Application under Priority Review for zasocitinib (TAK-279) in adults with moderate-to-severe plaque psoriasis (搜索), with a PDUFA date in the first quarter of 2027.
The filing rests on pivotal Phase 3 LATITUDE PsO 3001 and 3002 trials in which all co-primary and 44 ranked secondary endpoints were met across nearly 3,000 patients.
At week 16, roughly 70% of zasocitinib-treated patients achieved sPGA 0/1 versus 11-13% on placebo and 30-32% on apremilast, with PASI 75 rates of 71-76% versus 12% and 33-37%.
Takeda announced that the U.S. Food and Drug Administration (搜索) has accepted its New Drug Application under Priority Review for zasocitinib (TAK-279) for the treatment of adults with moderate-to-severe plaque psoriasis (搜索). The Prescription Drug User Fee Act target action date falls in the first quarter of calendar year 2027, and the company said the filing has no significant impact on its full-year consolidated financial forecast for the fiscal year ending March 31, 2027.
Zasocitinib is an investigational, next-generation, highly selective and potent oral tyrosine kinase 2 (TYK2 (搜索)) inhibitor that the company says maintains 24-hour inhibition of IL-23 (搜索) plus other core disease-driving immune pathways. If approved, it would be administered as a once-daily pill. Zasocitinib has not been approved for use by any regulatory authority.
Pivotal Phase 3 Data Package
The NDA is supported by the pivotal global Phase 3 LATITUDE PsO 3001 (NCT06088043) and 3002 (NCT06108544) studies, in which the co-primary and all 44 ranked secondary endpoints were met, according to Takeda. Both are global, multicenter, randomized, double-blind, placebo- and active comparator-controlled studies evaluating efficacy, safety and tolerability in adult patients with moderate-to-severe plaque psoriasis (搜索). The trials were conducted in 21 countries, with LATITUDE PsO 3001 enrolling 693 participants and LATITUDE PsO 3002 enrolling 1,108 participants.
The co-primary endpoints were the proportion of zasocitinib-treated patients achieving static Physician Global Assessment (sPGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75 response compared with placebo at week 16. Ranked secondary endpoints included comparisons versus placebo at week 16 and versus apremilast at week 16 and week 24.
At week 16, sPGA 0/1 was achieved by 71% of zasocitinib-treated patients versus 11% on placebo and 32% on apremilast in LATITUDE PsO 3001, and by 69% versus 13% and 30%, respectively, in LATITUDE PsO 3002 (p<0.001 for both studies). PASI 75 responses were 76% versus 12% and 37% in 3001, and 71% versus 12% and 33% in 3002 (p<0.001).
Deeper clearance measures also favored zasocitinib. PASI 90 was achieved by 61% versus 5% on placebo and 17% on apremilast in 3001, and 52% versus 4% and 16% in 3002 (p<0.001). Complete clearance, measured as sPGA 0, was reached by 40% versus 0.7% and 8% in 3001, and 34% versus 1% and 7% in 3002, while PASI 100 was achieved by 33% versus 0.7% and 3% in 3001, and 25% versus 1% and 4% in 3002 (p<0.001 for all).
Clearance at High-Impact Sites
The program also assessed involvement of hard-to-treat and high-impact anatomical sites. Scalp-specific PGA 0/1 at week 16 was achieved by 77% of zasocitinib-treated patients versus 7% on placebo and 42% on apremilast in LATITUDE PsO 3001, and by 74% versus 13% and 30% in LATITUDE PsO 3002 (p<0.001). Least-squares mean change from baseline in the Nail Psoriasis Severity Index was -7.1 with zasocitinib versus 1.8 with placebo in 3001 and -8.6 versus -1.4 in 3002 (p<0.001).
Palmoplantar PGA 0/1 responses were 71% with zasocitinib versus 22% on placebo and 44% on apremilast in 3001, and 69% versus 10% and 43% in 3002. Takeda noted that palmoplantar PGA was not a multiplicity-controlled secondary endpoint and that comparisons with apremilast are descriptive and should be interpreted accordingly. In LATITUDE PsO 3002, 17% of zasocitinib-treated patients achieved PASI 75 by week 4 versus 4% on placebo (p<0.001).
"Despite progress in psoriasis care, there remains a need for highly effective oral therapies that also address the diverse and often challenging manifestations of psoriasis, including involvement of high-impact sites like the scalp," said Andy Plump, M.D., Ph.D., president of R&D at Takeda. "Our Phase 3 data demonstrated rapid and durable skin clearance across various patient types and in high-impact and hard-to-treat areas. Based on the results across nearly 3,000 patients, zasocitinib has the potential to be a leading oral treatment option in psoriasis."
Safety and Long-Term Data
Across the two studies, the most common adverse events occurring in at least 5% of patients were upper respiratory tract infection (10.1%), nasopharyngitis (6.2%) and acne (6.5%), based on sample size adjusted incidence proportions across the two studies. No new safety signals were identified, and the safety profile was consistent with previous studies.
Supportive data came from LATITUDE PsO 3003 (NCT06550076), a Phase 3, multicenter, open-label study evaluating long-term safety, tolerability and efficacy. The study enrolled approximately 2,100 participants in two parts: in Part A, patients not previously exposed to zasocitinib received 30 mg once daily for up to 52 weeks, while patients completing Part A or the treatment period in LATITUDE PsO 3001 and 3002 received zasocitinib for up to 156 weeks in Part B. The primary endpoint was the number of zasocitinib-treated patients with treatment-emergent and serious adverse events; secondary endpoints were the proportions achieving sPGA 0/1 and PASI 75.
Mechanism and Broader Development
TYK2 (搜索) is described as a central mediator of core inflammatory pathways in psoriasis — the IL-23 (搜索)/IL-17 axis and type I interferon signaling — and is an intracellular enzyme within the Janus kinase (JAK) protein family. Unlike JAK1 (搜索), 2 and 3, which regulate broader biological processes such as lipid metabolism and hematopoiesis, TYK2 primarily regulates immune responses. According to in vitro data, zasocitinib has more than 1-million-fold greater selectivity for TYK2 compared with other JAK enzymes, which the company says could maximize TYK2 inhibition without impacting JAK1, 2 and 3 signaling.
Beyond plaque psoriasis, Takeda is evaluating zasocitinib in Phase 3 studies in psoriatic arthritis (搜索) and in Phase 2 studies in Crohn's disease (搜索), ulcerative colitis (搜索), vitiligo (搜索) and hidradenitis suppurativa (搜索).
Regulatory Outlook
The European Medicines Agency (搜索) has also accepted Takeda's new marketing authorization application for zasocitinib, initiating the review process for moderate-to-severe plaque psoriasis (搜索). Takeda said it plans to submit additional applications for plaque psoriasis with global regulatory authorities.
Psoriasis is a chronic, systemic immune-mediated inflammatory disease characterized by itchy, painful, disfiguring and disabling skin lesions that affect physical, emotional and psychological wellbeing. Globally, an estimated 66.4 million people are living with psoriasis, and about 80-90% of those have plaque psoriasis. Persistent itch, the appearance and location of lesions — particularly at highly visible or high-impact sites — and related comorbidities such as psoriatic arthritis (搜索) play a major role in reducing quality of life.