Takeda's zasocitinib aces Phase III in moderate-to-severe plaque psoriasis trials

Takeda (TSE:4502/NYSE:TAK) reported that zasocitinib, its investigational oral TYK2 inhibitor, met co-primary endpoints in two Phase III trials in adults with moderate-to-severe plaque psoriasis, with approximately 70% of patients achieving clear or almost clear skin at week 16 — a response rate that places the once-daily pill well above the oral active comparator used in both studies.

Trial specifics

The Latitude PsO 3001 and Latitude PsO 3002 studies are global, randomized, double-blind, placebo- and active comparator-controlled Phase III trials enrolling 693 and 1,108 adults, respectively, with moderate-to-severe plaque psoriasis across 21 countries.

Across both studies, 71.4% and 69.2% of zasocitinib-treated patients achieved a static Physician Global Assessment (sPGA) score of 0/1 at week 16, compared with 10.7% and 12.6% for placebo and 32.1% and 29.7% for apremilast (all p<0.001). PASI 90 rates of 61.3% and 51.9% were observed with zasocitinib versus approximately 16% for apremilast at the same timepoint. In Latitude PsO 3002, a statistically significant PASI 75 separation from placebo was detectable as early as week 4 (16.8% vs 4.3%, p<0.001), and among patients who maintained response through week 40, over 90% retained their response at week 60.

Treatment-emergent adverse events through week 16 were more frequent with zasocitinib (62.1%) than with placebo (46.9%) or apremilast (50.5%), with serious TEAEs in 3.0% of zasocitinib patients versus less than 1% for placebo. The most common events were upper respiratory tract infection (10.1%), acne (6.5%), and nasopharyngitis (6.2%), with no new safety signals identified relative to Phase IIb data.

Zasocitinib lining up BMS's Sotyktu

Zasocitinib allosterically inhibits TYK2 by binding the pseudokinase (JH2) domain, suppressing downstream IL-23 and related cytokine signaling implicated in psoriasis pathogenesis. Takeda claims more than one-million-fold selectivity for TYK2 over JAK1, JAK2, and JAK3 based on in vitro data — a selectivity profile it is positioning as a differentiator from Bristol Myers Squibb's deucravacitinib (Sotyktu), the only currently approved TYK2 inhibitor in plaque psoriasis.

Deucravacitinib shares the same allosteric JH2 binding mechanism and is the closest mechanistic comparator, and Takeda is carrying out a head-to-head trial between the two agents. Cross-trial comparisons are limited by differences in patient populations, study designs, and endpoints, but the week-16 sPGA 0/1 rates for zasocitinib appear numerically higher than those reported in deucravacitinib's pivotal Phase III program. Meanwhile, apremilast (Otezla), the PDE4 inhibitor used as an active control in both Latitude studies, produced sPGA 0/1 rates of approximately 30% — roughly half the rate seen with zasocitinib in the same trials.

The oral psoriasis market has expanded substantially since deucravacitinib's FDA approval in September 2022, but neither approved oral agent — apremilast nor deucravacitinib — has matched the skin clearance rates of leading injectable IL-17 and IL-23 biologics such as risankizumab (AbbVie's Skyrizi) or bimekizumab (UCB's Bimzelx). Zasocitinib's week-16 PASI 90 rates of approximately 52%-61% begin to close that gap, though the absence of a direct biologic comparator arm in the Latitude studies limits conclusions about relative positioning against injectable therapies.

Takeda said it is on track to submit a New Drug Application to the US FDA and other regulatory authorities beginning in fiscal year 2026. The company also has a recruiting Phase III program in psoriatic arthritis and ongoing Phase II studies in Crohn's disease, ulcerative colitis, vitiligo, and hidradenitis suppurativa, signaling a broader inflammatory disease strategy built around TYK2 inhibition.

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