In the treatment of moderate-to-severe plaque psoriasis, the investigational selective tyrosine kinase 2 (TYK2) inhibitor zasocitinib is associated with higher rates of skin clearance compared with the first-generation TYK2 inhibitor deucravacitinib, as shown in the head-to-head phase III LATITUDE Atlas trial.
Patients treated with zasocitinib were more than 2.5 times more likely to achieve the primary efficacy endpoint of complete skin clearance (100-percent improvement in Psoriasis Area and Severity Index [PASI]) compared with those who received deucravacitinib, reported principal investigator Dr Linda Stein Gold from Henry Ford Medical Center, Detroit, Michigan, US, at the annual EADV congress.
“We found a separation [between zasocitinib and deucravacitinib] after week 4 that continued and improved over 16 weeks,” Stein Gold noted.
PASI 100 response rates were 12.3 percent with zasocitinib vs 4.3 percent with deucravacitinib at week 8 (p<0.001), 23.3 percent vs 8.9 percent at week 12 (p<0.001), and 36.5 percent vs 13.9 percent at week 16 (p<0.001; primary endpoint). [EADV 2026, abstract 312]
Results for key secondary efficacy endpoints showed a similar pattern, with between-group differences observed as early as week 8 and maintained through week 16. At week 16, 62.5 percent of participants in the zasocitinib group vs 34 percent in the deucravacitinib group achieved PASI 90 response, 66.1 percent vs 38 percent had an absolute PASI score of ≤2, and 43.2 percent vs 18.5 percent had a static Physician’s Global Assessment score of 0.
Compared with deucravacitinib, zasocitinib was also associated with greater improvements in Dermatology Life Quality Index (DLQI) and Itch Numerical Rating Scale (NRS) scores at week 16. DLQI score decreased by 9.51 points from a baseline of 13.4 in the zasocitinib group vs by 7.62 points from a baseline of 13.1 in the deucravacitinib group, while itch NRS decreased by 3.96 points from a baseline of 6.3 vs by 3.22 points from a baseline of 6.7 in the respective groups.
“So, these drugs are actually improving patients’ lives, with a better improvement on zasocitinib,” Stein Gold noted.
Safety
As for safety, “the results from this clinical trial were very similar with data from previous trials, with no new safety signals,” Stein Gold said.
Treatment-emergent adverse events (TEAEs) occurred in 65.9 percent of patients in the zasocitinib group and 58.7 percent in the deucravacitinib group. These events were mild or moderate in severity, with the most common being nasopharyngitis, upper respiratory tract infection, acne, and dermatitis acneiform.
Stein Gold acknowledged a higher signal for acne with zasocitinib but noted that this event was mild to moderate. “It went away either with medication or without medication, and no patients in this particular clinical trial stopped treatment because of their acne,” she said.
TEAEs led to treatment discontinuation in 2.6 percent of patients in the zasocitinib group and 2.3 percent in the deucravacitinib group. Serious adverse events occurred in 1.3 percent and 2.3 percent of patients in the respective group. There was one death in the zasocitinib group that was deemed unrelated to the drug. No clinically meaningful trends were observed in laboratory parameters through week 16 in either of the groups.
LATITUDE Atlas
“LATITUDE Atlas is the first head-to-head trial in dermatology to directly compare two agents with an identical mode of action, as well as the first psoriasis trial of oral agents to use the stringent measure of PASI 100 as the primary endpoint,” said Stein Gold.
Stein Gold pointed out that zasocitinib differs from deucravacitinib in both the magnitude of TYK2 selectivity and duration of action. Zasocitinib has more than 1-million-fold greater selectivity for TYK2 vs Janus kinase (JAK) 1/2/3 and maintains inhibition of IL-23 and other core disease-driving immune pathways for 24 h, she noted. In contrast, deucravacitinib has 87-fold higher selectivity for TYK2 over the JAKs, with the IL-23 inhibition lasting around 4.8 h, she added.
“We have this abundance of new potential oral drugs, and we are seeing the triad of better efficacy, better tolerability, and good safety with these new medications,” Stein Gold said. “Zasocitinib is still in clinical trials, but with approval, we will have an option that actually gives us that very high level of efficacy in an oral once-daily option.”
LATITUDE Atlas included 604 patients (average age 46 years, 66.9 percent male, 82.1 percent White) with PASI score of ≥12, sPGA score of ≥3, and body surface area involvement of ≥10 percent at baseline. These patients were randomly assigned to treatment with either zasocitinib 30 mg (n=301) or deucravacitinib 6 mg (n=303), taken orally once a day.
At baseline, PASI score was between 19 and 19.7, sPGA score was 3 in 83.8 percent of patients, and body surface area was between 22 percent and 23.3 percent.