VIENNA — In the first head-to-head trial of two oral tyrosine kinase 2 (TYK2) inhibitors used to treat plaque psoriasis, zasocitinib was 2.5 times more effective than deucravacitinib (Sotyktu) at helping patients achieve the highest bar of efficacy, a Psoriasis Area and Severity Index (PASI) 100.

At 16 weeks, the primary endpoint of PASI 100 — which indicates that psoriatic skin is completely free of erythema, induration or infiltration, and shedding or scaling — was achieved by 36.5% of the 301 patients treated with zasocitinib vs 13.9% of the 303 treated with deucravacitinib (P < .001).

Even higher percentages of patients treated with zasocitinib vs deucravacitinib achieved key secondary endpoints, such as an absolute PASI ≤ 2 (66.1% vs 38.0%), PASI 90 (62.5% vs 34.0%), and a static Physician’s Global Assessment (sPGA) of 0 (43.2% vs 18.5%); all of these results were significant (P < .001).

Zasocitinib “was shown to be superior in terms of getting those high endpoints, including a PASI 100, PASI 90, vs deucravacitinib at week 16, and we started to see responses early on,” said Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health in Detroit, Michigan, who was principal investigator for the LATITUDE Atlas study. She presented the results during a late-breaker session at the European Academy of Dermatology and Venereology (EADV) 2026 Congress.

Take Two TYKs

Zasocitinib is an investigational TYK2 inhibitor currently under review by the FDA and European Medicines Agency for the treatment of moderate to severe plaque psoriasis. Deucravacitinib has been available in the US since September 2022.

TYK2 is a “very important component in the central inflammatory axis for plaque psoriasis,” Stein Gold explained. Although it is a member of the JAK protein family, its effects are distinct from JAK1, JAK2, and JAK3 because it is mainly involved in regulating immune responses rather than having broader effects on biological processes such as lipid metabolism and hematopoiesis. Moreover, zasocitinib has “more than 1 million-fold greater selectivity” for TYK2 over JAK1, JAK2, or JAK3 and maintained inhibition of IL-23 "as well as other important mediators” for 24 hours. By comparison, deucravacitinib had around an 87-fold higher affinity for TYK2 over the JAKs, with the effect lasting “about 4.8 hours,” Stein Gold said.

LATITUDE Atlas

LATITUDE Atlas was designed as a standard multicenter double-blind randomized trial to directly compare once-daily oral treatment with zasocitinib 30 mg or deucravacitinib 6 mg for 16 weeks, followed by a 4-week safety assessment.

Eligibility criteria, typical for this type of trial, were adults (aged ≥ 18 years) with moderate to severe plaque psoriasis for at least 6 months and ≥ 10% of body surface area affected, baseline PASI ≥ 12, and sPGA ≥ 3. 

Patient-reported outcomes also improved; greater reductions from baseline in both Dermatology Life Quality Index and itch scores were seen with zasocitinib vs deucravacitinib.

“The overall safety and tolerability have been consistent with previous trials,” Stein Gold reported. "There were no new safety signals."

Almost 66% of patients in the zasocitinib group vs 58.7% of those in the deucravacitinib group experienced any treatment-emergent adverse event, and most were mild or moderate. Adverse events leading to discontinuation occurred in 2.6% and 2.3% of patients, respectively.

The most common adverse events with zasocitinib were nasopharyngitis (12.9% vs 9.2% for deucravacitinib), upper respiratory tract infection (11.3% vs 9.2%), dermatitis acneiform (6.0% vs 1.3%), and acne (7.3% vs 3.0%).

“It's important to note that this acne 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,” Stein Gold said.

Additional Pivotal Study Data 

Other positive data for zasocitinib were presented at the congress from the pivotal LATITUDE-PsO-3001 and 3002 trials. April Armstrong, MD, professor and chief of dermatology at the University of California, Los Angeles, reported data demonstrating the durable efficacy of zasocitinib for up to 5 years. Melinda Gooderham, MD, of Queen’s University and Probity Medical Research, Peterborough, Ontario, reported the "rapidity of onset of response" seen with the drug and the effect on patients’ quality of life.

Armstrong said that more than 90% of patients who continued zasocitinib from week 40 through week 60 in LATITUDE-PsO-3002 maintained sPGA 0/1, PASI 75, or PASI 90 responses over the remaining 5 months. Additionally, more than half of patients maintained these responses after zasocitinib was stopped.

Gooderham highlighted the fact that a response to zasocitinib was evident within the first 4 weeks of treatment, with patients experiencing rapid improvements in skin and quality of life as well as reduction in symptoms and signs of disease, including itch.

Paradigm-Changing Potential

“It's an incredibly exciting time because this is the first time now that we have oral therapies that are hitting endpoints — PASI 75, PASI 90, PASI 100 — which are getting to the level of [injected] biologic therapies, and this is meaningful to patients,” Richard Langley, MD, told Medscape News Europe.

Langley, who is a professor of medicine and director of research in the Division of Clinical Dermatology & Cutaneous Science at Dalhousie University in Halifax, Nova Scotia, Canada, said he believes these new oral drugs are going to “change the paradigm” and “the way that we treat patients with psoriasis.”

Going forward, he wants to see more data on the long-term durability of effects of zasocitinib “because it is an oral medication that people have to take every day, and [we need] to make sure the adherence is there.”

Site-specific data (hand, foot, and scalp psoriasis) are ideally needed, he continued. “We know that the patients who have predominantly hand and foot disease, for example, depending on whether it's plaque or pustular, can respond differently than that population that has it as part of widespread psoriasis,” said Langley.

“I think that small molecules have great potential in this area, particularly because of the way that they're taken, their potential for penetration, and their mechanism of action,” he added.

The studies were funded by Takeda. Stein Gold was the principal investigator for LATITUDE Atlas and has served as a consultant, investigator, and/or speaker for Takeda, among other companies. Armstrong and Gooderham also disclosed relationships with Takeda, among other companies. Langley was not involved with the studies. 

Sara Freeman, BSc, MSc, is a freelance medical journalist based in London, UK. She has been reporting for specialist healthcare news organizations for more than 20 years.