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Zasocitinib Outperforms Deucravacitinib in Psoriasis Trial

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In Short: In a head-to-head trial, zasocitinib showed superior efficacy in treating moderate to severe plaque psoriasis compared to deucravacitinib.

In a head-to-head trial, zasocitinib demonstrated superior efficacy in treating moderate to severe plaque psoriasis compared to deucravacitinib, achieving a PASI 100 score in 36.5% of patients versus 13.9% for deucravacitinib at 16 weeks.

Principal investigator Linda Stein Gold, MD, noted that zasocitinib's higher selectivity for TYK2 over JAKs contributes to its effectiveness, with a more than 1 million-fold greater selectivity for TYK2.

Patient-reported outcomes also favored zasocitinib, with greater reductions in the Dermatology Life Quality Index and itch scores compared to deucravacitinib.

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

Melinda Gooderham, MD, highlighted the rapid onset of response and the positive impact on patients' quality of life with zasocitinib.

Richard Langley, MD, emphasized the significance of oral therapies achieving PASI 75, PASI 90, and PASI 100 scores, which are comparable to biologic therapies.

April Armstrong, MD, presented data showing that more than 90% of patients who continued zasocitinib from week 40 to week 60 maintained PASI 75, PASI 90, or sPGA 0/1 responses over the remaining 5 months.

The overall safety and tolerability of zasocitinib were consistent with previous trials, with mild to moderate acne that resolved without stopping treatment.

Zasocitinib is currently under review by the FDA and European Medicines Agency for the treatment of moderate to severe plaque psoriasis, while deucravacitinib has been available in the US since September 2022.

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• TYK2 is a “very important component in the central inflammatory axis for plaque psoriasis,” Stein Gold explained.
• “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.
• 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.
• “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.
• 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).
• 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.

Sources

• Medscapelink