Oral Zasocitinib Demonstrates Safety and Efficacy in Moderate to Severe Plaque Psoriasis

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A recent phase 2b clinical trial of zasocitinib, a selective oral TYK2 inhibitor, has shown promising results for patients with moderate to severe plaque psoriasis. The study found that zasocitinib achieved high efficacy in reducing psoriasis symptoms, with up to one-third of patients experiencing complete skin clearance after 12 weeks of treatment.

Importantly, the treatment demonstrated a favorable safety profile with no serious adverse events commonly associated with broader Janus kinase (JAK) inhibitors.

This randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial is published in JAMA Dermatology.

"For patients with psoriasis, I think offering them multiple different options in terms [of] how they would like to take their medications is really important, whether it's topical, oral, or biologics—which are mostly injectables," said study author April Armstrong, MD, MPH, professor and chief of dermatology, UCLA, to The American Journal of Managed Care (AJMC).

The trial was conducted across 47 centers in the US and 8 centers in Canada from August 11, 2021, to September 12, 2022. Patients were randomly assigned 1:1:1:1:1 ratio to receive 1 of 4 oral doses of zasocitinib (2 mg, 5 mg, or 30 mg) or placebo, once daily for 12 weeks, followed by a 4-week safety monitoring period. Randomization was stratified based on previous treatment with biologics.

Participants were adults aged 18 to 70 years with moderate to severe plaque psoriasis for at least 6 months and were candidates for systemic or phototherapy. Additionally, patients with other forms of psoriasis, active infections, or recent use of treatments that could affect psoriasis within 2 to 4 weeks before baseline were excluded.

The primary end point was the proportion of patients achieving a 75% or greater improvement from baseline in Psoriasis Area and Severity Index (PASI 75) score at week 12. Secondary endpoints were the proportion of patients achieving PASI 90 and PASI 100, a Psoriasis Global Assessment (PGA) score of clear (0) or almost clear (1), and changes in Dermatology Life Quality Index (DLQI) from baseline.

Additionally, safety end points included incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs, clinical laboratory parameters, and electrocardiograms.

A total of 259 patients were included in the study, with a mean (SD) of 47 (13) years and 82 (32%) women. PASI 75 response at week 12 was achieved among the following groups:

• Zasocitinib 30 mg: 48.9%
• Zasocitinib 15 mg: 30.4%
• Zasocitinib 5 mg: 13.7%
• Zasocitinib 2 mg: 8.2%
• Placebo: 4.3%

Furthermore, the 30-mg dose showed a statistically significant higher proportion of patients achieving PASI 75 compared with placebo (P < .001).

PASI 90 responses were consistent with PASI 75, while PASI 100 demonstrated a dose response at all doses, with 17 (33%) patients achieving PASI 100 with zasocitinib 30 mg.

TEAEs occurred for 23 (44%) patients receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib. No dose dependency and no clinically meaningful longitudinal differences in laboratory parameters were observed.

However, the researchers acknowledged some limitations, such as a small sample size and short study duration. Additionally, less than 8% of the patient population was Black, and the study was conducted only at centers in North America with a restricted range of patient weights and body mass indices.

Despite these limitations, the researchers believe the study highlights the potential of zasocitinib in achieving biologic-level efficacy with complete skin clearance after only 12 weeks of treatment.

"This particular study focusing on a TYK2 inhibitor with good efficacy and safety profile will offer patients another oral therapy, which many of our patients with moderate to severe psoriasis also prefer to have that option available," said Armstrong. "I think that will increase their likelihood [of] also adhering to the therapy by choosing a route of administration that many of our patients prefer."

Reference

Armstrong AW, Gooderham M, Lynde C, et al. Tyrosine kinase 2 inhibition with zasocitinib (TAK-279) in psoriasis: A randomized clinical trial. JAMA Dermatol. Published online August 21, 2024. doi:10.1001/jamadermatol.2024.2701

[This article was originally published by our sister publication, American Journal of Managed Care.]