Linda Stein Gold, MD, discusses LATITUDE Atlas data showing zasocitinib achieved higher PASI 100 rates than deucravacitinib in psoriasis.
Zasocitinib, an investigational next-generation tyrosine kinase 2 (TYK2) inhibitor, may allow clinicians to aim for completely clear skin with an oral agent for
Stein Gold, principal investigator of the phase 3 LATITUDE Atlas trial, discussed head-to-head data presented at the
In LATITUDE Atlas, 36.5% of patients receiving zasocitinib achieved a 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 16, compared with 13.9% receiving deucravacitinib (P < .001), according to Takeda.¹ Stein Gold noted the trial was the first head-to-head comparison of 2 drugs sharing the same mechanism of action, and the first to use PASI 100 as its primary endpoint. Based on the data so far, she said zasocitinib appears to perform similarly to traditional biologics.
Despite their shared mechanism, Stein Gold described the 2 agents as quite different. She cited more than 1 million-fold greater selectivity for TYK2 over Janus kinase (JAK) 1, 2, and 3 with zasocitinib, compared with roughly 87-fold with deucravacitinib, a distinction aimed at avoiding off-target metabolic or hematologic effects.¹ She also pointed to the duration of interleukin (IL)-23 blockade, which extends over 24 hours with zasocitinib versus just under 5 hours with deucravacitinib.
Higher rates of complete clearance with zasocitinib emerged as early as week 8.² Stein Gold explained oral agents have historically taken time to show an effect, which has required considerable reassurance for patients. Visible improvement within the first several weeks gives patients confidence to continue treatment, even before their skin is fully clear.
In the pivotal LATITUDE PsO 3001 and 3002 studies, up to 93% of week 24 responders maintained skin clearance through week 52 or week 40, and patients reported improvements in itch and quality of life as early as week 2.¹ Stein Gold emphasized itch as a central component of psoriasis for many patients, contributing to poor sleep and diminished quality of life. The goal, in her view, is for patients to live as people with psoriasis rather than living their lives around the disease.
Patients want to gain control of their disease and keep it, Stein Gold added, and they need confidence their medication can deliver both over time.
Stein Gold noted clinicians have not always presented an oral option to patients with moderate to severe plaque psoriasis, since no oral drug previously combined adequate efficacy, tolerability, and safety. With next-generation TYK2 inhibitors and other recently approved oral agents, she now offers these medications as a first-line option for patients not responding to topical therapy. Zasocitinib remains under review by the US Food and Drug Administration and the European Medicines Agency.¹
The most common adverse events across the LATITUDE program were upper respiratory tract infection, nasopharyngitis, and acne.¹ Stein Gold observed acne occurred more often with zasocitinib than with placebo and slightly more often than with deucravacitinib, although most cases were mild to moderate and many resolved without treatment. She recommended counseling patients up front about the possibility of acne, noting dermatologists can manage it, often with topical therapy alone.
Editor’s note: This summary has been edited for grammar and clarity using artificial intelligence tools. Financial disclosures reported for Stein Gold include AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Organon Health, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB.
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