乌鸦传媒

Zasocitinib, a tyrosine kinase 2 (TYK2) inhibitor, holds promise as a new oral treatment for psoriasis, randomized clinical trial data suggest.

Results of the multisite phase 2b trial, which appeared in , presented data from 259 patients with moderate-to-severe plaque psoriasis who were randomized to receive zasocitinib at different dosage levels or placebo.

At week 12 of the trial, the PASI 75 clinical threshold was achieved by 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients who received zasocitinib at 2, 5, 15, and 30 mg, respectively. Meanwhile, PASI 75 was achieved by 3 patients (6%) receiving placebo. Similar findings emerged for PASI 90 and PASI 100 responses at various doses of zasocitinib.

The trial was conducted at 47 centers in the U.S. and eight in Canada. The following paper excerpts were edited for length and clarity.

What was the intent of this study?

Injectable biologics have proven effective in treating plaque psoriasis. However, relatively few oral therapies have been investigated, and none have shown the same levels of efficacy, safety, and tolerability as currently available biologics.

TYK2 inhibitors are a promising target for novel oral agents in treating psoriasis and other immune-mediated diseases. Deucravacitinib, an oral allosteric TYK2 inhibitor recently approved by the FDA for treating moderate-to-severe psoriasis, has set the clinical precedent for selectively targeting TYK2 activity in psoriasis.

Zasocitinib (formerly TAK-279) is an oral, allosteric TYK2 inhibitor. Although its mechanism of action is identical to that of deucravacitinib, zasocitinib was identified via a computationally enabled design strategy and demonstrates a higher level of selectivity than deucravacitinib.

A previous phase 1 study demonstrated that zasocitinib has a safety profile consistent with TYK2 inhibition. In the present phase 2b randomized clinical trial, researchers assessed the efficacy, safety, and tolerability of zasocitinib at various doses in patients with moderate to severe psoriasis.

What were the findings on the efficacy of zasocitinib?

The trial's primary endpoint of PASI 75 response at week 12 was achieved by patients receiving zasocitinib at doses of 5 mg and higher. A trend for a dose-response association was observed for PASI 75 and 90 in patients taking zasocitinib at 15 mg, with similar efficacy achieved at 30 mg.

What were the safety findings?

Efficacy and safety results from the current study were consistent with previous studies on zasocitinib.

The incidence of treatment-emergent adverse events (TEAEs) was higher in the zasocitinib groups compared with placebo, but there was no clear dose dependence for any individual TEAE.

TEAEs occurred in 28 (53%) to 31 (62%) patients receiving the four different doses of zasocitinib. The incidence of TEAEs of 44% in the placebo arm aligned with previous clinical trial results of treatments in plaque psoriasis.

COVID-19, acne/acneiform dermatitis, and diarrhea were the most frequently reported TEAEs. No treatment-related serious adverse events, opportunistic infections, or psychiatric sequelae were reported during the study.

What are the key take-away messages?

According to researchers, zasocitinib is an advanced, potent, and highly selective oral TYK2 inhibitor bioengineered to optimize target coverage and functional selectivity. During this trial, zasocitinib achieved biologic-level efficacy with complete skin clearance observed after only a 12-week treatment period in up to one-third of patients.

The drug had a low incidence of known tolerability issues and an absence of serious toxic effects that are characteristic of JAK1-3 inhibition. Two phase 3 studies of longer duration and with larger populations (NCT06088043 and NCT06108544) have been initiated to confirm prior observations.