Small molecule effective in moderate-to-severe psoriasis

In the phase 3 trials POETYK PSO-1 and POETYK PSO-2, the tyrosine kinase 2 inhibitor deucravacitinib was compared with apremilast and placebo. Deucravacitinib appeared an effective oral option for the treatment of psoriasis.

Prof. April Armstrong (Keck School of Medicine at UCLA, CA, USA) pointed out that deucravacitinib is a novel oral selective tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus Kinase inhibitors [1]. Deucravacitinib binds selectively to the TYK2 regulatory domain, thus inhibiting TYK2-mediated signalling of cytokines involved in psoriasis pathogenesis, such as IL-23, IL-12, and type-1 interferon.

The efficacy and safety of deucravacitinib were assessed in 2 global phase 3 studies, the POETYK PSO-1 (NCT03624127) and the POETYK PSO-2 (NCT03611751). Both studies included patients with moderate-to-severe psoriasis. In POETYK PSO-1, in contrast to POETYK PSO-2, patients from Asian countries including China were enrolled.

Patients were treated with deucravacitinib, the currently available treatment apremilast, or placebo. In both trials, the co-primary endpoints were the percentage of patients achieving Psoriasis Area and Severity Index (PASI) 75 and the percentage of patients achieving static Physician's Global Assessment (sPGA) score of 0 or 1 (i.e. clear or almost clear skin) at week 16 versus placebo. After this time, placebo patients, as well as patients who failed apremilast, were switched to deucravacitinib and all patients were treated to week 52 (secondary endpoint).

At week 16, significantly greater proportions of patients in the deucravacitinib compared with placebo and apremilast arms achieved PASI 75. Similarly, a greater proportion of patients in the deucravacitinib compared with placebo and apremilast arms gained sPGA 0/1 at week 16 in both trials. The selective TYK2 inhibitor was also superior to apremilast at week 24 in both trials. Of deucravacitinib-treated patients who achieved PASI 75 at week 24, 82.5% in POETYK PSO-1 and 81.4% in POETYK PSO-2 continued treatment and maintained their PASI 75 response at week 52.

“Deucravacitinib was also better in multiple secondary endpoints,” Prof. Armstrong said. Significantly more patients in the deucravacitinib arms achieved a quality of life no longer impeded by the disease (corresponding to a score of 0/1 in the Dermatology Life Quality Index). The TYK2 inhibitor also improved symptoms of psoriasis such as burning, itch, and pain. After 16 weeks, 70.8% of patients in the POETYK PSO-1 trial achieved complete or almost complete clearance of their scalp lesions, compared with 39.1% in the apremilast arm and 17.4% in the placebo arm.

The most common adverse events were nasal pharyngitis and headache. “As in previous studies, there was a mild signal for folliculitis,” Prof. Armstrong added. However, cases were mild to moderate, and only 1 patient with folliculitis discontinued deucravacitinib treatment.

1. Armstrong A, et al. Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate to severe plaque psoriasis: Results from the phase 3 POETYK PSO-1 study. Session S033, AAD VMX 2021, 23-25 April.

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Posted on 7 June 202130 June 2021