Novel Topical Agent Reduces Chronic Itch

Selected by Pietro Cazzola

PruritusISTANBUL, TURKEY – A first-in-class topical tyrosine kinase inhibitor markedly reduced chronic pruritus in psoriasis patients in a phase-IIb study.
Moreover, the investigational agent, known for now as CT327, produced no application site reactions or indeed any other adverse events. Nor was it absorbed systemically, Dr. David Roblin reported at the annual congress of the European Academy of Dermatology and Venereology.
A significant unmet need exists for safe and effective therapies for chronic itching, not only in psoriasis but in other diseases for which chronic pruritus figures prominently and has a debilitating effect on quality of life. At present, there is no medication with an indication for treatment of chronic pruritus, noted Dr. Roblin, chief medical officer at Creabilis in Canterbury, England.
Tyrosine kinase is a high-affinity receptor of nerve growth factor. Thus, CT327 targets the sensory neurons implicated in the pathogenesis of chronic pruritis, he explained.
The multicenter, randomized, double-blind clinical trial included 160 patients with mild-to-moderate psoriasis affecting up to 10% of their body surface area. They were assigned to twice-daily application of CT327 at 0.05%, 0.1%, or 0.5% or to the vehicle for 8 weeks. Participants treated all their plaques except those on the face or scalp.
The safety assessment included all 160 patients; however, efficacy endpoints were assessed only in the 108 with at least moderate baseline pruritus as defined by a score greater than 40 mm on a 0-100 mm visual analog scale (VAS).
From a baseline mean pruritus VAS of 65.2, scores decreased at week 8 by 37.1 mm in the CT327 0.05% group, 31.5 mm in patients using CT327 0.1%, 36.4 mm in the 0.5% group, and 16.1 mm in vehicle-treated controls. A 20-mm reduction on the VAS is considered clinically meaningful. Four weeks after treatment stopped, pruritus scores had returned to baseline.
The 108 patients with at least moderate baseline pruritus had a baseline mean Psoriasis Area and Severity Index score, modified to exclude the untreated face and scalp (mPASI), of 9.3. At 8 weeks, patients in the CT327 0.05%, 0.1%, and 0.5% groups averaged mPASI score reductions of 46%, 36%, and 37%, respectively, compared with a 17% drop in the control group.
Of note, there was no correlation between baseline mPASI and pruritus severity scores, which suggests that trying to treat pruritus with agents directed at the inflammatory aspect of psoriasis may be a suboptimal strategy. It’s better to target the sensory neurons involved in the itch, according to Dr. Roblin.

The study was sponsored by Creabilis, which is developing CT327. Dr. Roblin is the company’s medical director.

B Jancin