in a phase 2b, randomized trial, Howard Sofen, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
The once-daily drug proved effective for this challenging condition, regardless of whether an individual’s chronic hand eczema was driven chiefly by irritant contact dermatitis, allergic contact dermatitis, or atopic dermatitis, added Dr. Sofen, medical director of Dermatology Research Associates, Los Angeles, and chief of the dermatology division at LA County/Olive View Medical Center.
Gusacitinib is a once-daily oral inhibitor of Janus kinase 1, 2, and 3, tyrosine kinase 2, and spleen tyrosine kinase (SYK). As such, it targets the Th1, Th2, Th17, and Th22 cytokine pathways, as well as SYK-mediated interleukin-17 signaling of keratinocyte proliferation and differentiation. Thus, its spectrum of activity makes it a candidate for the treatment of a variety of other inflammatory dermatologic diseases, although chronic hand eczema alone affects an estimated 7 million Americans, the dermatologist noted.
The phase 2b, double-blind, 16-week, multicenter, randomized trial included 97 patients who were randomized to oral gusacitinib as monotherapy at 40 or 80 mg once daily or placebo. All participants had chronic hand eczema of more than 6 months duration that was refractory to potent or superpotent topical and/or systemic steroids. Participants were split 60/40 between those with severe chronic hand eczema, defined by a baseline score on the 0-4 Physician’s Global Assessment scale, and moderate disease, with a PGA of 3.
The primary endpoint was the percent improvement in modified total lesion severity score (mTLSS) at week 16 from a mean baseline of 13.2. A clearcut dose response was evident: Gusacitinib at 80 mg/day achieved a 69.5% decrease, while 40 mg brought a 40% reduction, which wasn’t significantly better than the 33.5% decrease in placebo-treated controls.
The rapidity of response was noteworthy in these steroid-refractory patients. The 80-mg group showed significant separation from placebo by 2 weeks, with a mean 40.1% reduction in mTLSS versus 13.6% with placebo.
The secondary endpoint was achievement of a PGA score of 0 or 1 – that is, clear or almost clear – with a 2-grade improvement over placebo. This was achieved in 31.3% of patients assigned to the higher dose of gusacitinib at week 16, a success rate fivefold higher than the 6.3% rate in controls. The two groups separated on this endpoint at week 2, the first assessment. At week 8 there was an eightfold difference in response: 25% in patients on gusacitinib at 80 mg, 3.1% with placebo.
The other secondary endpoint was improvement in itch as measured by the mTLSS pruritus 0-3 subscore. As for the other outcomes, the improvement in itch was rapid. At week 2, patients on gusacitinib at 80 mg averaged a 43.1% reduction from their baseline pruritus score, compared with 4.6% with placebo. At week 16, the reductions were 65.7% and 29.8%, respectively.
Both doses of gusacitinib were well tolerated, according to Dr. Sofer. No thromboembolic events, major adverse cardiovascular events, or opportunistic infections occurred during the short 16-week study. The drug’s safety profile was consistent with what’s been seen in a collective gusacitinib clinical trial experience totaling more than 350 patients: mild to moderate nasopharyngitis, headache, asymptomatic elevations in creatine phosphokinase, and a slight increase in HDL cholesterol accompanied by a small reduction in LDL cholesterol.
Dr. Sofen reported receiving research funding from and serving as a consultant to Asana BioSciences, the study sponsor, as well as more than half a dozen other pharmaceutical companies.