LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance ( ), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle ().
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.