SAN FRANCISCO– An investigational topical ointment met its safety endpoints and showed signs of efficacy in children and adolescents with mild to moderate atopic dermatitis, according to a small phase II study.
Four weeks of twice-daily treatment with the AN2728 agent yielded an average 78% reduction in affected body surface area, reported Dr. Zoe Draelos at the annual meeting of the American Academy of Dermatology.
At day 29, 65% of patients had achieved Investigator’s Static Global Assessment (ISGA) scores of clear or almost clear, and 47% of patients had achieved those scores plus at least a two-grade improvement from baseline, said Dr. Draelos, a dermatologist in High Point, North Carolina.
The ointment is a 2% formulation of AN2728, a small-molecule compound based on elemental boron that works by suppressing phosphodiesterase type 4 activity, which in turn inhibits the release of cytokines such as TNF-alpha, IL-12, and IL-23. Investigators assessed its safety, pharmacokinetics, and effects on the signs and symptoms of atopic dermatitis (AD), as well as changes in the percentage of body surface area affected and disease severity based on the five-point IGSA scale, ranging from 0 (clear) to 4 (severe disease).
The study enrolled 34 patients aged two to 17 years who had AD affecting 25% to 35% of body surface area. The cream was applied twice daily for 28 days, which was done in the clinic for the first eight days to ensure maximum exposure to the agent.
Plasma levels of the agent measured on days 1 and 8 were low and resembled those previously observed for adults after adjusting for the percentage of body surface area treated. Twelve of the 34 patients had application site reactions, which included paresthesia, papules, itching, and burning, most of which were mild to moderate and resolved spontaneously. However, one patient withdrew from the study because of pain at the application site.
Patients had “marked” reductions in AD signs and symptoms, Dr. Draelos reported. Pruritus scores dropped an average of 60%, with improvements starting on about day 5 of treatment that leveled off at about day 15, she added. The investigators saw similar trends for erythema, lichenification, excoriation, and exudation.
Because patients were not allowed to use emollients during treatment, the adverse events observed were directly tied to twice-daily use of the product, Dr. Draelos noted.
Researchers are enrolling patients in phase III trials of AN2728, with data expected later in 2015, according to a press release from Anacor Pharmaceuticals, which makes the agent. Two carcinogenicity studies wrapped up earlier this year and yielded no evidence of malignancies, the company also reported.
Anacor sponsored the study. Dr. Draelos reported having served as a researcher for and receiving grant support from Anacor for the work.