Trial Results Promising for Atopic Dermatitis Remedy

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A novel compound has emerged from two phase clinical trials as a promising topical treatment for mild to moderate atopic dermatitis (AD).

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Crisaborole (Anacor Pharmaceuticals), a nonsteroidal phosphodiesterase 4 (4) inhibitor, showed safety and efficacy in two identically designed, vehicle-controlled double-blind studies reported by lead author Amy Paller, MS, MD, Northwestern University, Feinberg School of Medicine, Chicago and colleagues in a July 7 online post of the Journal of the American Academy of Dermatology.

The populations of the two trials were drawn from patients aged 2 years or older, with mild to moderate AD involving 5 percent or more treatable body surface. A combined total of over 1,000 patients received the active agent and over 500 the inactive vehicle, applied twice daily to affected areas throughout the 28-day study period.

The efficacy end point of success at day 29, defined as clear (0) or almost clear (1) on the Investigator's Static Global Assessment (ISGA) with a 2-grade or more improvement from baseline, was demonstrated by 32.8 percent of patients in one trial and 31.4 percent in the other, compared to 25.4 percent and 18 percent with the inactive vehicle. Treatment-related adverse events were characterized as infrequent, and mild to moderate in severity.

"The significant efficacy of crisaborole versus vehicle was noted," Paller and colleagues commented, "despite a strong 'vehicle effect' ...which is a common phenomenon in AD clinical studies that compare active therapeutics with their emollient bases."

A New Drug Application (NDA) for crisaborole was filed with the FDA in March 2016, and the review by the agency is expected to be completed by January 2017, consistent with terms of the Prescription Drug User Fee Act.

Paller and colleagues reflected that while topical treatments are commonly prescribed to alleviate AD symptoms, "no new molecules have been approved for the treatment of AD in the past 15 years."

The prospect of a new drug action which appears effective against the itch and inflammation of AD suggests new research directions to identify and remediate underlying disease mechanisms, according to an accompanying commentary by Jon Hanifin MD, Department of Dermatology, Oregon Health and Science University.

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"We are now in an exciting era of long-overdue advances for therapy of AD," Hanifin observed. "The new 4 inhibitor drugs may also, hopefully, provide for early proactive therapy to prevent both the advancing, prolonged eczema and the consequent food and respiratory allergies that so often follow skin disease."