Maximal use systemic exposure study evaluating AN2728, a novel boron-based small molecule, for the treatment of pediatric and adolescent subjects with mild-to-moderate atopic dermatitis (THER2P.959)

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (1_Supplement), p.67-67.10
• Main Authors: Kircik, Leon, Call, Robert, Tschen, Eduardo, Draelos, Zoe, Van Syoc, Merrie, Zane, Lee, Hebert, Adelaide
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.67.10

AN2728, a novel boron-based compound, inhibits phosphodiesterase-4 and reduces proinflammatory cytokine production possibly associated with atopic dermatitis(AD). This open-label maximal-use study evaluated systemic exposure, PK, and safety of AN2728 Ointment, 2% BID for 28 days in children and adolescents with mild-to-moderate AD(N=34; 3 cohorts based on age and minimum % treatable body surface area [%BSA] affected: 2-5y [≥35%]; 6-11y [≥35%]; 12-17y [≥25%]). Disease severity was measured using Investigator’s Static Global Assessment (ISGA; 0, clear to 4, severe), signs/symptoms score (0, none to 3, severe) and %BSA affected. At day 29, 65% of subjects had ISGA scores of clear or almost clear and 47% had scores of clear or almost clear and a ≥2-grade improvement vs baseline. Marked reductions vs baseline were seen for AD signs and symptoms (pruritus, erythema, lichenification, excoriation, exudation) throughout treatment. Mean pruritus scores improved by ~60% vs baseline as early as treatment day 5. Mean %BSA affected decreased by 78% after 4 weeks of treatment. The most common treatment-related adverse events were application site reactions (n=12) which generally were mild or moderate and resolved spontaneously. One patient withdrew due to application site pain. PK results showed low AN2728 blood levels similar to those previously seen in adults after adjusting for %BSA treated. AN2728 Ointment, 2% may be safe and effective in subjects aged ≥2 years with mild-to-moderate AD.