Evaluation of daily patch application duration for epicutaneous immunotherapy for peanut allergy David M. Fleischer, M.D., 1 Jonathan M. Spergel, M.D., Ph.D., 2 Edwin H. Kim, M.D., 3 Dianne E. Campbell, M.D., Ph.D., 4,5 Todd D. Green, M.D., 4,6 Katharine J. Bee, Ph.D., 4 Romain Lambert, M.S., 4 Terrance Ocheltree, Ph.D., 7 and Hugh A. Sampson, M.D. 4,8 ABSTRACT Background: Epicutaneous immunotherapy is a potential novel immunotherapy that utilizes unique cutaneous immuno- logic properties. In a phase III, randomized, double-blind, placebo controlled clinical trial, an epicutaneous patch (DBV712) with 250 mg of peanut protein applied once daily for 12-months was statistically superior to placebo in desensitizing children with peanut allergy (ages 4–11 years) (N = 356). Objective: To assess the relationship between the hours of daily application time and the efficacy of DBV712 250 mg. Methods: DBV712 250 mg was applied to 30 nonallergic volunteers for various durations from 2 to 24 hours and then assayed for residual peanut protein. Patch application data from the phase III clinical trial were analyzed post hoc according to prespecified responder rates and changes in the eliciting dose (ED), as measured by the geometric mean (GM) ED ratio (12 months/baseline). Results: Following application, there was a marked decrease in peanut protein on the patches from 2 to 12 hours. After 12 hours, the median peanut protein recovered was below quantification limits. The median daily patch application duration in subjects from the phase III clinical trial was 21.1 hours (DBV712 250 mg) and 22.4 hours (placebo). Ninety-five percent of the treated population achieved >10 hours per day mean application. Response rates and GM ED ratios were similar among sub- jects across a range of application durations; e.g., in those with a mean duration of >10 hours, the response rate was 36.6% and the GM ED ratio was 3.8, comparable with 42.6% and 4.0, respectively, in those with a mean duration of >20 hours. In DBV712 250 mg subjects with >16 hours mean application duration (84.5% of the treated population), the response rate was 38.8% versus 13.4% for placebo (difference, 24.4% [95% confidence interval, 15.5–34.0%]; p < 0.001). Conclusion: An evaluation of residual peanut protein on patches following application and post hoc analysis of phase III data strongly suggest that allergen delivery is attained with 12–16 hours of daily patch application time, sufficient to drive clinically meaningful desensitization to peanut after 12 months. (Allergy Asthma Proc 41:278–284, 2020; doi: 10.2500/aap.2020.41.200045) I nvestigational epicutaneous immunotherapy (EPIT) is a novel form of immunotherapy that utilizes the unique immune properties of the skin to deliver aller- gen directly to antigen-presenting cells (APC) in the epidermis and dermis, which in turn initiates a process of desensitization. 1–3 Delivery of the allergen to the epidermis is achieved by an epicutaneous patch sys- tem that creates a condensation chamber, with a roof of occlusive film electrostatically coated with peanut protein, held above the skin by a circular crown of ad- hesive foam (Fig. 1). This chamber allows natural transepidermal water loss and perspiration to From the 1 Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado; 2 Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 3 University of North Carolina School of Medicine, Chapel Hill, North Carolina; 4 DBV Technologies, Montrouge, France; 5 Children’s Hospital at Westmead, Sydney, Australia; 6 University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; 7 Certara, Princeton, New Jersey; and 8 Icahn School of Medicine at Mount Sinai, New York, New York D.M. Fleischer has received research support to his institution from DBV Technologies and Aimmune Therapeutics; reports clinical medical advisory board membership with DBV Technologies; has served as a consultant for DBV Technologies, AllerGenis, Aquestive Therapeutics, Aravax, Genentech, Nasus, and Intrommune Therapeutics; has received honorarium for lectures from DBV Technologies, and receives royalties from UpToDate. J.M. Spergel reports consultancy fees from DBV Technologies, Sanofi/Regeneron, Kaleo, and Novartis; speaker fees from Abbott and Regeneron; royal- ties from UpToDate, and grants to his institution from DBV Technologies, Aimmune Therapeutics, Sanofi/Regeneron, the National Institutes of Health (NIH), Food Allergy Research and Education (FARE), and End Allergies Together. E.H. Kim reports con- sultancy with Aimmune Therapeutics, DBV Technologies, AllerGenis, Allakos, Ukko, ExVivo Labs, and Vibrant America; clinical medical advisory board membership with DBV Technologies; and receipt of grant funding from the NIH/National Institute of Allergy and Infectious Diseases (NIAID), the NIH/National Center for Complementary and Integrative Health, FARE, and the Wallace Research Foundation. T. Ocheltree reports consultancy for DBV Technologies. H.A. Sampson is an employee of DBV Technologies, reports receiving consultancy fees from N-Fold Therapeutics, grant funding from the NIH/NIAID, and royalties from Elsevier. D.E. Campbell, T.D. Green, K.J. Bee, and R. Lambert are employees of DBV Technologies The study was sponsored by DBV Technologies Medical Creative Partners (formerly CréaBio Rhône-Alpes) assisted in the recruitment of participants for the SOLAR study. Stef Koppelman, Ph.D., a consultant for DBV Technologies, provided input to the study methodology. Aurélie Peillon, an employee of DBV Technologies, provided statistical support Address correspondence to David M. Fleischer, M.D., Children’s Hospital Colorado, 13123 E 16th Ave, Box B518, Aurora, CO 80045 E-mail address: david.fleischer@childrenscolorado.org Copyright © 2020, OceanSide Publications, Inc., U.S.A. 278 July 2020, Vol. 41, No. 4 DO NOT COPY