World Congress at ACG2017
Simultaneous Plenary Session 1D: Late-Breaking Abstracts
20 - Dupilumab Efficacy and Safety in Adult Patients With Active Eosinophilic Esophagitis: A Randomized Double-Blind Placebo-Controlled Phase 2 Trial
Monday, October 16
4:30 PM - 4:40 PM
Location: W414 (Level 4)
Evan Dellon, MD, MPH, FACG
Associate Professor of Medicine and Epidemiology, Center for Esophageal Diseases and Swallowing
University of North Carolina School of Medicine
Chapel Hill, NC
Category: General Endoscopy
Ikuo Hirano1*, Evan S. Dellon2*, Jennifer D. Hamilton3, Margaret H. Collins4, Kathryn Peterson5, Mirna Chehade6, Alain M. Schoepfer7, Ekaterina Safroneeva8, Marc E. Rothenberg9, Gary W. Falk10, Yehudith Assouline-Dayan11, Zhizhi Qing3, Brian N. Swanson12, Gianluca Pirozzi12, Leda Mannent13, Neil M.H. Graham3, Bolanle Akinlade3, Allen Radin3 (*Co-first authors)
1Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2University of North Carolina School of Medicine, Chapel Hill, NC, USA; 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 4Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA; 5University of Utah School of Medicine, Salt Lake City, UT, USA; 6Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 8Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; 9Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; 10University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 11University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 12Sanofi, Bridgewater, NJ, USA; 13Sanofi, Chilly-Mazarin, France
Introduction: Patients (pts) with eosinophilic esophagitis (EoE) have high rates of comorbid type 2-mediated diseases (e.g. food allergy, atopic dermatitis [AD], asthma). Due to limited response to standard of care and lack of approved medications for EoE, there is a need for new treatment options for this chronic disease. Dupilumab, a fully human anti-interleukin (IL)-4Rα monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of type 2-mediated inflammation, and is approved in the USA for the treatment of adults with moderate-to-severe AD. This study assessed the efficacy and safety of dupilumab in adults with active moderate-to-severe EoE.
Methods: was a randomized, double-blind, parallel, placebo (PBO)-controlled phase 2 study (NCT02379052). Adults with active EoE (histologically confirmed with dysphagia symptoms) were randomized (1:1) to receive weekly subcutaneous dupilumab 300 mg (loading dose 600 mg on Day 1) or PBO, for 12 weeks. The primary endpoint was change in Straumann Dysphagia Instrument (SDI) score from baseline (BL) to Week 10. Secondary endpoints included percent change in weekly Eosinophilic Esophagitis Activity Index (EEsAI) score from BL to Week 10, percent change in overall peak esophageal intraepithelial eosinophil count (eos/hpf), change in a modified EoE Endoscopic Reference Score (EoE-EREFS) from BL to Week 12, and safety. Exploratory endpoints included change in EoE Histological Scoring System (EoE-HSS) and esophageal distensibility from BL to Week 12.
Results: 47 pts (dupilumab n=23) received ≥1 dose of study drug. BL demographics and characteristics were balanced between treatment groups, except for mean total IgE (dupilumab 217.8 kU/L; PBO 468.2 kU/L). Dupilumab improved SDI score (−3 vs −1.3; P=0.0304) and numerically reduced EEsAI score (−34.6% vs −11.3%; P=0.085) vs PBO at Week 10 (Table). At Week 12, dupilumab reduced peak eosinophil count (eos/hpf) from BL by −94.1 (−91.8%) vs −7.4 (+15.1%) with PBO (P<0.0001), and decreased EoE-EREFS by −1.9 vs −0.3 with PBO (P=0.0006). Total EoE-HSS grade and stage scores and distensibility plateau were improved at Week 12 (all P<0.001 vs PBO). The most common treatment-emergent adverse events were injection-site erythema (dupilumab 34.8%; PBO 8.3%) and nasopharyngitis (dupilumab 17.4%; PBO 4.2%).
Discussion: Dupilumab significantly improved dysphagia as well as histological and endoscopic measures of disease, and was generally well tolerated in adults with EoE.
Disclosures: Does Disclose
Ikuo Hirano: Consultant - Adare Pharmaceuticals, Inc., Receptos Inc./Celgene, Regeneron Pharmaceuticals, Inc., Shire; Grant/Research Support - Meritage, Receptos Inc./Celgene, Regeneron Pharmaceuticals, Inc., Shire.
Evan S. Dellon: Consultant - Alivio, Adare Pharmaceuticals, Inc., Banner, Enumeral, GlaxoSmithKline, Receptos, Inc./Celgene, Regeneron Pharmaceuticals, Inc., Shire; Grant/Research Support: Meritage, Miraca, Nutricia, Receptos, Inc./Celgene, Regeneron Pharmaceuticals, Inc., Shire; Educational Grant - Banner.
Jennifer D. Hamilton: Employee, Shareholder - Regeneron Pharmaceuticals, Inc.
Margaret H. Collins: Consultant - Adare Pharmaceuticals, Inc., Regeneron Pharmaceuticals, Inc., Shire; Grant Research/Support - Receptos, Inc./Celgene Regeneron Pharmaceuticals, Inc., Shire.
Kathryn Peterson: Grant/Research Support - Janssen, Receptos Inc./Celgene, Regeneron Pharmaceuticals, Inc.
Mirna Chehade: Consultant - Actelion, Shire; Grant/Research Support – Nutricia, Regeneron Pharmaceuticals Inc., Shire.
Alain M. Schoepfer: Consultant - Adare Pharmaceuticals, Inc., Aptalis Pharma, Inc., Dr. Falk Pharma, GmbH; Grant/Research Support: AstraZeneca AG, Aptalis Pharma, Inc., Dr. Falk Pharma, GmbH, GlaxoSmithKline, Nestle SA, Novartis, Receptos, Inc./Celgene, Regeneron Pharmaceuticals, Inc.
Ekaterina Safroneeva: Consultant - Aptalis Pharma, Inc., Novartis.
Marc E. Rothenberg: Consultant - AstraZeneca, Celgene, GlaxoSmithKline, NKT Therapeutics, Novartis. Pulm One, Shire, Spoon Guru; Equity Interest - Immune Pharmaceuticals, NKT Therapeutics, Pulm One, Spoon Guru; Royalties from Reslizumab - Teva Pharmaceuticals; Inventor of Patents Owned by the Hospital: Cincinnati Children's Hospital Medical Center.
Gary W. Falk: Consultant – Adare Pharmaceuticals, Inc.; Grant/Research Support – Adare Pharmaceuticals, Inc., Meritage, Receptos Inc.,/Celgene, Regeneron Pharmaceuticals, Inc., Shire.
Yehudith Assouline-Dayan: Nothing to disclose.
Zhizhi Qing: Contract Statistician - Regeneron Pharmaceuticals, Inc.
Brian N. Swanson: Employee, Stock Options - Sanofi.
Gianluca Pirozzi: Employee, Stock Options - Sanofi.
Leda Mannent: Employee, Stock Options - Sanofi.
Neil M. H. Graham: Employee, Shareholder - Regeneron Pharmaceuticals, Inc.
Bolanle Akinlade: Employee, Shareholder: Regeneron Pharmaceuticals, Inc.
Allen Radin: Employee, Shareholder: Regeneron Pharmaceuticals, Inc.
Citation: . DUPILUMAB EFFICACY AND SAFETY IN ADULT PATIENTS WITH ACTIVE EOSINOPHILIC ESOPHAGITIS: A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 TRIAL. Program No. 20. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.