LB3 - (LATE-BREAKING ABSTRACT) A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis: Results From Part A
Evan S. Dellon, MD, MPH, FACG1, Marc E. Rothenberg2, Margaret H. Collins2, Ikuo Hirano3, Mirna Chehade4, Albert J Bredenoord5, Alfredo J. Lucendo6, Jonathan M. Spergel7, Qiong Zhao8, Jennifer D. Hamilton8, Bethany Beazley8, Isabelle Guillemin9, Siddhesh Kamat8, Leda Mannent9, Marcella Ruddy8, Elizabeth Laws10, Bolanle Akinlade8, Nikhil Amin8, Allen Radin8, Brad Shumel8, Jennifer Maloney8; 1University of North Carolina School of Medicine, Chapel Hill, NC, 2Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, 3Northwestern University Feinberg School of Medicine, Chicago, IL, 4Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, 5Amsterdam University Medical Center, Amsterdam, Netherlands, 6Hospital General de Tomelloso, Tomelloso, Spain, 7Children's Hospital of Philadelphia, PA, 8Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 9Sanofi, Chilly-Mazarin, France, 10Sanofi, Bridgewater, NJ
Introduction: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease of the esophagus that substantially impairs quality of life. Response to current standard of care is suboptimal. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation in EoE. In a phase 2 proof-of-concept study, dupilumab improved histological and clinical outcomes of EoE with an acceptable safety profile. Part A of a three-part, randomized, placebo-controlled phase 3 study (NCT03633617) evaluated the efficacy and safety of weekly dupilumab 300 mg vs placebo in adult and adolescent patients with EoE for 24 weeks. Methods: In total, 81 patients were randomized 1:1 to receive dupilumab (42 patients) or placebo (39 patients) for a 24-week treatment period. Co-primary endpoints were the proportion of patients achieving a peak esophageal intraepithelial eosinophil (eos) count of < 6 eos/high-power field (hpf), and the absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score at Week 24. Secondary endpoints included absolute change from baseline in EoE histologic scoring system (EoEHSS) mean grade and stage scores, absolute change in total EoE Endoscopic Reference Score (EREFS), and proportion of patients achieving a peak eos count of < 15 eos/hpf. Results: Baseline characteristics were comparable in the two treatment groups. A significantly greater proportion of patients receiving dupilumab vs placebo achieved peak eos counts of < 6 eos/hpf (59.5% vs 5.1%, P < 0.001; Table) and < 15 eos/hpf (64.3% vs 7.7%, P < 0.001). Compared with placebo, dupilumab-treated patients had a significantly greater change from baseline in DSQ score (LS mean difference: −12.32 [95% CI −19.11 to −5.54], P < 0.001); EoEHSS mean grade (LS mean difference: −0.76 [95% CI −0.91 to −0.61], P < 0.001); and stage scores (LS mean difference: −0.74 [95% CI −0.88 to −0.60], P < 0.001); and total EREFS (LS mean difference: −2.9 [95% CI −3.91 to −1.84], P < 0.001). Dupilumab was generally well tolerated; the most common treatment-emergent adverse events for dupilumab vs placebo were injection-site reactions (16.7% vs 10.3%) and nasopharyngitis (11.9% vs 10.3%). Discussion: In this phase 3 study, weekly dupilumab demonstrated significant and clinically meaningful improvements in histologic, symptomatic, and endoscopic measures of EoE, and was well tolerated.
Acknowledgments and funding sources - Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT03633617. Medical writing/editorial assistance provided Grace Manley, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
Summary of co-primary and secondary outcomes at Week 24 in Part A of the phase 3 EoE study
Disclosures: Dr. Dellon - Consultant: Abbott, Adare, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Biorasi, Calypso, Eli Lilly, EsoCap, Gossamer Bio, GlaxoSmithKline, Parexel, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Robarts, Salix, Shire/Takeda; research funding: Adare, Allakos, GlaxoSmithKline, Meritage, Miraca, Nutricia, Receptos/Celegene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire/Takeda; educational grant: Allakos, Banner, Holoclara. Dr. Rothenberg - Consultant: Allakos, AstraZeneca, Bristol Myers Squibb, ClostraBio, Pulm One, Spoon Guru; equity interest: ClostraBio, Pulm One, Spoon Guru; royalties from reslizumab: Teva Pharmaceuticals; royalties from PEESSv2: Mapi Research Trust; royalties: UpToDate; inventor of patents owned by Cincinnati Children’s Hospital. Dr. Collins - consultant: Allakos, Arena, AstraZeneca, Bristol Myers Squibb, Calypso, Esocap, GlaxoSmithKline, Regeneron Pharmaceuticals, Inc., Shire; research funding: Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire. Dr. Hirano - consultant: Adare, Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire; research funding: Meritage, Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals, Inc., Shire. Dr. Chehade - consultant: Adare, Allakos, Astra Zeneca, Nutricia, Regeneron Pharmaceuticals, Inc., Shire; research funding: Allakos, Regeneron Pharmaceuticals Inc., Shire; honoraria for lectures: Medscape, Nutricia. Dr. Bredenoord – consultant: Arena, AstraZeneca, Calypso, EsoCap, Falk, Gossamer Bio, Medtronic, Laborie, RB, Regeneron, Robarts; research funding: Bayer, Nutricia, SST; equity interest: SST. Dr. Lucendo – Consultant: EsoCap, Dr. Falk Pharma; Research funding: Dr. Falk Pharma, Regeneron Pharmaceuticals. Dr. Spergel – Consultant: Regeneron, Shire, Takeda, Allakos, DBV Technology, Novartis; Grant Support: Regeneron, DBV Technology. Q Zhao, JD Hamilton, B Beazley, S Kamat, M Ruddy, B Akinlade, N Amin, A Radin, B Shumel, J Maloney: Regeneron Pharmaceuticals, Inc. – Employees and Shareholders. I Guillemin: Sanofi – Prior employee, may hold stock and/or stock options in the company L Mannent, E Laws: Sanofi – Employees, may hold stock and/or stock options in the company.