11 - Dupilumab Improves Clinical, Symptomatic, Histologic, and Endoscopic Aspects of EoE up to 24 Weeks: Pooled Results From Parts A and B of Phase 3 LIBERTY-EoE-TREET

Award: Outstanding Research Award in the Esophagus Category

Evan Dellon, MD, MPH¹, Marc Rothenberg, MD, PhD², Albert Bredenoord, MD, PhD³, Alfredo Lucendo, MD⁴, Ikuo Hirano, MD, PhD⁵, Xian Sun, PhD⁶, Kiran Patel, PhD⁷, Bethany Beazley, PhD^6
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; ³Amsterdam University Medical Center, Amsterdam, Utrecht, Netherlands; ⁴Hospital General de Tomelloso, Tomelloso, Madrid, Spain; ⁵Northwestern University Feinberg School of Medicine, Chicago, IL; ⁶Regeneron Pharmaceuticals, Tarrytown, NY; ⁷Sanofi, Tarrytown, NY

Introduction: Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of the esophagus. Current treatment offers suboptimal long-term disease control. Dupilumab, a fully human mAb, blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 inflammation. In a phase 2 proof-of-concept study, dupilumab significantly improved histological and clinical outcomes of EoE with an acceptable safety profile. Here we report the pooled results from Parts A and B of a three-part, randomized, placebo-controlled phase 3 study (NCT03633617) which evaluated the efficacy and safety of weekly dupilumab 300 mg vs placebo in adult and adolescent patients with EoE for 24 weeks.

Methods: Patients were randomized 1:1 to weekly dupilumab (N=122) or placebo (N=118). Endpoints (all at Week 24): proportion of patients achieving peak eosinophil count ≤6/high-power field (hpf); absolute and % change in Dysphagia Symptom Questionnaire (DSQ) score; % change in peak eosinophil count; absolute change in Histologic Scoring System (HSS) grade and stage scores and Endoscopic Reference Score (EREFS); proportion of patients achieving peak eosinophil count < 15/hpf. Binary endpoints were assessed using the Cochran-Mantel-Haenszel (CMH) test. Continuous endpoints were analyzed using an analysis of covariance (ANCOVA) model. Nominal P-values are reported for this post-hoc analysis.

Results: Baseline characteristics were comparable between treatment groups. More patients treated with dupilumab versus placebo achieved peak eosinophil count ≤6/hpf (59.0% vs 5.9%; P< 0.0001). Dupilumab vs placebo had greater absolute (LS mean –23.2 vs –12.7; LS mean difference [95% CI] –10.5 [–14.5, –6.6]; P< 0.0001) and % (–65.5% vs –38.3%; –27.3 [–38.2, –16.2]; P< 0.0001) change in DSQ. Dupilumab vs placebo had a greater % change in peak eosinophil count (–80.1 vs 1.5; –81.7 [–96.2, –67.1]); proportion of patients achieving < 15 eos/hpf (77.0% vs 7.6%); change in HSS grade (–0.82 vs –0.1; –0.71 [–0.81, –0.62]) and stage (–0.79 vs –0.09; –0.70 [–0.79, –0.61]) scores; and change in EREFS score (–3.95 vs –0.41; –3.54 [–4.27, –2.81]); all P< 0.0001. Dupilumab was generally well tolerated. The most common TEAEs for dupilumab/placebo were injection-site reactions (37.5/33.3%).

Discussion: Dupilumab improved clinical, symptomatic, histologic, and endoscopic aspects of EoE and was well tolerated.



Disclosures:


Evan Dellon, MD, MPH¹, Marc Rothenberg, MD, PhD², Albert Bredenoord, MD, PhD³, Alfredo Lucendo, MD⁴, Ikuo Hirano, MD, PhD⁵, Xian Sun, PhD⁶, Kiran Patel, PhD⁷, Bethany Beazley, PhD⁶, 11, Dupilumab Improves Clinical, Symptomatic, Histologic, and Endoscopic Aspects of EoE up to 24 Weeks: Pooled Results From Parts A and B of Phase 3 LIBERTY-EoE-TREET, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.