P2226 - Dupilumab Improves Multiple Histopathologic Endpoints in Children With Eosinophilic Esophagitis: 52-Week Results From the Phase 3 EoE KIDS Trial

Award: Presidential Poster Award

Margaret H. Collins, MD¹, Marc E. Rothenberg, MD, PhD¹, Diana Lerner, MD², Robert D. Pesek, MD³, Navneet Virk Hundal, MD⁴, Ruiqi Liu, PhD⁵, Jennifer Maloney, MD⁵, Raolat M. Abdulai, MD, MSc⁶, Margee Louisias, MD, MPH⁶, Allen Radin, MD^5
1Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, CIncinnati, OH; ²Medical College of Wisconsin, Milwaukee, WI; ³University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR; ⁴Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA; ⁵Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁶Sanofi, Bridgewater, NJ

Introduction: Eosinophilic esophagitis (EoE) is a chronic, progressive disease, in which type 2 inflammation drives pathologic changes in esophageal tissue. Pathologic disease activity and severity can be assessed using peak intraepithelial eosinophil count (PEC). Additionally, the EoE Histologic Scoring System (EoE-HSS) is a validated measure scoring severity of changes (grade) and extent of pathology (stage) of 8 components. Dupilumab, a fully human monoclonal antibody that blocks key drivers of type 2 inflammation, interleukin (IL)-4 and IL-13, is approved in the USA for the treatment of patients with EoE aged ≥1 year, weighing ≥15 kg. This analysis assessed the impact of dupilumab vs placebo on PEC and EoE-HSS grade/stage scores, in pediatric patients aged 1 to < 12 years with active EoE in the phase 3 EoE KIDS trial (NCT04394351).

Methods: Part A was a 16-week (W), placebo-controlled study. Patients were randomized 2:2:1:1 to receive weight-tiered, higher-exposure (HE) or lower-exposure (LE) dupilumab, or placebo. In Part B, patients continued dupilumab per Part A, or switched from placebo to dupilumab (HE or LE), to W52. PEC eosinophils per high-power field (eos/hpf) and EoE-HSS grade/stage scores were assessed at W16 and W52.

Results: At W16, higher proportions of patients achieved ≤6 and < 15 eos/hpf with dupilumab HE vs placebo (67.6% vs 2.9% and 83.8% vs 2.9%, respectively). At W52, effects were maintained with continued dupilumab, and increased vs W16 in patients switching to dupilumab HE from placebo. Dupilumab HE also improved EoE-HSS grade and stage scores vs placebo at W16 (least squares mean difference vs placebo [95% confidence interval] -0.90 [-1.03, -0.77] and -0.88 [-1.01, -0.76], respectively). Improvements were maintained at W52. Similar improvements were observed in patients switching from placebo to dupilumab HE for most EoE-HSS components (Table). The safety profile of dupilumab was consistent with the overall known safety profile.

Discussion: Dupilumab treatment for 52 weeks improved PEC and the severity/extent of pathologic changes measured by EoE-HSS grade/stage scores. Similar improvements occurred in patients switching from placebo to dupilumab at W16. Dupilumab HE had a broad effect on pathologic abnormalities in the esophagus that was sustained to W52.


Disclosures:


Margaret H. Collins, MD¹, Marc E. Rothenberg, MD, PhD¹, Diana Lerner, MD², Robert D. Pesek, MD³, Navneet Virk Hundal, MD⁴, Ruiqi Liu, PhD⁵, Jennifer Maloney, MD⁵, Raolat M. Abdulai, MD, MSc⁶, Margee Louisias, MD, MPH⁶, Allen Radin, MD⁵. P2226 - Dupilumab Improves Multiple Histopathologic Endpoints in Children With Eosinophilic Esophagitis: 52-Week Results From the Phase 3 EoE KIDS Trial, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.