Earlier this year, the United States (US) Food and Drug Administration (FDA) expanded the approval of dupilumab to include the treatment of eosinophilic esophagitis (EoE) in pediatric patients aged ≥1 year weighing at least 15 kg.¹ This decision was based on the significant improvements in various key disease measures of EoE with dupilumab compared to placebo in pediatric patients observed in the phase 3 EoE KIDS clinical trial.²

EoE is a chronic, progressive esophageal disease characterized by eosinophilic infiltration and type 2 esophageal inflammation, leading to symptoms such as dysphagia, food impaction, and strictures.^2-4 In children, EoE can also cause failure to thrive, feeding difficulties, vomiting, reduced quality of life, and an increased risk of esophageal fibrosis if left untreated.^2-4 The prevalence of EoE has been steadily increasing, making it one of the major causes of upper gastrointestinal morbidity in the last two decades.^4,5

Previously, dupilumab had demonstrated favorable efficacy and safety of dupilumab in patients aged ≥12 years and weighing ≥40kg with EoE in the phase 3 LIBERTY EoE TREET trial, leading to its initial approval for the treatment of EoE in adults and adolescents.^2,3 However, the efficacy and safety of dupilumab in young children under 12 years of age had not been established until the EoE KIDS trial.² The new expanded approval now allows for the use of dupilumab in the younger pediatric population in the US.¹

The EoE KIDS was a phase 3 trial conducted in three parts (parts A, B, and C) to evaluate the efficacy and safety of dupilumab in children with EoE.² Part A was the randomized, double-blinded, placebo-controlled phase.² The study included patients between 1 and 11 years of age, who had active EoE, a clinical history of EoE-related symptoms, and were unresponsive to treatment with proton-pump inhibitors (PPIs).² A total of 102 eligible patients were enrolled and randomized into 3 arms to receive 16 weeks of higher-exposure (HE) dupilumab (n=37), lower-exposure (LE) dupilumab (n=31), or placebo (n=34).² Part B was the extended active treatment phase where after part A (16 weeks), patients in the HE and LE dupilumab arms continued their assigned dupilumab regimen while those in the placebo arm were assigned to receive HE or LE dupilumab for another 36 weeks.² Part C, the 108-week open-label extension phase, is still ongoing.² Dupilumab was administered subcutaneously in 1 of 4 doses tiered according to baseline body weight.²

The primary endpoint in part A was the proportion of patients who achieved histologic remission, defined as a peak esophageal intraepithelial eosinophil count of ≤6 at week 16.² At week 16, the proportion of patients who achieved histologic remission was significantly higher in the HE dupilumab arm compared to the placebo arm (68% vs. 3%; difference of 65% points, 95% CI: 48-81; p<0.001).² Similarly, the proportion of patients achieving histologic remission was significantly higher in the LE dupilumab arm compared to placebo (58% vs. 3%; difference of 55% points, 95% CI: 37-73; p<0.001).² Continuous dupilumab regimen, at either dose, showed consistent improvement in histologic and endoscopic measures throughout 52 weeks.² Similar changes in these measures were seen in patients who switched from placebo to dupilumab regimens in part B as well.²

Secondary endpoints included measures of histologic, transcriptomic, and endoscopic improvement from baseline, analyzed in a hierarchical testing approach.² The HE dupilumab regimen resulted in significant improvements compared to placebo in all secondary endpoints at week 16, including peak esophageal intraepithelial eosinophil count, EoE histology scoring system (EoE-HSS) grade and stage scores, total Eosinophilic Esophagitis Reference Score (EREFS), gene signatures of type 2 inflammation, and gene signatures of eosinophilic esophagitis diagnostic panel (EDP) (p<0.001 for all).²

In terms of safety, most adverse events (AEs) assessed by the investigator over 52 weeks were mild or moderate.² Patients who received dupilumab in part A had a ≥10% higher incidence rate of coronavirus disease 2019, nausea, injection-site pain, and headache compared to placebo.² Overall, dupilumab demonstrated a tolerable safety profile in pediatrics, similar to that observed in adults and adolescents.²

In summary, histologic remission occurred in a significantly greater proportion of pediatric patients aged 1-11 years with weight-tiered dupilumab treatment regimens compared to placebo (68% in the HE group and 58% in the LE group vs. 3% in placebo, p<0.001 for both).² Dupilumab also led to significant improvements in histologic, endoscopic, and transcriptomic outcome measures, with a tolerable safety profile.² Based on these results, the FDA approved the use of dupilumab for the treatment of eosinophilic esophagitis in adult and pediatric patients aged ≥1 year.¹