In 2 different dose groups, the majority of patients with eosinophilic esophagitis aged 1 to 11 achieved histologic remission at week 16 compared with patients treated with placebo.
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Trial Name: Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE) (EoE KIDS)
ClinicalTrials.gov ID: NCT04394351
Sponsor: Regeneron Pharmaceuticals
Completion Date (Estimated): July 7, 2025
Positive phase 3 trial results (NCT04394351) for dupilumab (Dupixent; Sanofi, Regeneron) in children aged 1 to 11 years with eosinophilic esophagitis (EoE) were recently published in the New England Journal of Medicine. The results demonstrated that, compared to placebo, those who received a weight-tiered higher dose of dupilumab experienced significant improvements in key disease measures of EoE at week 16.1
Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways, and is not an immunosuppressant. Previously, the treatment showed clinical benefit and a decrease in type 2 inflammation in phase 3 trials. IL-4 and IL-13 are both key and central drivers of type 2 inflammation, which plays a significant role in multiple related—and often comorbid—diseases. Additionally, dupilumab is approved for indications in multiple conditions, such as asthma, EoE, atopic dermatitis, chronic rhinosinusitis with nasal polyposis, among others.1 Data from the current clinical trial, according to the investigators, were the basis for the FDA’s approval and priority review of dupilumab in pediatric patients with EoE aged 1 to 11 years who weigh at least 15 kg.1,2
“The NEJM publication of these phase 3 dupilumab results is a testament to the importance of these data and potential for dupilumab to change the standard of care for many young children with EoE. These children commonly experience feeding difficulties, food refusal, and failure to thrive during a critical time of their growth and development,” said principal trial investigator Mirna Chehade, MD, MPH, from the Mount Sinai Center for Eosinophilic Disorders and Ichan School of Medicine at Mount Sinai, New York, NY, in a news release.1
In the 2-part, double-blind, placebo-controlled, randomized phase 3 trial (NCT04394351), 102 patients aged 1 to 11 years with active EoE who did not respond to proton-pump inhibitors were randomly assigned to receive either higher-exposure or lower-exposure subcutaneous administrations of a dupilumab regimen or placebo. Part A consisted of randomization, and part B involved eligible patients in each of the 2 dupilumab exposure groups continuing the same regimen, and those in placebo groups assigned to either higher-exposure or lower-exposure dupilumab for a 36-week period. According to the investigators, dupilumab was administered in 1 of 4 doses at each level of exposure and according to the patients’ baseline body weight.3
The trial’s primary end point was histologic remission (peak esophageal intraepithelial eosinophil count: ≤6 per high-power field) at 16 weeks. Secondary end points consisted of assessments of endoscopic and histopathologic measures of disease severity, as well as clinical signs and symptoms of EoE, which were tested hierarchically.1,3
According to the findings, a greater proportion of children who received either a weight-tiered higher (25 of 37 patients; 68%) or lower dose (18 of 31 patients; 58%) regimen of dupilumab achieved histologic remission at week 16 during part A, compared with placebo (1 of 34 patients; 3%). Additionally, those who received the higher dose experienced significant improvements in disease severity, with improvements being sustained for up to 1 year. The patients who received the lower dose of dupilumab had also experienced improvements; however, these were either comparable or numerically lower than those shown in the higher dose group.1,3
The investigators note that safety results were generally consistent with the known safety profile of dupilumab in both adolescents and adults with EoE. The most common adverse events observed by those treated with dupilumab (in either dose group) were COVID-19 infection, nausea, injection site pain, and headache in part A. Additionally, the long-term safety profile of dupilumab in part B was similar to part A, with only 1 occurrence of helminth infection reported.1,3
“These data showed weight-tiered higher dose dupilumab significantly improved key EoE histologic, endoscopic and cellular measures in children as young as 1 year old with sustained results for up to 1 year. These results reinforce the positive results seen in older patients with EoE and strengthen our understanding of IL-4 and IL-13 as key drivers of the type 2 inflammation underlying this disease,” said Chehade in the news release.1
