Pediatric Patients with Eosinophilic Esophagitis Administered Dupixent Achieve Significant Improvements Across Multiple Disease Measures

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Phase III trial data published by The New England Journal of Medicine (NEJM) show the efficacy of Dupixent (dupilumab) treating eosinophilic esophagitis (EoE) in children from one to 11 years of age. Investigators found that a greater proportion of children administered a weight-tiered higher dose of Dupixent achieved a significant improvement across multiple key disease measures for EoE compared to placebo at week 16.^1,2

“The NEJM publication of these Phase III [Dupixent] results is a testament to the importance of these data and potential for [Dupixent] to change the standard of care for many young children living with [EoE]. These children commonly experience feeding difficulties, food refusal and failure to thrive during a critical time of their growth and development,” principal trial investigator Mirna Chehade, MD, MPH, Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, said in a press release. “These data showed weight-tiered higher dose [Dupixent] significantly improved key [EoE] histologic, endoscopic, and cellular measures in children as young as 1 year old with sustained results for up to one year. These results reinforce the positive results seen in older patients with [EoE] and strengthen our understanding of IL4 and IL13 as key drivers of the type 2 inflammation underlying this disease.”¹

In January 2024, the FDA approved an expanded indication for Dupixent to treat EoE in patients aged one to 11 years weighing at least 33 lbs. The approval made Dupixent the first and only FDA-approved medication for EoE specifically in this patient population.³

The FDA approved the drug in May 2022 to treat EoE in patients aged 12 years and older, weighing at least 88 lbs. Dupixent, an interleukin-4 receptor alpha antagonist, is also indicated to treat adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable; asthma; chronic rhinosinusitis with nasal polyposis; and prurigo nodularis.

EoE is a chronic, progressive condition thought to be responsible for causing damage to the esophagus, severely affecting a patient’s ability to eat. Additional symptoms of the disease include heartburn, vomiting, abdominal discomfort, trouble swallowing, food refusal, and failure to thrive. Approximately 21,000 children in the United States under 12 years of age are currently being administered unapproved therapies for EoE.³

The randomized, double-blind, placebo-controlled Phase III EoE KIDS trial (NCT04394351) included separate parts that analyzed the safety and efficacy of Dupixent in patients under 12 years of age. Investigators enrolled patients aged one to 11 years with active EoE who were unable to achieve a response to proton-pump inhibitor therapies.

Patients were randomly assigned in a 2:2:1:1 ratio to 16 weeks of a higher-exposure or lower-exposure subcutaneous Dupixent regimen or to placebo for Part A of the trial. At the end of Part A, those eligible in each Dupixent cohort continued on their regimen and those in the placebo cohorts were assigned to higher-exposure or lower-exposure Dupixent for 36 weeks for Part B of the trial.

Through each level of exposure, patients received Dupixent in one of four doses tiered by their baseline body weight. The trial’s primary endpoint was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16, with key secondary endpoints evaluated hierarchically.

Investigators observed histologic remission in 25 of the 37 patients (68%) in the Part A higher-exposure cohort, in 18 of the 31 patients (58%) in the lower-exposure cohort, and in one of the 34 patients (3%) in the placebo cohort (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]).²

Patients in the higher-exposure Dupixent cohort achieved significant improvements in histologic, endoscopic, and transcriptomic measures compared to placebo. Investigators noted similar improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 and between baseline and week 16 among patients administered Dupixent in Part A.

Notably in Part A, incidence of COVID-19, nausea, injection site pain, and headache was at least 10 percentage points higher in either dose of the Dupixent cohort compared to the placebo cohort. Three patients in Part A of the Dupixent cohort reported serious adverse events (AEs) and six patients reported AEs overall throughout Part B.

“[Dupixent] resulted in histologic remission in a significantly higher percentage of children with [EoE] than placebo,” the study authors concluded. “The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo.”²

References

1. Dupixent positive phase 3 data in children one to 11 years of age with eosinophilic esophagitis published in NEJM. News release. Sanofi. June 26, 2024. Accessed June 27, 2024. https://www.news.sanofi.us/2024-06-26-Dupixent-positive-phase-3-data-in-children-one-to-11-years-of-age-with-eosinophilic-esophagitis-published-in-NEJM

2. Chehade M, et al. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. Published June 26, 2024. N Engl J Med 2024;390:2239-2251. DOI: 10.1056/NEJMoa2312282. Vol. 390 No. 24

3. Dupixent (dupilumab) FDA approved as first and only treatment indicated for children aged 1 year and older with eosinophilic esophagitis (EoE). Regeneron. News release. January 25, 2024. Accessed June 27, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-fda-approved-first-and-only-treatment