FDA Accepts Priority Review Application for Dupilumab for Pediatric Eosinophilic Esophagitis

Mirna Chehade, MD, MPH

Credit: Mount Sinai

Regeneron Pharmaceuticals announced the US Food and Drug Administration (FDA) has accepted their supplemental Biologics License Application for dupilumab (Dupixent) for priority review in the treatment of children aged 1-11 years with eosinophilic esophagitis.¹

Announced on September 26, 2023, the application is supported by data from the phase 3 EoE KIDS trial, which showed 68% of patients on a higher dose of dupilumab and 58% of patients on a lower dose achieved significant histological disease remission, and the target action date for the FDA decision is January 31, 2024.²

"Eosinophilic esophagitis impacts a child's fundamental ability to eat, which is especially critical in early childhood when healthy weight gain is vital to long-term health and development," said principal investigator Mirna Chehade, MD, MPH, of the Center for Eosinophilic Disorders and Icahn School of Medicine at Mount Sinai, at the time results of the trial were presented in October 2022.² "These Phase 3 data support the potential of dupilumab to reduce esophageal damage – caused in part by underlying type 2 inflammation – and showed histological disease remission and signs of weight gain impacting the growth percentile for those children on higher dose Dupixent."

A fully human monoclonal antibody, dupilumab inhibits the signaling of interleukin-4 and interleukin-13 pathways and has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 trials.¹ On May 20, 2022, the FDA approved dupilumab 300 mg weekly to treat patients with eosinophilic esophagitis aged 12 years and older weighing at least 40 kg, making it the first and only medicine specifically indicated to treat eosinophilic esophagitis in the United States.⁴

A randomized, double-blind, placebo-controlled study, EoE KIDS evaluated the safety and efficacy of dupilumab in pediatric patients with eosinophilic esophagitis. The trial's primary endpoint was the proportion of patients achieving histological disease remission at 16 weeks for tiered dosing regimens based on body weight compared to placebo. At the conclusion of the 16-week treatment period, patients were enrolled in an additional 36-week active treatment extension period.²

To be included in the study, participants were required to be aged 1-11 years, have a documented diagnosis of eosinophilic esophagitis, and have baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration.³

In total, 102 participants were enrolled in the study and received placebo or dupilumab subcutaneously at either a higher dose or lower dose regimen based on their weight over a 16-week period. The primary outcome of interest was histological disease remission, defined for the purpose of analysis as peak esophageal intraepithelial eosinophil count of ≤6 eosinophils/high power field. Secondary endpoints included abnormal endoscopic findings and changes in caregiver-reported symptoms.³

Results of the trial, which were presented at United European Gastroenterology Week 2022, indicated 68% of patients on a higher dose and 58% of patients on a lower dose achieved significant histological disease remission compared to 3% for placebo (both P < .0001). Of note, children on the higher dose regimen also experienced significant improvements in abnormal endoscopic findings of their esophagus, with a reduction of 3.5 points compared to an increase of 0.3 points for placebo (P < .0001).²

Safety results were generally consistent with the known safety profile of dupilumab in its approved eosinophilic esophagitis indication for children and adults aged 12 years and older who weigh at least 40 kg. On May 20, 2022, the FDA approved dupilumab 300 mg weekly to treat patients with eosinophilic esophagitis aged 12 years and older weighing at least 40 kg, making it the first and only medicine specifically indicated to treat eosinophilic esophagitis in the United States.⁴

For the 16-week treatment period in EoE KIDS, the overall rates of adverse events were 79% for dupilumab and 91% for placebo. Adverse events most commonly observed with dupilumab compared to placebo included COVID-19, rash, headache, viral gastroenteritis, diarrhea, and nausea. Rates of treatment discontinuation due to adverse events prior to week 16 were 0% for dupilumab and 6% for placebo.²

References:

1. Regeneron. DUPIXENT® (DUPILUMAB) SBLA FOR TREATMENT OF EOSINOPHILIC ESOPHAGITIS (EOE) IN CHILDREN AGED 1 TO 11 ACCEPTED FOR FDA PRIORITY REVIEW. Press Releases. September 26, 2023. Accessed September 26, 2023. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-sbla-treatment-eosinophilic-esophagitis-eoe
2. Regeneron. DUPIXENT® (DUPILUMAB) LATE-BREAKING PHASE 3 DATA PRESENTED AT UEG WEEK 2022 SHOWED SIGNIFICANT HISTOLOGICAL REMISSION OF EOSINOPHILIC ESOPHAGITIS (EOE) IN CHILDREN 1 TO 11 YEARS OLD. Press Releases. October 11, 2022. Accessed September 26, 2023. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-late-breaking-phase-3-data-presented-ueg
3. Clinicaltrials.gov. Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE) (EoE KIDS). June 5, 2023. Accessed September 26, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04394351
4. Regeneron. FDA APPROVES DUPIXENT® (DUPILUMAB) AS FIRST TREATMENT FOR ADULTS AND CHILDREN AGED 12 AND OLDER WITH EOSINOPHILIC ESOPHAGITIS. Press Releases. May 20, 2022. Accessed September 26, 2023. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-dupixentr-dupilumab-first-treatment-adults-and