Dupixent® Phase 3 Success for Children 1-11 with Eosinophilic Esophagitis Published in NEJM

Regeneron Pharmaceuticals and Sanofi have announced the publication of positive results from a Phase 3 trial of Dupixent® (dupilumab) in children aged 1 to 11 years with eosinophilic esophagitis (EoE) in the New England Journal of Medicine (NEJM). This marks a significant step forward, as the trial demonstrated that a higher proportion of children receiving a weight-tiered higher dose of Dupixent showed substantial improvements in key measures of the disease compared to those receiving a placebo by week 16. These results formed the basis for the U.S. FDA's Priority Review and subsequent approval of Dupixent for children in this age group weighing at least 15 kg. The European Medicines Agency is also currently reviewing the data for this age group.

EoE is a chronic, progressive disease linked to type 2 inflammation, which damages the esophagus and impairs its function. Symptoms often overlap with other conditions, making diagnosis challenging and often delayed. EoE can significantly affect a child's ability to eat, leading to abdominal pain, difficulty swallowing, heartburn, vomiting, and failure to thrive. Long-term management is crucial to mitigate complications and prevent disease progression.

Dr. Mirna Chehade, the principal investigator of the trial, emphasized the importance of these findings. She noted that children with EoE often struggle with feeding difficulties and failure to thrive, which can hinder their growth and development. The trial showed that weight-tiered higher doses of Dupixent significantly improved histologic, endoscopic, and cellular measures of EoE in children as young as one year old, with sustained benefits for up to one year. These findings align with positive results previously observed in older patients with EoE, reinforcing the role of IL-4 and IL-13 as key drivers of type 2 inflammation in this disease.

The trial had two parts: Part A and Part B. In Part A, a significantly greater proportion of children receiving higher doses of Dupixent achieved histologic remission by week 16 compared to the placebo group. These children also experienced sustained improvements in disease severity, as assessed by endoscopic measures, for up to one year. Children receiving the lower dose of Dupixent showed improvements that were either comparable or slightly lower than those in the higher dose group. Additionally, Dupixent led to a numerical improvement in body weight for age percentile by week 16, which was maintained at one year. This was evaluated as an exploratory endpoint in Part A and as a secondary endpoint in Part B.

The safety profile of Dupixent in the trial was consistent with its known safety profile in adolescents and adults with EoE. Common adverse events observed in the weight-based dosing regimen during Part A included COVID-19, nausea, injection site pain, and headache. Long-term safety results through Part B were similar to those observed in Part A, with one case of helminth infection reported with Dupixent.

For U.S. patients with EoE weighing at least 15 kg, the FDA-approved dosage of Dupixent is 200 mg or 300 mg every other week, or 300 mg weekly, depending on weight. Dr. Chehade has served as a paid consultant for Regeneron and Sanofi and has received research grant funding from Regeneron.

The Phase 3 trial was a randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of Dupixent in children aged 1 to 11 years with EoE. Part A included 102 patients and assessed Dupixent at a weight-tiered higher dose or lower dose regimen compared to placebo over 16 weeks. Part B was a 36-week extended active treatment period where eligible children from Part A continued their Dupixent regimen, while those in the placebo group switched to Dupixent. The primary endpoint was histologic remission at 16 weeks, with secondary endpoints assessing the severity of the disease through endoscopic and histopathologic measures, as well as clinical signs and symptoms of EoE. Body weight-for-age percentile change was also evaluated.

Dupixent, developed using Regeneron's VelocImmune® technology, is a fully human monoclonal antibody that inhibits the IL-4 and IL-13 pathways and is not an immunosuppressant. The drug has shown significant clinical benefits in reducing type 2 inflammation across various related diseases. Dupixent has received approvals in more than 60 countries for multiple indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, EoE, prurigo nodularis, and chronic spontaneous urticaria in different age populations. Over 850,000 patients worldwide are being treated with Dupixent.

Regeneron and Sanofi continue to investigate Dupixent in a range of diseases driven by type 2 inflammation or allergic processes, with several Phase 3 trials currently underway.