Phase 3 study follows recent approval of the drug for the same condition in individuals aged 12 years and older who weight at least 40 kg.
Regeneron Pharmaceuticals Inc and Sanofi announced that the phase 3 trial assessing dupilumab (Dupixent) for use in children aged 1 to 11 years with eosinophilic esophagitis (EoE) met its primary endpoint of histological disease remission at 16 weeks with both higher- and lower-dose weight-tiered regimens.
There is no approved treatment for individuals with EoE under aged 12 years.
“Dupixent is the first medicine to alleviate key signs of [EoE] in children as young as 1 year of age in a phase 3 trial. The efficacy of Dupixent demonstrates that in this age group, as in adults, IL-4 and IL-13 are key drivers of the type 2 inflammation underlying this debilitating disease," George Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, said in a statement.
“The positive results from this phase 3 pediatric trial show [dupilumab] has the potential to improve signs of [EoE] and support healthy weight gain in children from their first birthday,” he said.
In the trial, investigators randomized 102 individuals, aged 1 to 11 years, to receive dupilumab, in either a higher or lower dose based on their weight, or the placebo. At 16 weeks, approximately 68% of children on the higher dose and 58% of individuals on the lower dose achieved the primary endpoint of significant histological disease remission compared with 3% of individuals on the placebo.
Additionally, children receiving the higher dose of dupilumab experienced an 86% reduction of peak esophageal intraepithelial eosinophil count from baseline to 16 weeks compared with 21% increase on the placebo.
There was a 0.88 and 0.84 reduction from baseline to week 16 in disease severity and extent, respectively, measured at the microscopic level in biopsy specimens compared with 0.02 and 0.05 increases, respectively, for the placebo.
Furthermore, there was a 3.5-point reduction in abnormal endoscopic findings from baseline to 16 weeks compared with a 0.3-point increase for the placebo.
There was a numerical improvement in the proportion of days children experienced symptoms of EoE from the baseline, which was reported by caregivers, compared with the placebo, though the improvement was not statistically significant.
Investigators used the Pediatric EOE signs/symptoms questionnaire (PESQ-C), a novel endpoint developed by Regeneron and Sanofi, that was used for the first time during this trial. It was designed to assess the symptoms children experience through their caregivers.
As part of a prespecified exploratory analysis, a 3.09 percentile increase in body weight for age percentile from baseline compared with a 0.29 for the placebo.
The safety profile was generally consistent with the known safety profile for dupilumab in its approved EoE indication for children who are aged 12 years or older and weigh at least 40 kg.
The trial also met the anatomic, cellular, and histological secondary endpoints for the lower-dose group, and they were all comparable with the higher dosage and nominally significant.
The companies plan to share more detailed results at an upcoming medical meeting, including additional data for the endpoints in the lower-dose arm.
In May 2022, the FDA approved dupilumab at the 300-mg strength to treat individuals with EoE aged 12 years and older weighing at least 40 kg, after it was granted priority review by the FDA.
Dupixent (dupilumab) phase 3 trial shows positive results in children 1 to 11 years of age with eosinophilic esophagitis. Regeneron. News release. July 14, 2022. Accessed July 14, 2022. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-phase-3-trial-shows-positive-results