Positive results were announced from a phase 3 study evaluating the efficacy and safety of dupilumab in patients 1 to 11 years of age with eosinophilic esophagitis (EoE).
Dupilumab, an interleukin-4 receptor alpha antagonist, is currently marketed under the brand name Dupixent® and is indicated for the treatment of eosinophilic esophagitis in patients 12 years of age and older weighing at least 40kg; for the treatment of moderate to severe atopic dermatitis in patients 6 years of age and older; for maintenance treatment of severe asthma in patients 12 years of age and older; and for chronic rhinosinusitis with nasal polyps in patients 18 years of age and older.
The randomized, double-blind, placebo-controlled EoE KIDS study (ClinicalTrials.gov Identifier: NCT04394351) included 102 patients 1 to 11 years of age with active EoE based on histologic improvement meeting validated histologic criteria. Patients were randomly assigned to receive dupilumab, at either a higher dose (n=37) or lower dose (n=31) based on body weight, or placebo (n=34). The primary endpoint was histological disease remission, defined as the proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eosinophils [eos]/high power field [hpf]) at week 16.
Findings showed that 68% and 58% of patients treated with the higher and lower dose of dupilumab, respectively, achieved significant histological disease remission at week 16 compared with 3% of those who received placebo (P <.0001 for both). Moreover, patients treated with the higher dose of dupilumab achieved the following at week 16:
- A 86% reduction in peak esophageal intraepithelial eosinophil count from baseline vs a 21% increase for placebo (P <.0001).
- A 0.88 and 0.84 reduction from baseline in disease severity and extent, respectively, as measured at the microscopic level in biopsy specimens vs a 0.02 and 0.05 increase for placebo (both P <.0001).
- A 3.5-point reduction in abnormal endoscopic findings from baseline vs a 0.3-point increase for placebo (P <.0001).
The safety profile of dupilumab in patients 1 to 11 years of age was generally consistent with that seen in patients aged 12 years and older. Adverse events more commonly observed with dupilumab compared with placebo included COVID-19 (21% dupilumab, 0% placebo; all cases were mild or moderate), rash (9% dupilumab, 6% placebo), headache (8% dupilumab, 3% placebo), viral gastroenteritis (6% dupilumab, 3% placebo), diarrhea (6% dupilumab, 3% placebo), and nausea (6% dupilumab, 0% placebo).
“Dupixent is the first medicine to alleviate key signs of eosinophilic esophagitis in children as young as 1 year of age in a phase 3 trial,” said George D. Yancopoulos, MD, PhD, President and CSO at Regeneron, and a principal inventor of Dupixent. 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.”
Exploratory analysis also showed the dupilumab higher dose group had a 3.09 percentile increase in body weight for age percentile from baseline compared with 0.29 for placebo. Detailed study results will be shared at an upcoming medical meeting, including additional data for the endpoints in the lower dose group.
Dupixent® (dupilumab) phase 3 trial shows positive results in children 1 to 11 years of age with eosinophilic esophagitis. News release. Regeneron Pharmaceuticals, Inc. Accessed July 14, 2022. https://www.prnewswire.com/news-releases/dupixent-dupilumab-phase-3-trial-shows-positive-results-in-children-1-to-11-years-of-age-with-eosinophilic-esophagitis-301586407.html