Late-breaking positive results from a phase 3 trial have shown that children with eosinophilic esophagitis (EoE) given a higher dose of Dupixent showed histological disease remission and signs of weight gain.
At week 16, 68% of children aged one to 11 years with active EoE on the higher dose displayed the positive results during the first and only phase 3 trial evaluating the investigational use of Dupixent (dupilumab). There are currently no approved treatments specifically indicated for children under 12 years of age with the condition.
The data will be submitted to regulatory authorities around the world, starting with the U.S. Food and Drug Administration (FDA) in 2023. In May 2022, Dupixent 300 mg weekly was approved by the FDA to treat EoE in people aged 12 years and older, weighing at least 40 kg.
Disease remission
Mirna Chehade, of Mount Sinai center for eosinophilic disorders, said: “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.
“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.”
Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
Significant improvements
It led to significant improvements in the primary efficacy measure for higher and lower dose groups at 16 weeks in the randomized, placebo-controlled phase 3 trial. Among children treated with Dupixent, 68% of children on higher dose and 58% of patients on lower dose achieved the primary endpoint of significant histological disease remission, compared to 3% for placebo.
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. Symptomatically, higher dose Dupixent led to a numerical improvement in the proportion of days children experienced disease symptoms from baseline as reported by their caregivers compared to placebo, though not statistically significant.
Additionally, a prespecified exploratory analysis was presented which found higher dose Dupixent led to a 3.09 percentile increase in body weight for age percentile from baseline, compared to 0.29 for placebo.
Adverse events
Safety results were generally consistent with the known safety profile of Dupixent in its approved EoE indication for children and adults aged 12 years and older who weigh at least 40 kg. For the 16-week treatment period, the overall rates of adverse events (AEs) were 79%, lower dose for Dupixent and 91% for placebo.
AEs most commonly observed with Dupixent (5% or less) compared to placebo included COVID-19 though all cases were mild or moderate and did not lead to study discontinuation, rash, headache, viral gastroenteritis, diarrhea and nausea. Rates of treatment discontinuation due to AEs prior to week 16 were 0% for Dupixent and 6% for placebo.
The potential use of Dupixent in children with EoE aged 1 to 11 years is currently under clinical development, and the safety and efficacy have not been evaluated by any regulatory authority.
EoE is a chronic inflammatory disease that damages the esophagus and prevents it from working properly. The results seen with Dupixent in adults and children with EoE demonstrate that interlukin-4 and interlukin-13 are key and central drivers of the type 2 inflammation underlying this disease.