Dupixent phase III trial shows positive results in children 1 to 11 years of age with eosinophilic esophagitis
Regeneron Pharmaceuticals, Inc. and Sanofi announced that a Phase III trial assessing the investigational use of Dupixent (dupilumab) 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 are no approved treatments for children with EoE under 12 years of age.
"Dupixent is the first medicine to alleviate key signs of eosinophilic esophagitis in children as young as 1 year of age in a Phase III 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," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. "Eosinophilic esophagitis can turn the basic and life-sustaining act of eating into a painful experience at a point in children's lives when proper nutrition and achieving a healthy weight is critical to ensuring they grow and thrive. The positive results from this Phase III pediatric trial show Dupixent has the potential to improve signs of eosinophilic esophagitis and support healthy weight gain in children from their first birthday."
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 IL-4 and IL-13 are key drivers of the type 2 inflammation underlying this disease. In children, common symptoms of eosinophilic esophagitis include acid reflux, vomiting, abdominal discomfort, trouble swallowing, and a failure to thrive. These symptoms can impact growth and development, and can cause food-related fear and anxiety which can persist through adulthood. Diet adjustments, which oftentimes include the elimination of many foods, is the standard treatment for EoE, as well as the use of treatments not approved for the disease. These include proton pump inhibitors, swallowed topical corticosteroids, or in severe cases, a feeding tube, which may be used to ensure proper caloric intake and weight gain. Of the approximately 21,000 children under the age of 12 in the U.S. currently being treated for EoE, about 9,000 do not satisfactorily respond to the unapproved therapies they have been treated with and potentially require advanced therapy.
In the Phase III trial, 102 children aged 1 to 11 were randomized to receive Dupixent, in either a higher dose (n=37) or lower dose (n=31) regimen based on body weight, or placebo (n=34). At 16 weeks, 68% of children on higher dose and 58% of patients on lower dose Dupixent achieved the primary endpoint of significant histological disease remission (peak esophageal intraepithelial eosinophil count of ?6 eosinophils [eos]/high power field [hpf]) compared to 3% of children on placebo (p<0.0001 for both).
Additionally, children receiving higher dose Dupixent experienced the following changes at week 16: i. 86% reduction in peak esophageal intraepithelial eosinophil count from baseline compared to a 21% increase for placebo (p<0.0001). ii. 0.88 and 0.84 reduction from baseline in disease severity and extent, respectively, as measured at the microscopic level in biopsy specimens compared to a 0.02 and 0.05 increase for placebo (both p><0.0001). iii. 3.5-point reduction in abnormal endoscopic findings from baseline compared to a 0.3-point increase for placebo (p><0.0001). iv. a numerical improvement in the proportion of days children experienced symptoms of eoe from baseline, as reported by caregivers (pediatric eoe signs symptoms questionnaire [pesq-c]), compared to placebo, though not statistically significant. the pesq-c is a novel endpoint developed by regeneron and sanofi used for the first time in this trial, designed to assess symptoms in young children through their caregivers (as signs), as children may have difficulty verbalizing their symptoms themselves. v. as part of a prespecified exploratory analysis, a 3.09 percentile increase in body weight for age percentile from baseline compared to 0.29 for placebo. vi. histological, anatomic and cellular secondary endpoints were also analyzed for the lower dose group, with all being nominally significant and generally comparable with the higher dose. more detailed results will be shared at an upcoming medical meeting, including additional data for the endpoints in the lower dose group.
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, overall rates of adverse events (AEs) were 79% for Dupixent and 91% for placebo. AEs more commonly ( greater than 5%) observed with Dupixent compared to placebo included COVID-19 (21% Dupixent, 0% placebo; all cases were mild or moderate and did not lead to study discontinuation), rash (9% Dupixent, 6% placebo), headache (8% Dupixent, 3% placebo), viral gastroenteritis (6% Dupixent, 3% placebo), diarrhea (6% Dupixent, 3% placebo) and nausea (6% Dupixent, 0% placebo). Rates of treatment discontinuation due to AEs prior to week 16 were 0% for Dupixent and 6% for placebo.
In May 2022, the FDAapproved Dupixent 300 mg weekly to treat patients with EoE aged 12 years and older and weighing at least 40 kg after granting the medicine Priority Review.
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