Dupilumab confers remission of eosinophilic esophagitis in young children



Disclosures: Yancopoulos claims to have worked at Regeneron and to be the main inventor of dupilumab. Patel reports a job at Sanofi.

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According to the results of a phase 3 trial, children aged 1 to 11 years with eosinophilic esophagitis safely achieved histological remission of the disease after 16 weeks of treatment with the fully human monoclonal antibody dupilumab.

Dupilumab (Dupixent, Sanofi Genzyme/Regeneron) inhibits signaling of the IL-4 and IL-13 pathways responsible for type 2 inflammation. It is currently FDA-approved for the treatment of eosinophilic esophagitis in adults and children aged 12 and over.

The data comes from the press release.

“Eosinophilic esophagitis can turn the fundamental and vital act of eating into a painful experience at a time in children’s lives when good nutrition and achieving a healthy weight are essential for their growth and development. “, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, said in a press release from the company.

George D. Yancopoulos

“Positive results from this Phase 3 pediatric trial show that Dupixent has the potential to improve the signs of eosinophilic esophagitis and promote healthy weight gain in children as young as their first birthday,” said Yancopoulos, who is also the principal inventor of dupilumab.

According to the press release, children with EoE experience vomiting, abdominal pain, difficulty swallowing, and growth retardation, which impacts growth and development while causing related fear and anxiety. to food that may persist into adulthood.

Treatment consists primarily of dietary adjustments, in addition to proton pump inhibitors, swallowed topical corticosteroids, and in severe cases, feeding tubes to ensure proper calorie intake and weight gain. Yet about 9,000 of the approximately 21,000 children under the age of 12 in the United States with EoE do not respond satisfactorily to treatment.

“The lack of treatment options for children with eosinophilic esophagitis leaves many caregivers with the stress and burden of adjusting their child’s meals and the schedules of their entire family to ensure healthy growth and development. “, Namish Patel, MD, said the senior vice president, head of global development, immunology and inflammation at Sanofi in the press release.

“In some cases, they have to resort to off-label use of poorly studied treatments like steroids that can pose serious health risks when used long-term,” Patel continued.

The trial included 102 children aged 1 to 11 years who received a higher dose of dupilumab (n=37), a lower dose (n=31) or a placebo (n=34). Doses were subcutaneous and given every 2 or 4 weeks, depending on weight.

Namish Patel

“The faster and larger-than-expected enrollment in this trial further underscores the unmet treatment needs for children with EoE and highlights the importance of these early positive results,” Patel said.

At 16 weeks, 68% of the highest dose group and 58% of the lowest dose group achieved significant histological remission of disease, defined as a maximum esophageal intraepithelial eosinophil count of 6 eosinophils or less /high power field, versus 3% in the placebo group (both, P

Also at 16 weeks, children in the highest dose group experienced:

  • an 86% reduction in peak esophageal intraepithelial eosinophil count from baseline compared to a 21% increase for placebo (P
  • a 0.88 reduction in disease severity and a 0.84 reduction in disease extent from baseline, measured at the microscopic level in biopsy specimens, compared to an increase of 0.02 and 0.05 for placebo (both, P
  • a 3.5 point reduction from baseline in abnormal endoscopic findings compared to a 0.3 point increase for placebo (P
  • a numerical, but statistically significant, improvement from baseline in the proportion of days that children experienced EoE symptoms based on a caregiver questionnaire versus placebo; and
  • a 3.09 percentile increase from baseline in body weight for age percentile versus 0.29 for placebo.

Children in the low dose group also had nominally significant results in histological, anatomical and cellular secondary endpoints that were generally comparable to the higher dose, the researchers said.

The researchers also stated that the safety results were generally consistent with the known safety profile of dupilumab in the treatment of patients with EoE aged 12 years and older weighing at least 40 kg, with an event rate adverse event rate of 79% for dupilumab and an adverse event rate of 91% for placebo.

Adverse events more frequently observed with dupilumab than with placebo included COVID-19 (21% dupilumab, 0% placebo), 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).

The trial is continuing with an extended active treatment period of 36 weeks to assess long-term results. The companies said they would discuss their data with global regulators from the end of this year and share more detailed results at an upcoming medical meeting.


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