Weight-tiered higher doses of dupilumab improves key disease measures of EoE

Weight-tiered higher doses of dupilumab improves key disease measures of EoE | Image Credit: © Yurii Kibalnik - © Yurii Kibalnik - stock.adobe.com.

New data for FDA-approved dupilumab (Dupixent; Regeneron and Sanofi) have been published in The New England Journal of Medicine (NEJM), highlighting positive study results for the eosinophilic esophagitis (EoE) treatment in children aged 1 to 11 years, according to a press release from Sanofi.^1,2

Study results, which led to Priority Review and approval from the FDA, demonstrated that a greater proportion of patients who received a weight-tiered, higher dose of dupilumab experienced improvements in key disease measures of EoE compared to placebo at a 16-week mark.¹

The monoclonal antibody blocks interleukin-4 and interleukin-13 pathways and has demonstrated efficacy in EoE in adults and adolescents, as well as 4 other atopic diseases marked by type 2 inflammation, wrote the NEJM study investigators.²

In a phase 3 trial, the investigative team randomly assigned active EoE patients aged 1 to 11 years who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A) in a 2:2:1:1 ratio.²

At the conclusion of Part A, eligible patients in each dupilumab group continued the same regimen, with those in the place groups assigned to higher- or lower-exposure dupilumab for 36 weeks (Part B). Dupilumab was administered in 1 of 4 doses tiered according to baseline body weight at each level of exposure. Histologic remission, defined as peak esophageal intraepithelial eosinophil count, ≤6 per high-power field at week 16, was the primary outcome of the trial.

Histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group in Part A. Remission also occurred in 18 of 31 (58%) patients in the lower-exposure group, and in 1 of 34 (3%) in the placebo group. The difference between the higher-exposure regimen and placebo was 65% (95% CI, 48 to 81; [P < 0.001]). Between the lower-exposure regimen and placebo, the difference was 55% (95% CI, 37 to 73 [P < 0.001]).²

Significant improvements were observed in the higher-exposure dupilumab regimen for histologic, endoscopic, and transcriptomic measures compared to placebo.²

"The NEJM publication of these phase 3 dupilumab results is a testament to the importance of these data and potential for dupilumab to change the standard of care for many young children living with [EoE]," said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York, and principal investigator of the study.

"These children commonly experience feeding difficulties, food refusal and failure to thrive during a critical time of their growth and development. These data showed weight-tiered higher dose dupilumab significantly improved key eosinophilic esophagitis histologic, endoscopic, and cellular measures in children as young as 1 year old with sustained results for up to one year. These results reinforce the positive results seen in older patients with eosinophilic esophagitis and strengthen our understanding of IL4 and IL13 as key drivers of the type 2 inflammation underlying this disease," said Chehade in a press release from Sanofi.¹

Dupilumab was approved for children with EoE aged 1 to 11 years who weigh at least 33 lbs (15 kg) on January 25, 2024. This decision expanded on the initial approval for EoE in patients 12 years and older who weighed at least 88 lbs (40 kg).³

Vivian Hernandez-Trujillo, MD, FAAP, FAAAAI, FACAAI

"This is a safe treatment option for children as young as 1 year old. The weekly injection decreases the underlying inflammation in EoE. Histologic remission was seen in 1/2 to 2/3 of patients, and this is important in preventing the long-term complications associated with inflammation in EoE," Vivian Hernandez-Trujillo, MD, FAAP, FAAAAI, FACAAI told Contemporary Pediatrics at the time of FDA approval.

"This treatment gives families of the youngest pediatric patients another option for a disease that is, often, challenging to treat."⁴

Click here for the full FDA approval reaction.⁴

References:

1. Dupixent positive phase 3 data in children one to 11 years of age with eosinophilic esophagitis published in NEJM. Sanofi. June 26, 2024. Accessed June 27, 2024. https://www.news.sanofi.us/2024-06-26-Dupixent-positive-phase-3-data-in-children-one-to-11-years-of-age-with-eosinophilic-esophagitis-published-in-NEJM
2. Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for eosinophilic esophagitis in patients 1 to 11 years of age. N Engl J Med. 2024;390(24):2239-2251. doi:10.1056/NEJMoa2312282
3. Fitch, J. FDA approves dupilumab for eosinophilic esophagitis in children aged 1 to 11 years. Contemporary Pediatrics. January 25, 2024. Accessed June 28, 2024. https://www.contemporarypediatrics.com/view/fda-approves-dupilumab-for-eosinophilic-esophagitis-in-children-aged-1-to-11-years
4. Fitch, J. Reaction to FDA approved dupilumab for eosinophilic esophagitis in children. Contemporary Pediatrics. February 1, 2024. Accessed June 28, 2024. https://www.contemporarypediatrics.com/view/reaction-to-fda-approved-dupilumab-for-eosinophilic-esophagitis-in-children