EoE KIDS: Higher Exposure Dupilumab Improves Histologic, Endoscopic Outcomes

Mirna Chehade, MD, MPH

Credit: Mount Sinai

Higher exposure dupilumab demonstrated both improved histologic and endoscopic outcomes in children <12 years with eosinophilic esophagitis (EoE) at 52 weeks of the phase 3 EoE KIDS Trial, according to data presented at Digestive Disease Week (DDW) 2024.¹

In January 2024, the US Food and Drug Administration (FDA) approved dupilumab for treating pediatric patients aged 1 to 11, weighing ≥15 kg, with EoE.² This marked the first and only medicine approved in the US to treat this age range with EoE.

“Higher-exposure dupilumab improved histologic and endoscopic measures of EOE versus placebo in children with EOE aged 1 to <12 years,” said Mirna Chehade, MD, MPH, Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai.¹ “High-exposure dupilumab also led to numeric improvements in EOE signs and body weight for age percentile.”

A chronic, progressive type 2 inflammatory disease, EoE is experiencing an increase in its incidence and prevalence, a notable facet due to the disease’s significant impact on quality of life.³ FDA approval was based on data from the Phase 3 EoE KIDS trial—the trial measured the efficacy and safety of dupilumab, compared with placebo, in a pediatric population with active EoE aged 1 to <12 years.²

Part A of EoE KIDS was a 16-week, placebo-controlled study in which patients were randomized 2:2:1:1 to a weight-tiered, subcutaneous dupilumab with a higher- or lower-exposure treatment regimen, or to a placebo cohort with higher or lower exposure.

Children who completed Part A could enter Part B of EoE KIDS, an extended active treatment period to Week 52 where patients in the dupilumab cohort continued the same regimen. Patients initially treated with placebo received dupilumab at the equivalent exposure assigned at randomization.

At Week 16 in Part A of EoE KIDS, approximately two-thirds (67.6%) of patients treated with higher-exposure dupilumab achieved the primary endpoint of peak esophageal intraepithelial eosinophil (eos) count ≤6 eos/high-power field (hpf) (20 eos/mm2) compared with 2.9% in the placebo cohort (P <.001).

By Week 52, 62.9% of children treated with higher-exposure dupilumab in Parts A and B, and 52.9% of patients who switched from placebo to higher-exposure dupilumab in Part B, demonstrated a peak eos/hpf ≤6.

Measurements by the Pediatric EoE Signs/Symptoms Questionnaire–Caregiver version (PESQ-C) revealed the least-squares (LS) mean difference versus placebo in the number of days with ≥1 EoE sign was –0.10 (95% CI, –0.24 to 0.04), equivalent to –1.4 days, in those treated with higher exposure dupilumab at Week 16. Across the duration of Part B, continuous treatment with higher exposure dupilumab treatment reduced EoE signs.

Overall, higher exposure dupilumab was associated with improvements in endoscopic, histologic, and symptomatic outcomes, along with body weight for age percentile, versus placebo at week 16. These benefits were maintained with continuous dupilumab treatment and improved for the switching cohort through week 52.

Across the treatment period, the incidence of adverse events was 73 to 100% across both trial groups and trial periods. In Part A, no discontinuations linked to adverse events in the dupilumab-treated cohort were identified, while two events led to discontinuation in the placebo group. In Part B, a single adverse event led to discontinuation in a patient who remained on higher exposure dupilumab.

“Dupilumab was well-tolerated, and the safety profile was similar to the safety profile seen in adult and adolescent patients with EoE,” Chehade added.

References

1. _{Chehade M, Dellon ES, Spergel J, Rothenberg ME, Pesek R, Collins MH, Hirano I, et al. Dupilumab Improves Histologic and Endoscopic Outcomes in Children Aged 1 to <12 Years with Eosinophilic Esophagitis (EoE): 52-week Results from the Phase 3 EoE KIDS Trial. Poster presented at Digestive Disease Week 2024, May 18 - 21, 2024.}
2. _{Press release: DUPIXENT® FDA approved as first and only treatment indicated for children aged 1 year and older with eosinophilic esophagitis (EOE). Sanofi. January 25, 2024. Accessed May 18, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-01-25-19-30-00-2817342.}
3. _{Bredenoord AJ, Patel K, Schoepfer AM, et al. Disease Burden and Unmet Need in Eosinophilic Esophagitis. Am J Gastroenterol. 2022;117(8):1231-1241. doi:10.14309/ajg.0000000000001777}