Dupilumab Pooled Phase 3 Trial Data Broadly Support FDA Approval for EoE

Weekly dupilumab 300 mg was associated improved clinical, symptomatic, histologic, and endoscopic features of eosinophilic esophagitis (EoE) up to 24 weeks in adults and adolescents, according to pooled data from the pivotal phase 3 LIBERTY-EoE-TREET study.

The findings from the analysis were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2022 Annual Scientific Meeting held in Louisville, KY, November 10-14, 2022.

Complete data from the LIBERTY-EoE-TREET study were the basis for the FDA approvalof dupilumab to treat adults and adolescents (aged ≥12 years and weighing ≥40 kg) with EoE. The approval, granted in May 2022, was the first dedicated specifically for EoE and followed FDA’s designation of dupilumab as a breakthrough therapy and a priority agency review.

Chronic and progressive, EoE is a type-2 inflammatory disease in which cytokines interleukin (IL)-4 and IL-13 along with other inflammatory cells contribute to esophageal remodeling, stricture formation, and fibrosis. The resulting esophageal dysfunction can significantly affect quality of life, according to study authors led by Evan S. Dellon, MD, MPH, professor of medicine and adjunct professor of epidemiology in the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine. Some current treatment options, the authors note, lack specificity and provide suboptimal long-term disease control. Dupilumab reduces inflammation and symptoms through targeted inhibition of the IL-4 and IL-13 pathways.

The current findings are pooled results from parts A and B of the 3-part LIBERTY-EoE-TREET study that originally evaluated the efficacy and safety of weekly dupilumab 300 mg vs placebo in adult and adolescent patients with EoE for 24 weeks.

Study participants were aged ≥12 years with EoE unresponsive to high-dose proton pump inhibitors and with baseline Dysphagia Symptom Questionnaire (DSQ) scores ≥10, among other clinical characteristics.

Study endpoints, assessed at week 24, were the proportion of study participants achieving peak eosinophil counts of ≤6/high power field (hpf); absolute and percentage change in DSQ score; percent change in peak eosinophil count; absolute change in Histologic Scoring System (HSS) grade and stage scores and Endoscopic Reference Score (EREFS); proportion of patients achieving peak eosinophil count <15/hpf.

Investigators randomized patients to 300 mg dupilumab (n = 122) or placebo (n = 118). Mean age of participants receiving dupilumab was 30.5 years and the group was comprised of 36.1% women. Mean duration of EoE was 5.7 years; 68.9% of patients had a history of prior swallowed topical corticosteroids for their disease. Common comorbid atopic conditions included allergic rhinitis (61.5%), asthma (41.8%), atopic dermatitis (21.3%), and food allergy (28.7%).

Investigators reported that at 24 weeks, patients in the dupilumab 300 mg arm vs the placebo group achieved greater:

• peak eosinophil counts of ≤6/hpf (59% vs 5.9%)
• absolute change in DSQ score (–23.2 vs –12.7)
• percent change in DSQ (–65.5% vs –38.2%)
• percent change in peak eosinophil count (–80.1% vs 1.5%)
• proportion of patients achieving eosinophils counts ≤15/hpf (77% vs 7.6%)
• absolute change in HSS grade (–0.82 vs –0.1)
• absolute change in HSS stage scores (–0.79 vs –0.09)
• change in EREFS score (–3.95 vs. –0.41) (all P<.001)

Regarding safety, investigators reported that dupilumab was “generally well tolerated,” with the most common treatment-emergent adverse event being injection site reaction (19.7% vs 17.9% for placebo).

“The pooled data from Part A and Part B of the 3-part, phase 3 LIBERTY EoE TREET study indicate that weekly dupilumab 300 mg vs placebo demonstrated statistically significant and clinically meaningful improvements in histologic and endoscopic outcomes and symptoms in adults and adolescents with EoE,” investigators wrote. “Overall safety was consistent with the known dupilumab safety profile.”

Abstract reference: Dellon E, Rothenberg M, Bredenoord A, et al. Dupilumab improves clinical symptomatic, histologic, and endoscopic aspects of EoE up to 24 weeks: pooled results from parts A and B of phase 3 LIBERTY-EoE-TREET. Abstract presented at the American College of Allergy, Asthma, and Immunology 2022 Scientific Meeting; November 10-14, 2022; Louisville, KY.