New pooled phase 3 data presented at ACAAI 2022 supports the FDA's approval of dupilumab for eosinophilic esophagitis.
Weekly 300 mg dupilumab (Dupixent) provided significant and clinically meaningful improvement to patient histologic and endoscopic outcomes in adult and adolescent patients with eosinophilic esophagitis (EoE), according to findings from a new study.
In new data presented at the American College of Allergy, Asthma and Immunology (ACAAI) 2022 Annual Meeting this week, a team of investigators from the Sanofi and Regeneron-sponsored LIBERTY-EoE-TREET trial reported that the type 2 inflammation-targeting dupilumab provides both disease- and symptom-related benefits in patients with EoE.
The complete data were among the supporting evidence in the companies’ US Food and Drug Administration (FDA) submission for dupilumab as a marketed therapy for the treatment of EoE in patients ≥12 years old.
Led by Evan S. Dellon, MD, MPH, director of the Center for Esophageal Diseases and Swallowing School of Medicine at the University North Carolina at Chapel Hill, investigators provided a report on the pooled results of the two-part, phase 3 trial assessing once-daily 300 mg dupilumab in patients with EoE.
As a chronic, inflammatory esophageal disease that causes dysfunction and burdens on quality of life, EoE currently has a field of treatment options that “lack specificity, present adherence
challenges, and/or may offer suboptimal long-term disease control.” Dellon and colleagues noted that dupilumab, the recently FDA-approved option, provides inflammatory and symptomatic benefit through its inhibition of the IL-4 and IL-13 pathways.
Parts A and B of the LIBERTY-EoE-TREET assessment showed benefit with dupilumab in the symptomatic, histologic, and endoscopic components of EoE in treated patients over 24 weeks. The injection biologic was additionally well tolerated.
The TREET study sought primary endpoints of proportion of patients achieving peak esophageal intraepithelial eosinophil counts of ≤6, plus absolute change in Dysphagia Symptom Questionnaire (DSQ), at week 24. Investigators additionally sought key secondary endpoints of percent change in peak esophageal intraepithelial eosinophil count, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (HSS) grade score, and absolute change in EoE-HSS stage score, each from baseline to week 24.
Recruited patients were aged ≥12 years old with EoE that has not responded to high-dose proton pump inhibitors, as well as with baseline DSQ scores ≥10, among other parameters of disease burden.
The team randomized patients to 300 mg dupilumab (n = 122) or placebo (n = 118). Mean patient age in the dupilumab arm was 30.5 years old, 36.1% being female. 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 59.0% and 77.0% of patients receiving dupilumab 300 mg achieved peak esophageal eosinophil counts of ≤6 and ≤15, respectively, at week 24. Percent change in esophageal eosinophil count was -80.1% in the treatment arm, versus 1.54% in the placebo arm, at week 24 (P <.0001).
Dellon and colleagues additionally observed significant reductions in both HSS grade and stage scores in the dupilumab arm versus placebo, as well as reduced dysphagia symptoms per DSQ at week 24 (P <.0001).
Regarding safety, investigators observed treatment-emergent adverse events (TEAEs) in 84.4% of patients receiving dupilumab versus 74.4% of patients receiving placebo. Just 5.7% and 1.7% of patients reported severe events, respectively; the most common TEAE in patients receiving dupilumab included injection-site reaction (19.7%) and swelling (12.3%).
“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, 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.”
The study, “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,” was presented at ACAAI 2022.