Second Phase 3 Trial Shows Dupilumab Improves EoE in Patients 12 and Older

Adults and adolescents receiving dupilumab weekly for eosinophilic esophagitis (EoE) showed significant improvement in signs and symptoms of the disorder, with some achieving remission, according to findings presented Saturday afternoon at the American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting.

The results came from the second part of a phase 3 trial examining 300-mg weekly dupilumab compared with placebo at 24 weeks.

There are no treatments specifically approved to treat the type 2 inflammation believed to cause EoE, which affects about 160,000 patients in the United States. Triggered by food, EoE leads to many quality-of-life issues, as patients often wind up on restricted diets or liquid nutrition.

The results reported Saturday are part of the randomized, double-blind, placebo-controlled, phase 3 LIBERTY EoE TREET study (NCT03633617). Part A of the study, results of which have already been reported, examined subcutaneous injections of weekly dupilumab.

Patients were included in TREET if they were aged 12 and older with a documented diagnosis by endoscopic biopsy of EoE that has not responded to high-dose proton pump inhibitors.

Biopsies had to have shown a peak cell count ≥ 15 eosinophils per high power field (eos/hpf) in ≥ 2 of the 3 biopsied esophageal regions.

In addition, by patient report, they had to have had an average of 2 or more episodes of dysphagia per week while eating solid food in the 4 weeks prior to screening, as well as documented 4 or more episodes of dysphagia in the 2 weeks prior to baseline, at least 2 of which required liquids, coughing or gagging, vomiting, or medical attention. A Dysphagia Symptom Questionnaire (DSQ) score of 10 or more was also required.

Saturday’s part B results compared dupilumab, either weekly or every 2 weeks, with placebo weekly in a larger group of patients than in part A.

In part B, there were 79 patients in the placebo group and 80 patients in the group receiving 300-mg dupilumab. The majority were male and the mean age (SD) was 27.9 (12.6) years in the placebo group and 28.7 (13.7) years in the treatment group.

Results showed a 64% reduction in disease symptoms from baseline compared with 41% for placebo (P = .0008).

Patients in the treatment group also saw a 23.78-point improvement on the DSQ, compared with a 13.86-point improvement for placebo (P < .0001)

Compared with placebo, nearly 10 times as many patients receiving dupilumab reached histological disease remission, defined as ≤ 6 eos/hpf (P < .0001): 47, or 58.8%, of patients on the biologic compared with 5, or 6.3%, of those on placebo.

In addition, dupilumab reduced dysphagia symptoms by week 24 for a greater proportion of patients in the treatment group compared with the placebo group.

The most common adverse events were related to the injection site (reactions, erythema, and swelling). In part B, adverse events leading to discontinuation of the study were roughly the same in both the placebo group and the dupilmab group.

The study was funded by the makers of dupilumab, Regeneron and Sanofi, which are expected to file for approval for an EoE indication in the United States and globally this year.

Dupilumab received a Breakthrough Therapy Designation from the FDA for EoE in 2020.

Dupilumab, sold as Dupixent, targets interleukin (IL)-4 and IL-13 and is already approved for other type 2 atopic diseases, including moderate to severe atopic dermatitis in patients 6 years and older; in conjunction with other asthma drugs in patients 6 years and older for moderate to severe asthma; and with other medicines for chronic rhinosinusitis with nasal polyposis.