Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.
The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
Dr. Evan S. Dellon
In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).
“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”
EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.
Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
Study population difficult to treat
In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.
Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.
On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.
Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.
Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.
The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
Pooled parts A and B findings
Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.
Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.
In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.
Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.
“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.