Few side effects, other than injection pain, emerged in the year-long phase 3 trial that convinced the Food and Drug Administration to approve the drug for EoE in May, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
The FDA approved dupilumab for the treatment of EoE in people 12 years and older who weigh at least 40 kg (about 88 pounds). The study included patients who had failed to benefit from an 8-week course of high-dose proton pump inhibitor (PPI) therapy, and most also hadn’t had relief from topical steroids.
Because dupilumab is a systemic biologic, such patients are the most likely candidates for the medication, Dr. Dellon said.
Dr. Dellon and colleagues published the study results in the New England Journal of Medicine.
A chronic, progressive, type 2 inflammatory disease of the esophagus, EoE can make it difficult to swallow and cause abdominal and chest pain or vomiting. Specialized diets, topical steroids, and PPIs can help manage EoE for many patients, but these therapies don’t always work, diets are difficult to follow, and topical steroids and PPIs can be difficult to take or cause side effects.
A fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi, dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, central drivers of type 2 inflammation in EoE. The FDA has approved dupilumab for atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
Three-part trial
For the three-part study conducted in Australia, Canada, Europe, and the United States, participants received 300 mg dupilumab by subcutaneous injection.
In part A, investigators randomly assigned 42 patients to weekly doses of dupilumab and 39 to weekly placebo injections for 24 weeks.
In part B, they randomly divided patients into three groups: Eighty received dupilumab weekly; 81 received dupilumab every 2 weeks; and 79 received a placebo weekly, for 24 weeks.
In part C, the intervention and placebo groups from part A received dupilumab weekly for another 28 weeks. For the two intervention groups in part B, treatment remained the same, while the part B placebo group was evenly split to receive dupilumab weekly or every 2 weeks for 28 weeks.
Over half of patients in remission
In part A, 60% of patients receiving weekly dupilumab achieved histologic remission (defined as no more than six eosinophils per high-power field), compared with 5% of patients receiving placebo, a significant difference (P < .001).
In part B, 59% of patients receiving weekly dupilumab, 60% of those receiving biweekly dupilumab, and 6% of those receiving placebo achieved histologic remission. The difference between those receiving weekly dupilumab or placebo was significant (P < .001).
Symptoms improved with weekly dupilumab, as measured via the Dysphagia Symptom Questionnaire score, which can range from 0 to 84, with higher values indicating more frequent or more severe dysphagia. The mean score at baseline was 33.6 in part A and 36.7 in part B. Scores in patients receiving weekly dupilumab decreased by 12.3 in part A and 9.9 in part B (both P < .001). However, among part B patients receiving biweekly dupilumab, the mean score dropped by only 0.5, which was not significant.
Dupilumab reached a higher serum concentration with the weekly than the biweekly regimen, which may explain the improved symptoms with more frequent dosing, Dr. Dellon said.
Only nine patients experienced serious adverse events during the part A or B treatment period (seven who received weekly dupilumab, one who received biweekly dupilumab, and one who received placebo) and just one patient during the part C treatment period who received placebo in part A and weekly dupilumab in part C. None of these events, except one, were related to the regimen, according to investigators.
Patients who received weekly dupilumab in part A and continued to part C maintained similar treatment effects to week 52, Dr. Dellon said. Although the data on part B patients who continued into part C were not included in the published paper, they were similar, he said.
“The people who responded to the first 24 weeks maintain that response for up to 52 weeks, and there was even a gain of response for some measures,” he said.
Patients, on average, also experienced improvements as measured by endoscopic healing, histological severity scores, and even gene expression, Dr. Dellon said.