Weekly dupilumab may induce histologic remission of eosinophilic esophagitis
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PHOENIX — Dupilumab significantly improved swallowing ability and reduced eosinophils in the esophagus, indicating histologic remission, compared with placebo, according to results from the phase 3 LIBERTY-EoE-TREET study.
These results were presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
“Eosinophilic esophagitis (EoE) is a chronic, progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly,” Evan S. Dellon, MD, MPH, professor in the department of medicine, division of gastroenterology and hepatology at The University of North Carolina School of Medicine, told Healio.
“There is a high patient burden as the disease can greatly impact a person’s ability to eat normally. Symptom management may include invasive medical procedures to monitor the condition and, in more serious cases, to stretch the esophagus,” said Dellon, who also is the director of the Center for Esophageal Diseases and Swallowing at the school.
There are no current FDA-approved medicines for EoE, Dellon continued. However, dupilumab inhibits the signaling of the IL-4 and IL-13 pathways, which he called key and central drivers of type 2 inflammation.
In Parts A and C of the three-part, phase 3 LIBERTY-EoE-TREET study, researchers demonstrated the efficacy and safety of weekly 300 mg dupilumab (Dupixent, Regeneron/Sanofi) doses for 24 weeks, sustained up to 52 weeks.
Part B — presented here — involved 159 patients with EoE aged 12 years and older who received 300 mg dupilumab (n = 80; mean age, 28.7 years; 62.5% men) every week or every 2 weeks or placebo (n = 79; mean age, 27.9 years; 73.4% men) every week for 24 weeks. Patients assigned dupilumab and placebo had similar baseline characteristics, with mean eosinophils/high-power field (hpf) of 89.2 (standard deviation [SD], 46.7) vs. 84.3 (SD, 41.2) and mean Dysphagia Symptom Questionnaire (DSQ) scores of 38.4 (SD, 10.7) vs. 36.1 (SD, 10.6).
The proportion of patients achieving peak esophageal intraepithelial eosinophil counts of 6 eosinophils/hpf or fewer at week 24 — defined as histologic remission — and the absolute change in DSQ score from baseline to week 24, served as the study’s coprimary endpoints.
At week 24, 58.8% of the participants on weekly dupilumab achieved histologic remission, compared with 6.3% of the participants on placebo (P < .0001).
Also, the least squares mean absolute changes in DSQ score were –23.78 (standard error [SE], 1.86) for weekly dupilumab and –13.86 (SE, 1.91) for placebo (P < .0001).
Researchers also reported a 64% reduction in disease symptoms from baseline among the participants receiving weekly dupilumab compared with 41% for placebo (P = .0008).
Treatment-emergent adverse events occurred among 83.8% of the dupilumab cohort and 70.5% of the placebo cohort. These most commonly included injection site reactions (37.5% for dupilumab vs. 33.3% for placebo) and fever (6.3% vs. 1.3%). There were no deaths.
These results match the results of Part A of the study, the researchers said.
“The results of the trial showed that dupilumab 300 mg weekly significantly improved the signs and symptoms of EoE at 24 weeks compared with placebo in patients aged 12 years and older, improving the ability to swallow,” Dellon said.
“There was also a significant effect on the inflammation, with nearly 10 times as many patients receiving dupilumab achieving histological disease remission compared with placebo,” he continued. “Dupilumab also demonstrated generally consistent safety results with its known profile in its approved indications.”
Noting that there are no approved EoE treatments that address the underlying drivers of the disease, the researchers said that dupilumab is the only biologic medicine that has had positive, clinically meaningful phase 3 results among adults and adolescents.
However, Dellon cautioned that there have been no head-to-head trials between dupilumab and any other potential treatment for EoE and that the patient populations in different trials also differ, so it’s hard to make a direct comparison.
The researchers now expect there to be regulatory filings in the U.S. and around the world this year. Meanwhile, the clinical trial program is ongoing, with patients from Part A and B of continuing into the Part C 28-week long-term extension trial. Additional results from this trial will be presented at a future medical meeting, Dellon said.
“There is a significant unmet treatment need for people with EoE, for whom swallowing food or taking a sip of water can be a painful and worrisome choking experience,” he said. “Over time, excessive type 2 inflammation causes scarring and narrowing of the esophagus, making it difficult to swallow.
“This disease can also cause narrowing of the esophagus and dilation (physical expansion) of the esophagus may be needed, which is often painful,” he continued. “Therefore, these results are encouraging, indicate that targeting type 2 inflammation in clinical care leads to a benefit in EoE and suggest dupilumab is an effective treatment for EoE.”