PHOENIX — New results from a separate, larger phase 3 trial confirm the benefits of dupilumab (Dupixent) in adults and adolescents with eosinophilic esophagitis (EoE), showing that weekly injections of the biologic sent 59% of EoE patients into disease remission after 24 weeks. The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks IL-4 and IL-13, two parts of the type 2 immune response, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab vs placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
"These results replicate those in Part A in a larger sample size," reported Marc Rothenberg, MD, PhD, director of the Division of Allergy and Immunology at Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, in a pre-recorded presentation.
Based on the phase 3 data, dupilumab seems "effective for patients who may have no other options for managing their EoE," Brian Schroer, MD, director of allergy and immunology at Akron Children's Hospital in Akron, Ohio, told Medscape Medical News. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the pre-recorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B's second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to patients who received weekly dupilumab, though symptoms "did not meet statistical significance," he said. "I think we're going to have much more detail about those results at some conferences to come in the spring."
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dellon has received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GlaxoSmithKline (GSK), Meritage, Miraca, Nutricia, Celgene /Receptos/ BMS, Regeneron, and Shire /Takeda; consulting fees from Abbott, AbbVie, Adare/Ellodi, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi, Calypso, Celgene /Receptos/ BMS, Celldex, Eli Lilly, EsoCap, GSK, Gossamer Bio, Landos, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, and Shire /Takeda; and educational grants from Allakos, Banner, and Holoclara.
Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Bristol Myers Squibb, AstraZeneca, Ellodi Pharma, GlaxoSmithKline, Regeneron/Sanofi, Revolo Biotherapeutics, Nextstone One, and Guidepoint and has an equity interest in the first six listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. He is an inventor of patents owned by Cincinnati Children's Hospital.
Schroer has received consulting fees from Sanofi and Ready, Set, Food.
American Academy of Allergy, Asthma and Immunology (2022) Annual Meeting: Abstract presented February 26, 2022.
Esther Landhuis is a freelance science journalist in the San Francisco Bay Area. She can be found on Twitter @elandhuis.
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Image1: Cincinnati Children's Hospital Medical Center
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Cite this: Dupilumab Shows Histological and Clinical Benefit in Larger Eosinophilic Esophagitis Cohort - Medscape - Mar 03, 2022.