The New England Journal of Medicine has published results from a positive phase 3 trial showing adults and adolescents treated with Dupixent (dupilumab) 300 mg weekly experienced significant improvements in signs and symptoms of eosinophilic esophagitis (EoE), which were sustained for up to one year.
EoE is a chronic, progressive inflammatory disease that damages the esophagus and prevents it from working properly. These data formed the basis for the U.S. Food and Drug Administration (FDA) approval of Dupixent in May 2022, making it the first and only medicine indicated to treat patients with EoE aged 12 years and older, weighing at least 40 kg.
The phase 3 data have been submitted to the European Medicines Agency (EMA) to support regulatory approval for adults and adolescents with EoE. The EMA’s Committee for Medicinal Products for Human Use recently adopted a positive opinion recommending approval with a final decision expected in the coming months.
Evan S. Dellon, professor of gastroenterology and hepatology at the University of North Carolina School of Medicine, said: “The publication of these phase 3 results in the New England Journal of Medicine reinforces the impact of the clinical trial data. These data showed dupilumab 300 mg weekly substantially decreased patient symptoms of difficulty swallowing, and led to histological disease remission and improvements in the endoscopic appearance of the esophagus, as compared to placebo. These data also underscore the role of inhibiting the IL-4 and IL-13 pathways in eosinophilic esophagitis with dupilumab, adding to our growing knowledge of this poorly understood disease.”
Dupixent eosinophilic esophagitis study details
Patients received Dupixent 300 mg either weekly or every two weeks in the trial. Patients receiving Dupixent weekly experienced improvement in the ability to swallow and achieved histological disease remission. Additionally, these patients experienced improved anatomic, cellular, molecular and health-related quality of life measures, with improvements in signs and symptoms of EoE sustained for up to one year.
Patients treated with Dupixent every two weeks experienced histological disease remission but did not experience improvement in the ability to swallow. The current FDA-approved dosage for Dupixent as a treatment for children and adults aged 12 years and older with EoE, weighing at least 40 kg, is 300 mg weekly.
The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Adverse events more commonly observed with Dupixent included injection site reactions, nasopharyngitis and rash.
Dupixent is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases.
These diseases include approved indications for Dupixent such as asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyposis (CRSwNP), EoE and prurigo nodularis (PN).
Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE or PN in different age populations. Dupixent is currently approved across these indications in the U.S. and for one or more of these indications in more than 60 countries, including in the European Union and Japan. More than 500,000 patients have been treated with Dupixent globally.
Dupilumab development program
Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
In addition to the currently approved indications, Sanofi and Regeneron are studying dupilumab in a range of diseases driven by type 2 inflammation or other allergic processes in phase 3 trials. These include pediatric EoE, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritis of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis and bullous pemphigoid.
These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.