New York-based biotechnology company Regeneron (NASDAQ: REGN) and French pharmaceutical company Sanofi (NASDAQ: SNY) have announced the results of Part A of a phase 3 clinical trial evaluating the safety and efficacy of the antibody inhibitor Dupixent (dupilumab) for treating Eosinophilic Esophagitis (EoE) in adolescents and adults.
The randomized, placebo-controlled, double-blind phase 3 clinical trial involved the weekly subcutaneous administration of Dupilumab 300 mg or a placebo to 81 patients with Eosinophilic Esophagitis for 24 weeks.
After the cessation of treatment, clinical outcomes were assessed by evaluating the number of esophageal intraepithelial eosinophils, “a measure of esophageal inflammation,” and the difficulty that patients experienced swallowing, as determined by the Dysphagia Symptom Questionnaire.
After 24 weeks, treatment with Dupixent was associated with a statistically significant reduction in three measures of disease severity: disease symptoms, esophageal eosinophilic count, and “abnormal endoscopic findings” based on the EoE Endoscopic Reference Score.
The safety profile of the medication for the treatment of EoE and other indications were found to be similar, according to the press release, with adverse events including injection site reactions, infections of the upper respiratory tract, and arthralgia.
Co-Founder, President, and Chief Scientific Officer of Regeneron George D Yancopoulos, MD, PhD, stated, “Eosinophilic esophagitis can be debilitating, and there are no approved treatment options. It impacts patients’ ability to eat, causes severe pain and often results in repeated emergency room visits and medical procedures. These data are particularly impressive, as Dupixent not only dramatically reduced eosinophils in the esophagus, but also improved all clinical, anatomic and histologic measures of the disease.”
“In the past, EoE was thought to be a disease caused by eosinophils, but other biologics that decrease eosinophils in the esophagus did not demonstrate consistent clinical or anatomical improvements. These Dupixent results demonstrate EoE is caused by multiple aspects of type 2 inflammation, driven by interleukin-4 and interleukin-13. EoE is the fourth atopic or type 2 inflammatory disease in which Dupixent has pivotal data demonstrating significant efficacy,” Dr. Yancopoulos continued.
Sanofi’s Global Head of Research and Development John Reed, MD, PhD, stated, ”These data demonstrate Dupixent’s potential to continue to address treatment gaps across the spectrum of type 2 inflammatory diseases as common as asthma and as rare as eosinophilic esophagitis. For the first time in a Phase 3 trial, patients reported an improvement in their ability to swallow food.”
“For patients with eosinophilic esophagitis who are living with restricted diets and, in some cases, repeated hospital interventions, these findings are encouraging,” Dr. Reed continued.
Eosinophilic Esophagitis is a chronic immune-mediated inflammatory disorder associated with the concentration in the esophagus of eosinophils, a subset of immune cells implicated in allergic responses and asthma. EoE is thought to result from a combination of genetic and environmental factors, including food or environmental antigens such as pollen, that lead to a pathogenic immune response.
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The disease is highly debilitating, potentially leading to difficulty swallowing and food compaction in the upper gastrointestinal tract, which requires emergency treatment.
Dupixent (dupilumab) is a fully-human monoclonal antibody inhibitor of the interleukin-4 (IL-4) receptor alpha, a protein expressed on the surface of certain immune cell populations that induces the activation and weaponization of these cells following recognition of the cytokines IL-4 and IL-13.
By binding to and inhibiting the activity of the IL-4 receptor alpha, Dupixent ameliorates the damaging inflammatiion and type 2 immune responses characteristic of EoE.
Dupixent was designated by the United States Food and Drug Administration in 2017 as an orphan drug “for the potential treatment of EoE.” The medication is also used to treat other immune-mediated disorders including eczema.
There are currently no FDA-approved medications for the treatment of EoE. Approximately 160,000 individuals are being treated for the disease in the United States and 50,000 have failed treatment.
Other therapies targeting immune-related proteins are also under investigation, such as Gilead’s Filgotinib which has been studied in a phase 2b/3 clinical trial for the treatment of Ulcerative Colitis.