The US FDA approved Dupixent (dupilumab) developed by Regeneron as the first treatment for eosinophilic esophagitis, a chronic immune disorder that damages the esophagus.
Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease caused by type 2 (allergic) inflammation. An overreaction of the immune system recruits eosinophils, a type of white blood cell, to the esophagus, resulting in inflammation as they respond to the “threat”. This damages esophageal tissue over time, which complicates eating as even small amounts of food cause pain and present a choking hazard.
Understandably, being unable to eat results in frustration and a greatly reduced quality of life as patients must keep track of foods to avoid. EoE may necessitate painful dilation of a narrowed esophagus, or in extreme cases a feeding tube to ensure patients meet daily caloric requirements.
Although it is an underdiagnosed disease, approximately 160,000 people in the US live with EoE and their treatment options are not indicated for EoE specifically.
On Friday, Regeneron Pharmaceuticals, Inc. and Sanofi announced that Dupixent (dupilumab) has become the first and only medication indicated for treatment of EoE in the US after approval by the US Food and Drug Administration (FDA). Dupixent is approved for patients 12 years of age or older (weighing over 40 kg) at a dose of 300 mg per week. It is already approved for three other diseases, and EoE is the first gastrointestinal disease included in this group.
Monoclonal Antibody Technology Behind Dupixent’s Efficacy
Dupixent was developed with VelocImmune®, a human monoclonal antibody technology from Regeneron that inhibits interleukin-4 (IL-4) and IL-13 signaling pathways. These proteins cause the type 2 inflammation characteristic of EoE and related allergic diseases like asthma and atopic dermatitis (both treated with Dupixent).
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Clinical Trials of Dupixent for EoE Treatment
The approval of Dupixent is based on results from a randomized, double-blind, placebo-controlled Phase III clinical trial (NCT03633617) with two parts. Both studies evaluated the efficacy and safety of the treatment in EoE patients 12 years of age and older (weighing more than 40 kg). In Part A, 81 patients were enrolled, where 42 were given 300 mg of Dupixent weekly and 39 were given a placebo. Part B involved 159 patients, and evaluated the efficacy of 300 mg of Dupixent weekly in 80 patients and placebo in 79 patients.
At the end of both 24-week long trials, the primary endpoints assessed were patient-reported measures of difficulty swallowing and esophageal inflammation based on histological evidence of disease remission. In Part A and Part B, there was a 69 percent and 64 percent decrease of disease symptoms with Dupixent, respectively, compared to placebo results of 32 percent and 41 percent. The disease symptoms were measured using a Dysphagia Symptom Questionnaire filled out by patients to indicate difficulty swallowing. Additionally, histological results demonstrated that 60 percent and 59 percent of patients achieved disease remission in Part A and Part B, respectively, compared to the five percent and six percent receiving placebo — a tenfold difference.
The safety results of the trials were consistent with known adverse events from current approved indications of Dupixent. This includes injection site reactions, upper respiratory tract infections, joint pain and herpes viral infections. Ultimately, the trials demonstrated that 300 mg of Dupixent weekly significantly improves disease symptoms and emphasized the role of allergic inflammation in EoE.
Future Directions for EoE Treatment
“Before today, there were no approved treatments specifically for eosinophilic esophagitis, resulting in many people needing to maintain a strict diet and live in constant fear of food getting stuck in their throat. We welcome therapeutic options that can provide much-needed relief for these patients,” stated Mary Jo Strobel, Executive Director at the American Partnership for Eosinophilic Disorders in Regeneron’s press release.
While Dupixent was granted Priority Review by the FDA for this indication and will soon undergo regulatory review by the European Medicines Agency, other companies are also investigating potential treatments for EoE. For example, AstraZeneca is in the midst of Phase III trials using Fasenra (benralizumab, another monoclonal antibody) for the treatment of EoE. These treatment options will address the unmet need for those living with EoE and relieve symptoms, granting the ability to eat without the fear or pain of choking.