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FDA approves first drug for eosinophilic esophagitis

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This marks a paradigm shift

Eosinophilic esophagitis (EoE) is a chronic disease requiring long-term treatment for both induction and maintenance of response. For decades, however, Food and Drug Administration–approved therapies for EoE have not been available. Dupilumab is the first drug to receive FDA approval to treat EoE. This human monoclonal antibody directed against the interleukin (IL)4 receptor–alpha component of the type 2 receptor inhibits signaling of IL4 and IL13. Dupilumab has shown efficacy in similar diseases, such as atopic dermatitis and eosinophilic asthma. In 2017 dupilumab was granted Orphan Drug designation for the potential treatment of EoE and in 2020 the FDA granted Breakthrough Therapy designation for EoE. Recent data from the phase 3 trial of dupilumab 300 mg weekly enrolling patients aged 12 years and older demonstrated a significantly greater reduction in disease symptoms, normalization of esophageal eosinophilia, and reduction in endoscopic findings by week 24 compared with placebo.

The highly anticipated approval of dupilumab marks a paradigm shift toward biologic medications for treatment of EoE when historical treatments have relied on proton pump–inhibitor therapy or topical swallowed steroids. As we await updates about availability and access of dupilumab for our patients, we can rest assured that a highly efficacious treatment is now approved and will fill an important treatment gap in EoE, particularly for patients not deriving adequate response with traditionally used strategies. With multiple clinical trials underway, this milestone likely represents the beginning of additional effective therapies (nonbiologic and biologic) that will be available for EoE.

Rena Yadlapati, MD, MSHS, FACG, is associate professor of clinical medicine in the division of gastroenterology at the University of California, San Diego, medical director of the UCSD Center for Esophageal Diseases, and director of the GI Motility Lab. She has no relevant conflicts of interest.


 

The U.S. Food and Drug Administration has approved dupilumab (Dupixent, Regeneron) to treat eosinophilic esophagitis (EoE) in adults and children aged 12 years and older weighing at least 40 kg.

EoE is a chronic inflammatory disorder driven by type 2 inflammation that damages the esophagus and causes difficulty swallowing and eating.

Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. It’s the first drug to be approved by the FDA for EoE.

In a phase 3 trial, dupilumab 300 mg weekly significantly improved signs and symptoms of eosinophilic esophagitis, compared with placebo, underscoring the role of type 2 inflammation in this disease, Regeneron says in a news release.

According to the company, there are roughly 160,000 patients in the United States living with EoE who are currently using treatments not specifically approved for the disease. Of those patients, about 48,000 continue to experience symptoms despite multiple treatments.

“As researchers and clinicians have gained knowledge about eosinophilic esophagitis in recent years, more cases of the disorder have been recognized and diagnosed in the U.S.,” Jessica Lee, MD, director of the Division of Gastroenterology in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release.

The approval of dupilumab will “fulfill an important unmet need for the increasing number of patients with eosinophilic esophagitis,” Dr. Lee said.

The efficacy and safety of dupilumab in EoE was demonstrated in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial that included two 24-week treatment periods (parts A and B) that were conducted independently in separate groups of patients.

In both part A and B, patients received dupilumab 300 mg or placebo every week.

In part A of the trial, 60% of the 42 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 5% of the 39 patients who received placebo, the FDA said.

Patients who received dupilumab also experienced an average improvement of 22 points in the Dysphagia Symptom Questionnaire (DSQ) score, compared with 10 points for patients who received placebo.

In part B, 59% of the 80 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 6% of the 79 patients who received placebo.

Patients who received dupilumab also experienced an average improvement of 24 points in their DSQ score, compared with 14 points for patients who received placebo.

“Assessments incorporating the perspectives from patients with EoE supported that the DSQ score improvement in patients who received Dupixent in the clinical trial was representative of clinically meaningful improvement in dysphagia,” the FDA noted.

“Treatment for patients with eosinophilic esophagitis can be challenging, particularly with no previously approved medications,” Evan Dellon, MD, principal investigator for the phase 3 trial, said in the company news release.

“Now, patients and their doctors have a treatment option available as part of their management plan that has the potential to control symptoms, improve inflammation, and heal the changes in the esophagus caused by this progressive and burdensome disease,” added Dr. Dellon, who is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

The FDA granted dupilumab priority review and breakthrough therapy designations for EoE.

Dupilumab is already approved in the United States for treatment of moderate to severe atopic dermatitis in adults and children aged 6 years and older whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not advisable.

The drug is also approved as an add-on maintenance treatment for adults and children aged 6 years and older with certain types of moderate to severe asthma and as an add-on maintenance treatment for adults with inadequately controlled chronic rhinosinusitis with nasal polyposis.

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