Dupilumab's effectiveness is due to the monoclonal antibody's ability to rapidly reduce inflammation.
Dupilumab, approved by FDA earlier this year to treat eczema, is showing promise as a treatment for a chronic condition of the esophagus typically caused by food allergies, based on results of a phase 2 study released Monday.
Results reported Monday at the World Congress of Gastroenterology in Orlando, Florida, showed that patients with moderate-to-severe eosinophilic esophagitis showed significant improvement in their ability to swallow after taking dupilumab, compared with those taking placebo, as measured by a standard diagnostic scale.
As the number of patients with allergies increases, so are cases of eosinophilic esophagitis. This chronic disease is marked by high levels of eosinophils in the esophagus, which may be a biomarker of broader type 2 inflammation.
This new study suggests that dupilumab’s ability to quickly reduce inflammation, which makes it so effective in clearing up atopic dermatitis (eczema), appears to be at work in reversing type 2 inflammation in eosinophilic esophagitis. Dupilumab works by targeting and limiting the overactivity of interleukins (IL) 4 and 13, which cause type 2 inflammation.
The study randomized 47 patients into 2 groups, with the primary endpoint being the rating on the 9-point Straumann Dysphagia Instrument (SDI) Score, a patient-reported measure of swallowing difficulty. At baseline, patients had a mean score of 6.4. Patients received a loading dose of 600 mg of dupilumab, followed by weekly doses of 300 mg, or placebo. At week 10, patients who had received the study drug reported a 3-point reduction in their SDI score, for a 45% improvement, compared with a 1.3-point reduction, or a 19% improvement, in the placebo group.
Secondary endpoints included measures of disease severity and symptoms. On a visual scale of disease severity, patients in the dupilumab group saw their disease severity drop 93% by week 12, compared with an increase of 14% in those taking placebo. In a composite measure of symptom improvement and quality of life, patients taking dupilumab saw a 35% improvement, compared with 11% improvement for those taking placebo.
“Clinical manifestations of eosinophilic esophagitis in adults include difficulty swallowing and food impaction, which are consequences of pathological structural changes to the esophagus. Natural history studies have demonstrated an association between duration of untreated disease and the development of these esophageal changes,” Ikuo Hirano, MD, professor of medicine, Northwestern University Feinberg School of Medicine, said in a statement.
“Currently, there are no FDA-approved therapies for eosinophilic esophagitis. In this study, dupilumab, a monoclonal antibody targeting IL-4 and IL-13, significantly improved patients’ ability to swallow, inflammation of the esophagus, and endoscopic signs of the disease,” Hirano said. “These positive phase 2 results support further clinical development of dupilumab for patients with eosinophilic esophagitis.”
Dupilumab, sold for treatment of atopic dermatitis (eczema) as Dupixent, is jointly developed by Sanofi and Regeneron.