Future eosinophilic esophagitis treatments are currently in development. There are currently on FDA approved medications for the treatment of EoE. Commonly used treatments now are proton pump inhibitors, swallowed or topical corticosteroids and food elimination diets. Although each of these options is effective, there are limitations. Swallowed steroids can control inflammation 70-80% of the time, but steroid resistance, as well as loss of responsiveness can be seen up to 75% of the time. Food elimination diets can be effective, although no tests can accurately identify the triggering foods and long term adherence is difficult. Given these factors, future eosinophilic esophagitis treatment options are being studied.
Future Eosinophilic Esophagitis Biologic Therapies
This is a monoclonal antibody that binds to the alpha subunit of the IL4 receptor, resulting in blockage of both IL4 and IL13 pathways, and appears promising for modifying EoE. Dupixent is currently approved to treat asthma, eczema and nasal polyps. In phase 2 trials for EoE, patients had significant improvements in dysphagia, endoscopic findings and eosinophil counts. A phase 3 clinical trial is currently enrolling and completion is due in 2023.
2 EoE trials have been completed using IL-13 antibodies. The first studied was QAX576, which inhibits IL-13. In a study, treated adults had a 60% reduction in esophageal eosinophils. The second molecule, RPC4046 which prevents IL-13 binding. The treatment group led to a significant reduction in mean esophageal eosinophil counts with more than 50% having fewer than 15 eosinophils. Treated patients had improvements in endoscopic and histologic scoring as well as patient perceived disease severity. Additional trials are anticipated.
Several monoclonal antibodies target IL-5, mepolizumab, reslizumab and benralizumab. Mepolizumab and reslizumab act through direct binding to the IL-5 molecule, whereas benralizumab binds to the alpha subunit of the IL 5 receptor. Studies on mepliumab (Nucala) have shown reductions in tissue eosinophils, mast cell density and epithelial hyperplasia. Treated individuals also had improvements in clinical symptoms, endoscopic findings and reductions in blood eosinophils. Reslizumab studies in children have shown reduction in eosinophil counts, but no difference in clinical symptoms. Although studies for additional 6-7 years demonstrated improvement in clinical symptoms. No trials of benralizumab have been completed to date.
Siglecs play an important role in cell signaling and immune system regulation. Siglec-8 in humans is expressed by eosinophils, basophils and mast cells. Antibodies to Siglec has show reduction in inflammatory markers in the GI tract in mice.
A siglec-8 antibody, AK002 has completed a phase 2 trial in adults. At the end of the study, treated patients demonstrated a 95% reduction in tissue eosinophil compared to 10% in placebo. There were reduction in symptom scores as well.
Integrins play an important role in eosinophil trafficking especially in the GI tract. Vedolizumab is a monoclonal antibody that binds directly to integrins. Previous studies have shown some benefit but there are no current clinical trials.
Clinical trials of anti-IgE, Xolair have not shown it to be helpful, despite its role in asthma, allergic rhinitis and food allergy. Previous studies have shown it not to be successful in reducing tissue eosinophilia. There are currently no ongoing clinical trials of anti-IgE molecules for eosinophil GI tract disorders.
Corticosteroids remain the most common medical management option. Topical, swallowed preparations, including viscous budesonide are associated with improved outcomes in EoE. An orodispersible tablet of budesonide is currently approved for EoE in Europe. A phase 2b dose finding study on fluticasone dissolvable tablet in adults was recently reported.
Ongoing trials should pave the way for the first US FDA approved medication for EoE and help drive disease modification and prevent long term complications.