Clinical Trials in Eosinophilic Esophagitis (EoE) - Advances and Opportunities with this Rare Disease


Eosinophilic esophagitis (EoE) is a rare esophageal condition that currently has no FDA-approved medications resulting in major gaps in treatment. Therefore, the need for better options and opportunities for drug development is apparent.

This blog is the first in a series on drug development in gastroenterology from experts at the American Gastroenterological Association Center for Diagnostics and Therapeutics. If you’re interested in learning more about drug development in this area, join the center for its first Drug Development Conference, Oct. 27-28, 2016, in Washington, DC.Eosinophilic esophagitis (EoE) is a chronic immune/allergen-mediated condition defined clinically by symptoms of esophageal dysfunction and histologically by a marked eosinophilic infiltration of the esophageal mucosa. EoE affects all ages. In adolescents and adults, symptoms of dysphagia and food impaction are most common. In children, symptoms can include heartburn, abdominal pain, regurgitation/vomiting, feeding intolerance and failure to thrive. The first line pharmacologic therapies for EoE are corticosteroids that are used “topically” - asthma preparations such as fluticasone or budesonide are swallowed rather than inhaled to coat the esophageal and provide a local anti-inflammatory effect. However, there are several issues that make this approach sub-optimal. First, these medications are formulated for pulmonary, not esophageal, deposition. Second, they are currently used off label; there are no FDA-approved medications for EoE. Third, they do not directly target the known pathogenesis of EoE. Finally, though supported by a robust evidence base, less than 60% to 70% of EoE patients, on average, respond to these medications. Therefore, there is a marked need for better options and a clear opportunity for drug development.

The first randomized clinical trial in EoE, which assessed the efficacy of swallowed fluticasone, had results published only in 2006. Since that time, there have been a number of additional published trial results using topical steroids, biologic agents and novel small molecules. As of this writing, there are nearly 40 ongoing clinical trials listed on that are being conducted both in academia and by industry, including the first phase III trial in EoE. There are at least two major reasons for this tremendous increase in clinical trial activity. First has been the concerted development of validated outcome measures for EoE. These include symptom, endoscopic and histologic metrics, all of which are important for assessing the efficacy of therapeutics, and many of which have been developed specifically for use in clinical trials and to meet FDA requirements for outcome assessments.  

Second has been the recognition of the opportunities for drug development in EoE. EoE is rapidly increasing in incidence and prevalence at a pace above what would be expected for increased recognition alone. While it is still considered a rare disease, the prevalence in the United States is approximately 1-in-2,000, a frequency that is also seen in Western Europe, South America and Australia, and it accounts for a large healthcare burden of disease - up to $1 billion/year in the U.S. alone. In this context, there is a rapidly expanding set of children and adults who require treatment. Not only are there opportunities to treat more patients, but there are efforts being made to optimize drug delivery to the esophagus in order to maximize clinical, endoscopic and histologic response, to assess response in different clinical phenotypes, to develop agents specifically in children, and to use the expanding knowledge of EoE pathogenesis to develop novel drug targets. All of these efforts can be maximized with active collaboration between academic and industry researchers.

From a personal perspective, it has been both rewarding and educational to be involved in clinical trials related EoE. Because there are no approved medications for EoE, the potential benefits of drug development in this patient population are substantial. In addition, learning about how patient reported outcomes apply to EoE, and how similar measures have been used in other GI diseases such as inflammatory bowel disease and functional GI disorders, has been important. With the focus on patient reported outcomes, and with EoE classified as a rare (orphan) disease, there has also been active collaboration with the FDA. Lessons learned in the drug approval process for other rare diseases can be applied to EoE, and vice versa.

Over the past two decades, EoE has transformed from a case-reportable disease to the second most common cause of esophagitis and the most common cause of food impaction. There has been a tremendous increase in the knowledge about EoE presentation, natural history, epidemiology, treatment response, and pathogenesis. And yet there are major treatment gaps. There are no FDA-approved medications, response rates are sub-optimal, and drugs are not targeted to pathogenesis.

We’ve made impressive progress since the first randomized clinical trial in 2006, and I look forward to seeing where we’ll be in another 10 years.

Evan S. Dellon, MD, MPH, associate professor of medicine and epidemiology, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill

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