New Treatment Gives Hope to Those with EoE

New Treatment Gives Hope to Those with EoE

Experts at Cincinnati Children’s are savoring the news that the U.S. Food and Drug Administration (FDA) approved Dupixent (dupilumab) on May 20, 2022, as the first treatment for eosinophilic esophagitis (EoE), a chronic, allergic inflammatory disease.

About 160,000 people in the United States have EoE, which occurs when a type of white blood cell, the eosinophil, collects in the esophagus. This elevated number of eosinophils can release substances into surrounding tissues that cause injury and inflammation to the esophagus.

People with EoE can have painful choking experiences when trying to swallow even small amounts of food. Managing the condition often involves following highly restrictive diets, with some relying on feeding tubes. Until now, people have received various therapies in clinical trials and off-label uses of drugs approved for other conditions.

Dupilumab is a monoclonal antibody that helps inhibit the inflammation associated with EoE. The therapy is now approved for use in adults and pediatric patients 12 years and older who weigh at least 88 pounds.

Approval a Milestone in 20-Year Research Quest

“This is a victory for science, patients, rare diseases and advocacy,” said Marc Rothenberg, MD, PhD, director of the Cincinnati Center for Eosinophilic Diseases (CCED) at Cincinnati Children’s. Rothenberg has been researching EoE for the past two decades and has played an essential role in dupilumab’s development for EoE.

“Developing a drug takes a village, and that village is Cincinnati Children’s, a great place that comes together to make something like this happen,” said Rothenberg. “Cincinnati Children’s really provides the environment to optimize probability of success and to think about medical problems holistically to make sure that we’re looking at the right areas and leveraging the strengths of the hospital, including its excellent people.” As an example of this holistic approach, Margaret Collins, MD, director of Gastrointestinal Pathology, who works with Rothenberg as a researcher, explains, “The studies from Marc’s lab provided the basis for testing Dupixent to treat EoE. I recall the day Jennifer Davidson Hamilton, PhD, from Regeneron Pharmaceuticals, and I decided that the pathology research core would process the biopsies and I would score the slides using our not-yet-published eosinophilic esophagitis histology scoring system. Anatomic pathologists do not commonly work directly with pharmaceutical companies, but Cincinnati Children’s advances relationships that facilitate our goal of changing the outcome together. I am honored to have had these opportunities and in awe of the generosity of the patients who participate in clinical trials.” Early on, EoE was not well-understood. In 1999, Rothenberg, Collins, Phil Putnam, MD, director, Endoscopy Services, and a team of researchers started exploring and forming ideas about this condition. This combination of expertise in pediatric allergy, gastroenterology, and pathology was powerful. “I was mainly interested in the research of the disease, and they were interested more in the clinical aspects, but over the years, we really started to change the way people thought about this process that nobody knew a lot about,” Rothenberg says.

(L-r) Philip Putnam, MD; Marc Rothenberg, MD, PhD; Kara Kliewer, RD, PhD; Julie Daisey, MS. Says Steve Davis, MD, MH, president and CEO, "Marc and his team are an example of what Cincinnati Children’s is all about. We come together to provide great care for kids and to have brilliant researchers looking at how to make tomorrow better for kids. Children and adults with EoE are going to have a better tomorrow because of the work that Marc and his team has put in over the years.”

Rothenberg with a patient, Aiden.

Some thought EoE might be related to acid reflux disease. However, studies by Rothenberg and his team demonstrated that EoE was the result of an allergic response to food, involving a protein, interleukin (IL-13), that stimulates cells to release eosinophil attractants.

Rothenberg and his team conducted proof-of-principle studies, initially in pre-clinical systems and then in patients, which provided the scientific rationale and proof for using dupilumab to treat patients with EoE. The therapy works by blocking the binding of IL-13 and a related protein (interleukin 4) to its receptor, which restricts activation of the allergic arm of the immune system.

“This is a pretty incredible moment,” said Steve Davis, MD, president and CEO. “The development of the FDA-approved drug dupilumab by Marc Rothenberg and his amazing laboratory team is something that can only happen at a place like Cincinnati Children’s. The combination of a brilliant investigator with persistence and resilience over the number of years, great collaborators and the facilities, and the team that came together to make this happen, really is something that we—as an organization—should be incredibly proud of.”

Noted Putnam, “We’re indebted to Marc and his incomparable team for all the basic science research they have done, but I also want to recognize the institutional and divisional support we’ve received. Patients are cared for collaboratively with the allergists and with the dedication of our nurses, dietitians, and psychologists. We’re able to provide clinical care in addition to the research side of things, which has been crucial. We’re also totally indebted to our patients who come here for clinical care but then decide to participate in research, which makes all the clinical trials relevant, and in this case, successful.”

Rothenberg continues to lead studies of EoE and related conditions as founder and director of the Rothenberg CURED Lab and the CCED at Cincinnati Children’s. He is also the principal investigator of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), which is part of the NIH-funded Rare Diseases Clinical Research Network (RDCRN). Investigators in CEGIR’s national network of 20 clinical sites have worked collaboratively to generate and refine several tools that support the clinical trial process. These tools, which measure disease severity and treatment efficacy, include collecting patient-reported outcomes, endoscopic reference scores, a histologic scoring system, and an EoE diagnostic panel.

Next Steps

Cincinnati Children’s follows and studies data from more than 2,500 patients from across the United States who suffer from eosinophilic disease. The new treatment will be available at Cincinnati Children’s, and Rothenberg predicts usage will grow soon.

“This treatment will benefit about one-third of the current 160,000 people diagnosed in the United States. However, most patients are not yet using it,” Rothenberg says.

Adding to the excitement: This news arrived just in time to finish out National Eosinophil Awareness Week.

Highlights of a Long Journey

The timeline shows major advances and achievements from the Rothenberg CURED Lab and Cincinnati Center for Eosinophilic Disorders (CCED) that formed the basis for the FDA’s approval of dupilumab.

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