Before you read on, make sure you’ve checked out Part 1 of our interview, where we discussed what eosinophilic esophagitis is, its symptoms and diagnostic criteria, and why Dr. Dellon chose to study within this field. Today, we’ll discuss Dupixent, research advances, and the future of research.

Research Advances

Since the original discovery and discussion of eosinophilic esophagitis in medical literature, there have been a tremendous amount of research advances. Some of these advances have led to immense benefits. These include the Dupixent approval, as well as the 2018 approval of Jorveza (budesonide orodispersible tablets) in Europe. Jorveza is also available in Canada and Australia.

When asked why research has come so far, Dr. Dellon shares:

“I think it’s a credit to the collaborative and multidisciplinary nature of the field. There are a lot of disciplines studying EoE and looking at fundamental mechanisms of allergies, esophageal barriers, genetic predisposition, risk factors, epidemiology, biomarkers, treatments, outcomes, and population dynamics. Certain research is focused on diagnosis and how to formalize that, how to make it easier for patients. The most gratifying part of the research has been the progression from learning and understanding the condition to learning how to measure it over time, develop treatments and design clinical trials, and ultimately get drugs approved.”

Dupixent: An Overview

Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody which blocks the signaling of two parts of an allergic/inflammatory pathway: interleukin 4 (IL-4) and interleukin 13 (IL-13). It is given as an injectable medication. It is now approved for patients aged 12+ with EoE who weigh more than 88 pounds. Learn more about Dupixent.

Studying Dupixent

Dr. Dellon worked alongside a number of other researchers as a lead investigator in a set of clinical trials determined to understand the safety, tolerability, and efficacy of Dupixent as it related to EoE. He explains that due to Dupixent’s efficaciousness in other similar states, such as asthma, eczema and chronic rhinosinusitis with nasal polyposis, there was a strong rationale that the medicine would work for EoE.

First, a Phase 2 proof-of-concept study enrolled 47 patients. During this study, researchers found that Dupixent was effective in improving swallowing, reduced esophageal inflammation, and healing the esophageal lining.

Next, the research team launched a three-part Phase 3 study to further expand on the data. Eighty-one patients enrolled in the first portion of the study (“Part A”), about half of whom received a placebo and the rest received weekly Dupixent. As Dr. Dellon explains:

This was done to see how well symptoms were improving using a very specific symptom measure. One of the tricky aspects of drug development is how to scientifically show the FDA that people feel better. We used a Patient-Reported Outcome called the Dysphagia Symptom Questionnaire, which patients filled out daily for accurate reporting of whether they were having trouble swallowing on a given day, and if so, how severe the trouble was.

Once the researchers could glean a better idea of how well the trial was going and how patients were responding, they were able to move onto Part B, which tested two different dose frequencies – either every week or every other week. Finally, patients enrolled in Part A and Part B (which lasted about 6 months) were able to move into “Part C”, which allowed extended active treatment for up to one year.

Ultimately, the data that led to the approval was strong and robust, and showed the symptomatic and histologic benefits conferred by Dupixent treatment.

Patient Reactions

When asked how patients reacted to the Dupixent approval, Dr. Dellon highlighted a positive response. While there has been an approved topical steroid formulation for treatment available in other countries since 2018, prior to that and still currently in the United States, doctors had to use it off-label or not provide it at all. So patients and providers were gratified to finally have something approved for US-based patients. In short, this approval was a huge milestone. Dr. Dellon says:

“When I talk to patients, I find it really important to convey to them what the results were and why dupilumab was approved. The study showed that patients who took dupilumab weekly had improved biopsies which were very close to normal, as well as improved symptoms. So I review these data when talking to patients, and also go over where the med can be used.”

“Many people in the study had moderate-to-severe EoE and all of them had failed PPI treatment. Around 70% had tried a topical steroid that wasn’t effective or wasn’t tolerated, and around 40% had an esophageal dilation previously. So this is the group where we know dupilumab was effective, and hopefully this will be studied in other groups, for example those newly diagnosed with EoE, soon. But overall, patients are excited about it.”

The Future of Eosinophilic Esophagitis Research

While Dr. Dellon is happy about the Dupixent approval, he acknowledges that there is still much more research to be done. In the future, he would love to learn more about:

• The best way to use Dupixent long-term
• How the medication works in EoE after more that one year of use
• The right time to begin treatment
• What it would look like to individualize treatment
• How patients whose symptoms were too mild or severe to participate in the study might react to Dupixent

However, he is hopeful at the prospect of how other patient populations could benefit from additional research – and how he himself might be able to play a role in that changing process.