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We sat down with Evan Dellon, MD, MPH, to discuss the use of dupilumab in pediatric EoE patients, with the agent gaining FDA approval as the first and only indication for this patient population on January 25, 2024.
The US Food and Drug Administration (FDA) has approved dupilumab (Dupixent) for the treatment of eosinophilic esophagitis (EoE) in pediatric patients 1-11 years of age weighing ≥ 15 kg, making it the first and only FDA-approved medicine specifically indicated for this patient population.1
Announced by Sanofi on January 25, 2024, this approval expands the previous FDA decision for dupilumab in adult and pediatric patients 12 years and older weighing ≥ 40 kg in May of 2022, when it became the first and only medicine specifically indicated to treat EoE in the United States.1,2
A fully human monoclonal antibody, dupilumab inhibits the signaling of interleukin-4 and interleukin-13 pathways and has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 trials.3
Regeneron Pharmaceuticals announced the US Food and Drug Administration (FDA) accepted their supplemental Biologics License Application for dupilumab in pediatric EoE patients on September 26, 2023, citing an anticipated target action date for the FDA decision of January 31, 2024.3
The newest FDA approval comes ahead of the previously reported target action date and is based on data from the phase 3 EoE KIDS trial with 2 parts evaluating the efficacy and safety of dupilumab in children 1-11 years of age with EoE. At 16 weeks, 66% of children who received higher dose dupilumab at tiered dosing regimens based on weight achieved histological disease remission (≤6 eosinophils/high power field), the study’s primary endpoint, compared to 3% for placebo.1
Of note, histological remission was sustained at week 52, with 53% of children treated with dupilumab in Parts A and B. Histological remission was also achieved at week 52 in 53% of children who switched to dupilumab from placebo in Part B.1
According to the release, the safety profile of dupilumab through 16 weeks in children aged 1-11 years was generally similar to that observed through 24 weeks in adult and pediatric patients aged ≥ 12 years. The most common adverse events (≥2%) more frequently observed with dupilumab than placebo were injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections, with a single case of helminth infection reported in the dupilumab arm of EoE KIDS Part B.1
For more insight into how the approval of dupilumab might impact treatment algorithms and the management of pediatric patients with EoE, check out our Q&A with Evan Dellon, MD, MPH, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina Chapel Hill.
Editors' note: this interview took place on January 25, 2024, prior to the approval of dupilumab.
HCPLive: Can you explain the unmet need in this patient population of children with EoE and why this pipeline development is warranted?
Dellon: So, the short answer is we don't have any approved medications for EoE in children. Actually, nowhere in the world are there any approved medications for them and the prior approval for dupilumab only went down to those 12 years of age. Right now, children can use off-label proton pump inhibitors, off-label topical steroids, or dietary elimination therapy, but all of them are really suboptimal and have challenges—either for adherence or even in just obtaining from insurances. So, it's really critical that medications are developed for the pediatric population and in particular these youngest kids who are quite affected with symptoms, growth and development, and nutritional problems from EoE.
HCPLive: What exactly would dupilumab contribute to this patient population as a treatment option?
Dellon: Assuming that kids in this age range can get and tolerate the current therapies, we often see response rates of 30-40% or more, regardless of the different kinds of treatments. For example, PPI nonresponse rates may be as high as 50, 60, or 70%. With topical steroids, we usually have about a 30-40% nonresponse rate. With diet, it could be 50% or more depending on the type of diet.
So, even with the current treatments, for kids who are not responding well, may be having side effects with different treatments, or having trouble taking them, I think it could really give us a nice option as a potentially approved medication.
HCPLive: Are there any hurdles to optimal uptake you could foresee?
Dellon: I think there are some hurdles that can be overcome with education. So, for example, this is a biologic medication that has a good safety profile and is not as immunosuppressant as maybe some biologics. We still don't know the dosing or the frequency yet, but it is an injection—so, that may be a hurdle. Again, that's overcome by these families and some of these families, for kids with food allergies, may be familiar with other injectables, such as Epipens or asthma with other biologics that are on the market.
I think the logistic hurdles, especially upfront, may just end up being insurance and cost.— I think we're still seeing a lot of those hurdles on the adult side as well.
Another hurdle is that the clinical trial population is a very selected group. So, from a provider standpoint, understanding if the medication is appropriate for the patient in front of them given their history is also something that is going to have to be thought about, but that isn't necessarily a traditional kind of a hurdle.
Editors' note: Following the approval of dupilumab for treatment of EoE in pediatric patients 1-11 years of age weighing ≥15 kg, the recommended dosage of dupilumab for adult and pediatric patients ≥ 1 year of age, weighing ≥15 kg, is as follows: 15 to < 30 kg: 200 mg every other week (Q2W); 30 to < 40 kg: 300 mg every other week (Q2W); ≥40 kg or more: 300 mg every week (QW).
HCPLive: Based on the data, could you see this becoming a first-line option for pediatric EoE?
Dellon: I think this kind of medicine is a no-brainer for the patients who are not responding to other kinds of treatments. So, that's really, I think, where it's going to be used most naturally.
I think the other places that it could be used naturally, and there is some early guidance on this in adults as well as adolescents, but for kids who have multiple atopic conditions. Of course, if their asthma or eczema may be severe enough to use dupilumab for that indication. Additionally, when there is a child who is on multiple steroid medicines for multiple atopic conditions and there are concerns about growth or something to that extent.
I think what we don't know is whether patients who are just newly diagnosed, can use this and how much it'll benefit the other patients in the pediatric study, as well as in the adults study, who were not newly diagnosed. These patients were all unresponsive to PPI. So, I think that's something that I'm hoping will be developed more in the future. In terms of can it be a first line option and can we make the analogy that we do with inflammatory bowel disease that we want to use it upfront in the most severe patients? I think we need a little bit more data to support those kinds of decisions just now.
1. Fitch, J. FDA approves dupilumab for eosinophilic esophagitis in children aged 1 to 11 years. Contemporary Pediatrics. January 25, 2024. Accessed January 25, 2024. https://www.contemporarypediatrics.com/view/fda-approves-dupilumab-for-eosinophilic-esophagitis-in-children-aged-1-to-11-years
2. Butera, A. FDA Approves Dupilumab for Eosinophilic Esophagitis. HCPLive. May 20, 2022. Accessed January 25, 2024.
3. Brooks, A. FDA Accepts Priority Review Application for Dupilumab for Pediatric Eosinophilic Esophagitis. HCPLive. September 26, 2023. Accessed January 25, 2024. https://www.hcplive.com/view/fda-accepts-priority-review-application-for-dupilumab-for-pediatric-eosinophilic-esophagitis