FDA grants priority review to dupilumab for pediatric eosinophilic esophagitis
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Key takeaways:
- Children achieved histological remission for 52 weeks with Dupixent.
- The safety profile was comparable to Dupixent’s use in adolescents and adults.
- The target action date is Jan. 31, 2024.
The FDA has granted priority review to a supplemental biologics license application for dupilumab in the treatment of children aged 1 to 11 years with eosinophilic esophagitis, according to a press release.
Dupilumab (Dupixent; Regeneron Pharmaceuticals, Sanofi) is the first and only treatment that has been approved in the United States to treat EoE in adults and adolescents aged 12 years and older who weigh at least 40 kg. If approved, it also would be the only treatment indicated for younger children with EoE.
“In children, common symptoms of eosinophilic esophagitis include acid reflux, vomiting, abdominal discomfort, trouble swallowing and failure to thrive,” Sanofi and Regeneron told Healio in a statement.
“The debilitating symptoms of this disease can impact growth and development, as well as negatively impact quality of life, including food-related fear and anxiety, which can persist through adulthood,” the statement continued.
Approximately 21,000 children aged younger than 12 years are being treated for EoE in the United States, but about 9,000 of them have not responded satisfactorily to current therapies.
According to the statement, “diet adjustments, which oftentimes includes the elimination of many foods, is the standard treatment for EoE, as well as the use of treatments not approved for the disease.”
These treatments include proton pump inhibitors, swallowed topical corticosteroids or, in severe cases, use of a feeding tube, which may be used to ensure proper caloric intake and weight gain. Potentially, these patients may require biologic therapy instead.
Supporting data
Data from parts A and B of the phase 3 EoE KIDS trial evaluating the efficacy and safety of dupilumab in children with EoE aged 1 to 11 years support the supplemental biologics license application (sBLA). The study is, according to the statement, “the first and only investigational phase 3 trial to show positive results for a medicine for EoE in children this young.”
Part A met its primary endpoint for the proportion of patients who achieved histological disease remission, defined as peak esophageal intraepithelial eosinophil count of six eosinophils or fewer per high power field at 16 weeks for tiered dosing regimens based on body weight compared with placebo.
Specifically, 68% of patients on a higher dose of dupilumab, 58% of those on a lower dose and 3% of those on placebo achieved histological remission (both, P < .0001).
“Children on the higher-dose regimen also experienced significant improvements in abnormal endoscopic findings of their esophagus, with a reduction of 3.5 points compared to an increase of 0.3 points for placebo,” the companies told Healio in the statement.
Part B extended active treatment for 36 more weeks and met the secondary endpoint of maintaining this histologic remission for 52 weeks, in addition to increases in body weight for age percentile, which was an exploratory endpoint in part A and a secondary endpoint in part B.
According to the statement, the companies will report on the full results of Part B at an upcoming conference.
The safety results of both parts of the study were generally consistent with the known safety profile for dupilumab among patients aged 12 years and older who weigh 40 kg or more, the companies reported.
Compared with placebo, adverse events observed among 5% or more of the treatment population included COVID-19, rash, headache, viral gastroenteritis, diarrhea and nausea.
Next steps
Part C of the trial, which is an open-label extension, is ongoing and will evaluate long-term outcomes. All the patients will receive higher exposures to dupilumab at tiered dosing regimens based on body weight without any matching placebo.
The target action date for the FDA’s decision regarding this application is Jan. 31, 2024.
“We are encouraged by the priority review designation provided by the FDA and look forward to working closely with the FDA as they review this sBLA,” the companies said in the statement. “This acceptance brings us one step closer to helping children with EoE between the ages of 1 and 11, and their caregivers, more effectively manage their disease.”
Perspective
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EoE presents as feeding problems, failure to thrive, vomiting and abdominal pain in this age group. It reduces quality of life, including restricted diets and their implications for socialization. Current treatments for EoE in this age group include dietary elimination and medical management through proton pump inhibitors and topical steroids.
Other medicines are not approved for EoE in this age group in the United States, although topical steroids are approved for EoE in Europe and other select regions. The availability of medicine available following FDA approval will bring needed care to this patient group.
As one of the trial investigators and one of the primary scientists researching EoE outside of the companies involved in the data analysis and communication, I am optimistic about this treatment. The study met its primary and many other outcome measures and proved to be safe. I expect it to be approved. It is gratifying to see therapy emerging for EoE and that children are not a forgotten population.
It is not a light matter to treat children in the age range, including babies, with an injectable biological agent, so I am pleased to see the extensive data package and positive results.
Perspective
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EoE has a significant impact on quality of life in children. Failure to thrive, food refusal and adaptive eating behaviors are common findings. The symptoms of dysphagia that are most common in older children, adolescents and adults are less commonly seen in younger children. Symptoms often present with vomiting and abdominal discomfort, making a diagnosis of EoE difficult in the early years of life.
Current therapeutic options include pharmacological management and/or elimination diets. Elimination diets are particularly challenging in younger children. They are often not willing to eliminate the foods most often associated with EoE, including dairy and wheat. To ensure adequate nutrition in an elimination diet, the help of a dietitian is often required. However, access to dietitians who are experts in the management of food allergies and EoE elimination diets is limited. This leaves most providers and parents relying on the internet or support organizations for guidance.
Pharmacological therapy currently includes proton pump inhibitors and swallowed corticosteroids, but neither has been approved by the FDA for treating EoE. Although it is generally safe and effective, parents are often hesitant to use chronic medical therapy. Also, young children often refuse the medications. As with all medications in children, ensuring adherence is always problematic.
Dupilumab would be an effective alternative in children who fail traditional therapy. Even though proton pump inhibitors and swallowed corticosteroids are not approved for the treatment of EoE, their use is widespread, effective and generally considered safe. Therefore, dupilumab should probably be reserved for those children who have failed conventional therapy.
The drug application in this study was from ages 1 to 11 years. We know this medication is effective and safe in children aged as young as 6 months with severe atopic dermatitis. But for children aged younger than 6 years, diagnosing, treating and understanding the chronicity of EoE is more difficult than it is for adolescents and adults. Initiation of biological therapy in this age group, although effective, would require significant shared decision-making between the family and the provider.
Research needs to focus on how foods play a role in EoE in young children. Is the natural disease course in children similar to adults, suggesting a chronic and progressive disease from the onset even at a young age? Research also should determine whether there is spontaneous resolution over time in younger children.
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