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Two Studies Show Mixed Progress Against EoE

2024-06-26

临床3期上市批准临床结果

Experts at Cincinnati Children's play key roles in one trial that supports dupilumab use for children under 12 and another study showing no relief for people taking benralizumab.

Both studies appear in The New England Journal of Medicine.

CINCINNATI, June 26, 2024 /PRNewswire/ -- Despite high hopes, a drug that wipes out the namesake cell type associated with the disease eosinophilic esophagitis (EoE) doesn't make patients feel better and doesn't reverse tissue damage in their throats.

Meanwhile, data show that a different drug that had previously been approved for use in adults and teens with EoE is also safe and effective for children under 12 who weigh at least 15 kg (about 33 pounds).

While approval for dupilumab has been approved for children under 12, benralizumab shows no benefit to patients with EoE, according to results from two clinical trials published in the New England Journal of Medicine.

The results of thesdupilumabl trials—plus an accompanying editorial—apbenralizumabJune 17, 2024, edition of The New EEoEand Journal of Medicine.

"Together, these trials provide exciting advances in our understanding of, and treatment options for, this increasingly common and perplexing disease," writes Benjamin Wright, MD, an allergist-immunologist with The Mayo Clinic in Phoenix, AZ.

Long-time EoE expert Marc Rothenberg, MD, PhD, and colleagues at Cincinnati Children's were deeply involved in both studies.Mayo Clinic

What is EoE?Cincinnati Children's

This sevEoE form of food allergy occurs in an estimated 180,000 people in the United States, including at least 21,000 children under 11. For those affected, a variety of foods can trigger a powerful immune response. Patients can experience painful throat inflammation, tissue damage, and difficulty swallowing. When not controlled, the ongoing disruption to a healthy diet can limit a child's growth and lead to other complications.

The most distinguishfood allergyof EoE has been a well-documented spike in the number of eosinophils – a type of white blood cell – found in the throat. For many years this surge of immune cells also was believed to be the primary cause of tpainful throat inflammation

New findings from the Phase 3 MESSIEoEclinical trial add to a body of evidence suggesting otherwise.

Effective but not helpful

This study evaluated a monoclonal antibody treatment called benralizumab, which has been shown in other studies to be highly effective at reducing unwanted eosinophils. Somewhat like an exploding paint capsule making it easier for cops to catch a bank robber, the antibody binds to eosinophil cells and exposes them to patrolling natural killer cells.

In fact, this treatment has been approved for treating poorlbenralizumab asthma because it helps break a feedback cycle of eosinophil-mediated hyperreaction and mucus production in inflamed airways. That asthma success inspired many scientists to hope that benralizumab would become a difference-maker in treating EoE.

But when tested in 211 patients with EoE—ages 12 to 65—people still experasthma inflammation, difficulty swallowing, pain, and reduced quality of life. This occurred despite more than 80% of those taking asthmaizumab showing "near-complete depletion" of eosbenralizumabtheir blood and esophagus. Further, microscopEoEexams of tissue samples showed no significant improvement at a biological level.

"This trial calls into question the cEoEical relevance of monitoring EoE for treinflammationt difficulty swallowingf paindegree of eosinophilic inflammation," says Rothenberg. "The MESSINA study highlightbenralizumabance of research as it was a very reasonable assumption that eosinophilic esophagitis would be caused by eosinophils. Based on these new results, we now know that this assumption is primarily incorrect."

Rothenberg, who directs the Division of Allergy and Immunology at CinEoEnati Children's, served as corresponding author for the stueosinophilic inflammation with the University of North Carolina at Chapel Hill, was co-first author.eosinophilic esophagitis

Extended approval for dupilumabAllergy University of North Carolina at Chapel Hill

Benralizumab targets tdupilumabty of interleukin-5 (one of several proteins involved in our bodies' immune response). But other research has shown better results against EoE by targeting two other interleukins at the same time: IL-4 and IL-13.

Benralizumaband Drug Administration iinterleukin-5oved the drug dupilumab for treating EoE in 2022, but only for adults and teens. Based on data from a more recent clinicEoEtrial focusing on younger children, the FDA acted in JaIL-4y 202IL-13extend approval to children aged 1 to 12 who weigh at least 15 kg (about 33 pounds).

The datFood and Drug Administrationsupported that decision also dupilumabished in NEJM EoEJune 27.FDA

To date, dupilumab is the only FDA-approved medication that precisely treats EoE in children.

Years of dupilumabproducing resultsEoE

Rothenberg and Margaret Collins, MD, Division of Pathology and Laboratory Medicine at Cincinnati Children's, were co-authors on both studies published in the NEJM. They have been studying EoE for decades and have been active since the early days in evaluating both drugs.

Julie Caldwell, PhD, Division of Allergy and Immunology at Cincinnati Children's, was a co-author on the benralizumab study.EoE

What's next for doctors, researchers and people with EoE?benralizumab

In the short term, Rothenberg says that patients shouEoEconsider dupilumab, but not benralizumab, or continue (or return to) other treatments that have been helpful. Dietary elimination therapy to avoid offending food triggers has been used for years but can be tough to follow. Various medications have helped some patients manage symptoms, including proton-pump inhibitors and steroid treatments. A few newer approaches are still being studied in other clinical trials.

Longer term, Rothenberg and other scientists are looking farther dupilumab" from eosbenralizumabthe body's natural cascade of immune system responses to find other ways to stop, slow, or prevent the damage caused by EoE.proton-pump inhibitors proton-pump steroid

Until such work produces new options, Rothenberg also recommends that clinicians rely less upon eosinophil levels as the sole feature to gauge the severity of EoE. Other tests such as endoscope exams and collecting tEoEue samples for microscope analysis appear more likely to provide meaningful information.

"We need a more relevant biomarker to measure clinical response in eosinophilic esophagitis," Rothenberg says. "That is certainly one of our main research goalEoEs we move forward."

About these studieseosinophilic esophagitis

The MESSINA clinical trial was supported by AstraZenica. The dupilumab clinical trial was supported by Sanofi and Regeneron Pharmaceuticals.

SOURCE Cincinnati Children's Hospital MedicaAstraZenica dupilumab Sanofi Regeneron Pharmaceuticals