A recent study published in The New England Journal of Medicine (NEJM) demonstrates that Fasenra (Benralizumab), an eosinophil-depleting monoclonal antibody, significantly reduces eosinophil counts in patients with Eosinophilic Oesophagitis (EoE), a chronic allergic/immune condition of the oesophagus.

However, the treatment did not show a significant improvement in the severity or frequency of dysphagia symptoms.

What is Eosinophilic Oesophagitis (EoE)?

Eosinophilic Oesophagitis (EoE) is a condition that causes inflammation and scarring of the oesophagus, the tube that connects the mouth to the stomach. EoE can lead to difficulty swallowing, food getting stuck, and chest pain. An allergic reaction to certain foods or environmental factors usually triggers EoE.

The diagnosis and treatment of EoE require repeated endoscopies, which are invasive procedures that involve inserting a camera into the oesophagus and taking tissue samples. Endoscopies can be uncomfortable, expensive, and risky for patients. Therefore, there is a need for alternative methods that can monitor EoE without endoscopies.

Trial Methods

Marc E. Rothenberg, M.D., PhD, from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, and colleagues conducted MESSINA Trial in Phase 3.

This multicentre, double-blind, randomised, placebo-controlled trial included 211 patients aged 12 to 65 with symptomatic and histologically active EoE. Participants were randomly assigned to receive either subcutaneous benralizumab (30 mg) or a placebo every four weeks.

The primary endpoints were histologic response (≤6 eosinophils per high-power field) and changes in the Dysphagia Symptom Questionnaire (DSQ) scores at 24 weeks.

Results

• At week 24, 87.4% of patients treated with benralizumab achieved a histologic response compared to 6.5% in the placebo group.
• There was no significant improvement in dysphagia symptoms.
• Adverse events were comparable between the benralizumab (64.1%) and placebo (61.7%) groups, and no participants discontinued due to adverse events.

Conclusions

This MESSINA trial, funded by AstraZeneca, showed that Benralizumab demonstrated a significant histologic response in EoE patients but did not significantly reduce the severity or frequency of dysphagia symptoms.

What it means for the eosinophilic community

These findings offer a mixed perspective for the eosinophilic community, particularly those affected by EoE. On one hand, the reduction in eosinophil counts indicates a promising step towards managing the inflammatory aspect of the disease. This could potentially prevent long-term tissue damage and improve overall oesophagal health.

However, the lack of improvement in dysphagia symptoms means that patients may continue to experience the primary and most debilitating symptoms of EoE, highlighting an unmet need for symptom relief.

There is a recognised need for more relevant biomarkers to assess clinical response in EoE, as the study shows that reliance solely on eosinophil counts is insufficient. 

Clinicians should rely less on eosinophil levels alone to measure the severity of EoE. Other tests, such as endoscopes and tissue samples collected for microscope analysis, appear more likely to provide meaningful information. Further research on immune responses upstream from Eosinophils is evolving.

Read the full publication

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Learn more about Eosinophilic Diseases beyond eosinophils

Listen to this episode of the Pediatric and Developmental Pathology, hosts Drs. Mike Arnold (@MArnold_PedPath) and Dr. Jason Wang speak with Drs. Nicoleta Arva, Maria Pletneva and Margaret Collins about their work in eosinophilic gastrointestinal disorders with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGiR) and their article in Pediatric and Developmental Pathology: Eosinophilic Gastrointestinal Disorders: A New Path

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Earlier publications and trials on Benralizumab:

Fasenra (benralizumab) vs Nucala (mepolizumab) EGPA management. Phase 3 MANDARA Trial (2024)

The update on Messina Phase 3 Trial (2022)

First UK Patient on Messina Trial (2022)

AstraZeneca and the Division of Intramural Research Phase 2 Trial on EoG (2020)

Beginning of MESSINA Phase 3 trial (2020)