Eosinophilic esophagitis (EoE) is a rare, progressive, chronic inflammatory disease of the esophagus currently believed to be characterised by the abnormal presence of eosinophils, a type of white blood cell, in the inner lining of the esophagus.1-3 Patients experience difficulty with swallowing (dysphagia), pain, food getting stuck and anxiety.4,5
High-level results from the
In the trial, histological disease remission was measured as theproportion of patients with less than or equal to six eosinophils per high power field at Week 24. Burden of dysphagia was assessed using the patient-reported Dysphagia Symptom Questionnaire (DSQ) and measured as a mean change from baseline at Week 24. The trial included 210 patients, who received either Fasenra or placebo at four-week intervals.
The safety and tolerability profile for Fasenra in the trial was consistent with the known profile of the medicine.
Results from
Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU,
Notes
The dual-primary endpoints analysed at Week 24 were the proportion of patients with a histologic response, defined as a peak esophageal eosinophil count less than or equal to 6 eosinophils per high power field, and mean changes from baseline in Dysphagia Symptom Questionnaire (DSQ).8 The peak eosinophil count is obtained when a biopsy of the tissue of the esophagus is examined under a microscope. The histologic response endpoint used in the trial is consistent with histologic remission.10 The DSQ captures the presence and severity of dysphagia symptoms in the past day in a 4-item patient-reported questionnaire and the score is calculated over 14-day periods, ranging from 0 to 84, with a lower score indicating less severe dysphagia.8
The trial period consists of a 24-week double-blind, placebo-controlled treatment period followed by a 28-week open-label treatment period.8 Eligible patients were randomised in a 1:1 ratio to receive either 30 mg of Fasenra or placebo at 4-week intervals for the double-blind period. Patients who complete the double-blind period on Fasenra continue into the open-label treatment period with all patients receiving Fasenra 30 mg at 4-week intervals until Week 52, with a further open-label extension offered to eligible patients thereafter.9
In the trial, patients were allowed to remain on background medications for EoE, including proton pump inhibitors, topical corticosteroids, and EoE-driven diet elimination, provided that they were stable prior to entry and during the first 52 weeks of treatment, unless changes were clinically indicated.8,9
Fasenra
Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).11
Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU,
Fasenra is in development for other eosinophilic diseases including bullous pemphigoid, chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria, eosinophilic esophagitis, eosinophilic gastritis/eosinophilic gastroenteritis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome and non-cystic fibrosis bronchiectasis.
Fasenra was developed by
Respiratory & Immunology, part of BioPharmaceuticals, is one of
With common pathways and underlying disease drivers across respiratory and immunology,
Contacts
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References
1. Muir A, et al. Eosinophilic Esophagitis: A Review. JAMA. 2021;326:1310-1318.
2. Dellon ES, et al. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018;154:319-332.e3.
3. Cheng E, et al. Tissue remodeling in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol. 2012;303:G1175-G1187.
4. Hirano I, et al. Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis. Gastroenterol Clin North Am. 2014;43:297-316.
5. Lucendo AJ, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5:335-358.
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8. Clinicaltrials.gov. A Study of Benralizumab in Patients With Eosinophilic Esophagitis (
9. AstraZeneca Data on file. 2022 - REF-162311.
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12. Bleecker ER, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ? 2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.
13. FitzGerald JM, et al. Benralizumab, an anti-interleukin-5 receptor ? monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.
14. Nair P, et al. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017;376:2448-2458.
15. Menzies-Gow A, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10:47-58.
16. Harrison TW, et al. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial. Lancet Respir Med. 2021;9:260-274.
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