What is the dose and indications for Benralizumab (anti-interleukin-5 receptor alpha subunit monoclonal antibody)?

Benralizumab Dosing and Indications

Benralizumab is primarily indicated for severe eosinophilic asthma at a dose of 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter, with weight-based dosing for children 6-11 years (10 mg for <35 kg, 30 mg for ≥35 kg). 1

Approved Indications

• Severe Eosinophilic Asthma: Benralizumab is FDA-approved as add-on maintenance treatment for patients with severe asthma aged 6 years and older with an eosinophilic phenotype 1
• Eosinophilic Granulomatosis with Polyangiitis (EGPA): Indicated for adult patients with EGPA, particularly for those with refractory asthma/ENT disease without systemic manifestations despite high-dose glucocorticoids and optimized inhaled therapy 2

Dosing Regimen

For Asthma:

• Adults and adolescents ≥12 years: 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter 1
• Children 6-11 years:
  • 10 mg subcutaneously for patients <35 kg 1, 3
  • 30 mg subcutaneously for patients ≥35 kg 1, 3
  • Same frequency as adults (every 4 weeks for first 3 doses, then every 8 weeks) 1

For EGPA:

• 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter 2

Mechanism of Action

• Benralizumab is a humanized, afucosylated monoclonal antibody that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) 1
• It depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity 4
• This mechanism differs from other anti-IL-5 agents like mepolizumab, which target the IL-5 ligand rather than the receptor 5

Clinical Efficacy

• In severe eosinophilic asthma, benralizumab demonstrated:
  • 72.8% reduction in annualized exacerbation rate in real-world studies 6
  • Significant reduction in maintenance oral corticosteroid use, with 51.4% of patients able to discontinue oral steroids completely 6
  • Improved lung function and quality of life measures 6, 7
• Most effective in patients with blood eosinophil counts ≥300 cells/μL 5
• In Japanese patients with severe eosinophilic asthma, benralizumab reduced annual exacerbation rates by 66-83% 7

Off-Label Uses Under Investigation

• Eosinophilic Esophagitis (EoE): Cases reported of complete resolution of dysphagia symptoms and histological evidence of deep remission in patients with both eosinophilic asthma and EoE 2
• Hypereosinophilic Disorders: A phase-2 study showed significant lowering of eosinophil count in both serum and tissue, with 74% of patients having sustained response at 48 weeks 2
• Allergic Bronchopulmonary Aspergillosis (ABPA): Recommended as an option for managing treatment-dependent ABPA 2
• Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Potential candidate for management based on efficacy in eosinophilic asthma 2

Monitoring and Safety

• Therapeutic drug monitoring is recommended when using benralizumab 2
• Common adverse events include:
  • Nasopharyngitis (11% vs 6% placebo) 5
  • Injection site reactions (16% vs 4% placebo) 5
• Safety profile in children 6-11 years is similar to that observed in adults and adolescents 1, 3
• Lack of response may be associated with chronic airway infection or development of anti-drug antibodies 6

Important Considerations

• Benralizumab has not been approved for EoE alone, but may be a treatment option in patients with coexisting allergic diseases 2
• The MESSINA phase 3 trial is evaluating benralizumab in EoE patients 2
• For patients with EGPA, benralizumab can be considered when disease is refractory to mepolizumab therapy 2
• In pediatric patients, efficacy is extrapolated from adult and adolescent trials with supporting pharmacokinetic and pharmacodynamic data 1

Contraindications and Special Populations

• Safety and effectiveness in EGPA patients younger than 18 years have not been established 1
• No overall differences in safety or effectiveness were observed in geriatric patients compared to younger patients 1
• If benralizumab is transferred into human milk, the effects on the breastfed infant are unknown 1