What are the indications for Fasenra (benralizumab)?

Indications for Fasenra (Benralizumab)

Fasenra (benralizumab) is FDA-approved for add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma with an eosinophilic phenotype, and for treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). 1

Approved Indications

Severe Eosinophilic Asthma

• Indicated for patients aged 6 years and older
• Must have an eosinophilic phenotype (typically defined as blood eosinophil count ≥300 cells/μL)
• Used as add-on maintenance treatment for patients whose asthma remains uncontrolled despite optimal inhaler therapy with medium-to-high dose inhaled corticosteroids plus long-acting beta-agonists (ICS+LABA) 1, 2
• Particularly beneficial for patients with:
  • History of frequent exacerbations
  • Dependence on oral corticosteroids
  • Poor lung function despite maximal conventional therapy 3

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• Indicated for adult patients with EGPA 1
• Particularly useful for controlling respiratory manifestations of EGPA 4
• Can be considered for patients with relapsing or refractory EGPA without life- or organ-threatening manifestations 4

Mechanism of Action

Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) that:

• Binds to the IL-5 receptor on eosinophils
• Inhibits IL-5 signaling, preventing eosinophil proliferation and survival
• Induces natural killer cell-mediated eosinophil apoptosis, resulting in nearly complete depletion of eosinophils 1, 3

Dosing Regimens

For Severe Eosinophilic Asthma:

• Adults and adolescents ≥12 years:

  • 30 mg subcutaneous injection every 4 weeks for the first 3 doses
  • Then 30 mg every 8 weeks thereafter

• Children 6-11 years:

  • <35 kg: 10 mg subcutaneous injection every 4 weeks for first 3 doses, then every 8 weeks
  • ≥35 kg: 30 mg subcutaneous injection every 4 weeks for first 3 doses, then every 8 weeks 1

For EGPA:

• 30 mg subcutaneous injection every 4 weeks 1

Clinical Benefits

• Significant reduction in annual exacerbation rates (28-36% reduction compared to placebo) 2
• Improvement in lung function (FEV1) 2
• Reduction in asthma symptom scores 2
• Oral corticosteroid-sparing effect in steroid-dependent patients 3, 5
• Long-term safety and efficacy demonstrated for up to 5 years 5
• Rapid and nearly complete depletion of blood eosinophils 3

Important Limitations and Contraindications

• Not indicated for:

  • Relief of acute bronchospasm or status asthmaticus 1
  • Eosinophilic esophagitis (EoE) alone, though it may be considered in patients with coexisting allergic diseases 4

• Contraindicated in:

  • Patients with known hypersensitivity to benralizumab or its excipients 1

Precautions and Monitoring

• Do not abruptly discontinue systemic or inhaled corticosteroids upon initiation of Fasenra; taper gradually if appropriate 1
• Treat pre-existing helminth infections before starting therapy 1
• Monitor for hypersensitivity reactions (anaphylaxis, angioedema, urticaria, rash) 1
• Consider screening for parasitic infections in patients at high risk 1

Emerging Uses (Not Yet FDA-Approved)

• Potential use in Eosinophilic Esophagitis (EoE):

  • Case reports show resolution of dysphagia symptoms and histological evidence of deep remission in patients with both eosinophilic asthma and EoE 4
  • The phase 3 MESSINA trial is evaluating benralizumab in EoE 4
  • Currently not recommended as primary therapy for EoE alone 4

• Hypereosinophilic Disorders:

  • Phase 2 studies show significant lowering of eosinophil count in both serum and tissue 4
  • 74% of patients had sustained response at 48 weeks 4

Practical Considerations

• Convenient dosing schedule (every 8 weeks after initial loading) improves adherence compared to other biologics 3
• Available as prefilled syringe (10 mg/0.5 mL or 30 mg/mL) or autoinjector (30 mg/mL) 1
• Can be self-administered after proper training 1
• Common adverse events include headache, pharyngitis, injection site reactions, and nasopharyngitis 1, 2

Benralizumab represents an important therapeutic option for patients with severe eosinophilic asthma and EGPA, with its unique mechanism of action providing rapid and sustained eosinophil depletion and significant clinical benefits.