What is the role of Fasenra (benralizumab) in treating Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Role of Fasenra (Benralizumab) in Treating EGPA

Fasenra (benralizumab) can be considered as a treatment option for patients with EGPA who have disease refractory to mepolizumab therapy, particularly for controlling respiratory manifestations and reducing glucocorticoid dependence. 1, 2

Current Treatment Landscape for EGPA

First-Line Therapy

• Glucocorticoids remain the cornerstone of initial therapy for EGPA
• For severe EGPA (FFS ≥1 or organ/life-threatening manifestations): High-dose glucocorticoids plus cyclophosphamide or rituximab 2
• For non-severe EGPA: Glucocorticoids alone or with mepolizumab 2

FDA-Approved Biologic Therapy

• Mepolizumab is currently the only FDA-approved biologic for EGPA
  • Recommended dose: 300 mg subcutaneously every 4 weeks 2
  • Particularly effective for non-severe disease and respiratory manifestations
  • Supported by phase III MIRRA RCT data 1

Benralizumab (Fasenra) in EGPA

FDA Approval Status

• Fasenra is FDA-approved for:
  • Severe eosinophilic asthma (in patients ≥6 years)
  • EGPA in adult patients 3

Dosing for EGPA

• The recommended dosage for EGPA is 30 mg administered subcutaneously once every 4 weeks 3

Evidence for Efficacy

• Multicentre retrospective study (n=68) showed 4:

  • 49% of patients achieved complete response (BVAS=0 and prednisone ≤4mg/day)
  • 36% achieved partial response (BVAS=0 but prednisone >4mg/day)
  • 15% did not respond
  • Glucocorticoids were discontinued in 38% of patients

• Prospective 40-week open-label pilot study (n=10) demonstrated 5:

  • Reduction in median corticosteroid dose from 15mg to 2mg
  • 50% of patients achieved complete steroid discontinuation
  • Reduced annualized exacerbation rate from 4.6 to 1.5 during treatment

Clinical Considerations

When to Consider Benralizumab

1. Patients with EGPA refractory to mepolizumab therapy 1, 2
2. Patients with predominant respiratory manifestations (asthma, ENT involvement) 4
3. Patients requiring high-dose glucocorticoids for disease control 5, 4

Important Caveats

• Efficacy is lower in patients who previously failed mepolizumab therapy (26.7% primary failure rate vs 5.4% in mepolizumab-naïve patients) 4
• Vasculitis flares occurred in 11% of patients on benralizumab, associated with histological evidence of vasculitis and/or ANCA positivity 4
• Rare paradoxical cases of EGPA development during benralizumab treatment have been reported, particularly during oral corticosteroid reduction 6, 7

Practical Approach to Using Benralizumab in EGPA

1. Patient Selection:

   • Consider benralizumab for patients with EGPA who have:
     • Failed or had inadequate response to mepolizumab
     • Predominant respiratory manifestations (severe asthma, ENT involvement)
     • Glucocorticoid dependence

2. Administration:

   • 30 mg subcutaneously every 4 weeks 3
   • Monitor for hypersensitivity reactions after administration

3. Monitoring:

   • Assess disease activity using validated tools (e.g., BVAS)
   • Monitor blood eosinophil counts
   • Evaluate glucocorticoid reduction capability
   • Watch for vasculitis flares, particularly in ANCA-positive patients

4. Optimization of Therapy:

   • Combine with optimized inhaled/topical therapies for respiratory manifestations 1
   • Involve specialists (pulmonologists, otolaryngologists) in management 1

Conclusion

While mepolizumab remains the first-line biologic therapy for EGPA based on stronger evidence, benralizumab represents a valuable alternative for patients with refractory disease, particularly those with predominant respiratory manifestations. The ability of benralizumab to facilitate significant glucocorticoid reduction makes it an important option for improving long-term outcomes and quality of life in EGPA patients.