What biologic therapies are available for patients with severe Chronic Obstructive Pulmonary Disease (COPD)?

Biologic Therapies for Severe COPD

Currently, there are no FDA-approved biologic therapies specifically indicated for routine treatment of severe COPD, with mepolizumab being the only biologic showing promising results in patients with an eosinophilic phenotype of COPD.

Current Treatment Landscape for Severe COPD

The management of severe COPD primarily relies on conventional pharmacological treatments:

First-Line Treatments

• Long-acting bronchodilators: LAMA and/or LABA as maintenance therapy 1
• Triple therapy: LAMA/LABA/ICS for patients with persistent symptoms and frequent exacerbations 2, 1

Anti-inflammatory Options

• Phosphodiesterase-4 (PDE4) inhibitors: Roflumilast is the only approved anti-inflammatory medication specifically for severe COPD 2, 3
  • Indicated for patients with chronic bronchitis, severe to very severe COPD, and history of exacerbations
  • Reduces moderate and severe exacerbations
  • Common side effects include diarrhea, nausea, reduced appetite, weight loss, and headache

Macrolide Antibiotics

• Long-term azithromycin or erythromycin: Reduces exacerbations over 1 year in selected patients 2
  • Associated with increased bacterial resistance and hearing impairment

Emerging Biologic Therapies

Mepolizumab

• Mechanism: Monoclonal antibody targeting interleukin-5, which mediates eosinophilic inflammation 4, 5
• Evidence:
  • The MATINEE trial (2025) demonstrated that mepolizumab 100mg subcutaneously every 4 weeks significantly reduced moderate or severe exacerbations compared to placebo (0.80 vs 1.01 events per year; rate ratio 0.79) in patients with blood eosinophil counts ≥300 cells/μL 5
  • Earlier METREX and METREO trials (2017) showed similar benefits in patients with eosinophilic phenotype 4
• Patient selection: Only effective in the subset of COPD patients with eosinophilic phenotype (approximately 20-40% of COPD patients) 6
• Current status: Not yet FDA-approved specifically for COPD but showing promising results

Other Biologics Under Investigation

• Several biologics targeting different inflammatory pathways are in various stages of clinical development 6, 7
• These include agents targeting:
  • Leukotriene B4 inhibitors
  • Other inflammatory cytokines
  • None have yet demonstrated sufficient efficacy to achieve regulatory approval

Clinical Approach to Biologic Therapy in COPD

1. Identify potential candidates:

   • Patients with severe COPD (FEV1 <50% predicted)
   • Frequent exacerbations despite optimal inhaled therapy
   • Blood eosinophil count ≥300 cells/μL

2. Optimize conventional therapy first:

   • Ensure adherence to triple therapy (LAMA/LABA/ICS)
   • Consider roflumilast for patients with chronic bronchitis phenotype 2, 3
   • Consider macrolide therapy for frequent exacerbators 2

3. Consider mepolizumab for appropriate candidates:

   • Only for patients with confirmed eosinophilic phenotype
   • May be considered in clinical trials or off-label use after discussion of limited evidence base

Practical Considerations

• Cost and access: Biologics are expensive and may not be covered by insurance for COPD
• Administration: Requires regular subcutaneous injections (typically every 4 weeks)
• Monitoring: Regular assessment of exacerbation frequency, symptoms, and lung function to determine efficacy

Key Caveats

• The field of biologics in COPD is still evolving, with limited approved options
• Patient selection is critical - only those with specific inflammatory phenotypes are likely to benefit
• Conventional therapies remain the foundation of COPD management
• Mepolizumab shows the most promise but primarily in the subset of patients with eosinophilic COPD

The development of biologics for COPD represents an important step toward precision medicine in this heterogeneous disease, but currently remains limited to specific phenotypes with eosinophilic inflammation.