What is the current status of Tezspire (tezepelumab) in clinical trials for asthma and Chronic Obstructive Pulmonary Disease (COPD)?

Current Clinical Trials of Tezspire (Tezepelumab) for Asthma and COPD

Tezepelumab (Tezspire) has shown significant efficacy in severe, uncontrolled asthma across multiple clinical trials, but recent phase 2a trials for COPD did not meet their primary endpoint, though promising results were seen in patients with higher blood eosinophil counts.

Tezspire in Asthma: Established Efficacy

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), a key cytokine in the inflammatory cascade. The FDA has approved Tezspire for severe asthma based on robust clinical evidence:

• PATHWAY (Phase 2b): 52-week trial showing significant reduction in exacerbations in adults with severe asthma 1
• NAVIGATOR (Phase 3): 52-week pivotal trial demonstrating 56% reduction in annualized asthma exacerbation rate compared to placebo 1
• DESTINATION (Extension Study): Long-term safety and efficacy study showing sustained benefits over 104 weeks with favorable safety profile 2

Key findings from these asthma trials:

• Tezepelumab reduced exacerbations regardless of baseline blood eosinophil counts or FeNO levels 1, 3
• Significant improvements in FEV1 were observed as early as 2 weeks after treatment initiation 1
• Improvements in patient-reported outcomes including ACQ-6 and AQLQ(S)+12 scores 1
• The drug was well-tolerated with safety profiles similar to placebo 2

Tezspire in COPD: Emerging Evidence

The most recent and significant trial for COPD is the COURSE study:

• COURSE (Phase 2a): Randomized, placebo-controlled trial evaluating tezepelumab 420mg Q4W in moderate to very severe COPD 4
• Primary endpoint not met: Annualized rate of moderate/severe COPD exacerbations was 1.75 for tezepelumab versus 2.11 for placebo (rate ratio 0.83, p=0.10) 4
• Promising subgroup findings: Patients with higher baseline blood eosinophil counts showed better responses:
  • BEC <150 cells/μL: No benefit (rate ratio 1.19)
  • BEC 150-300 cells/μL: 34% reduction in exacerbations (rate ratio 0.66)
  • BEC ≥300 cells/μL: 46% reduction in exacerbations (rate ratio 0.54) 4

Current Treatment Landscape for COPD

Current COPD management focuses on:

1. Bronchodilators: LAMA+LABA combinations form the foundation of pharmacological treatment 5, 6
2. Anti-inflammatory therapy: ICS added for patients with high blood eosinophil counts or history of asthma 5, 6
3. PDE4 inhibitors: For patients with chronic bronchitis and severe to very severe COPD 5
4. Macrolide antibiotics: Long-term azithromycin may reduce exacerbations but increases bacterial resistance 5

Future Directions for Tezepelumab in COPD

Despite not meeting the primary endpoint in COURSE, the eosinophil-stratified results suggest potential for tezepelumab in specific COPD phenotypes:

• Eosinophilic COPD: The stronger response in patients with higher blood eosinophil counts suggests a potential role in this phenotype 4
• Overlap with asthma: Given its efficacy in severe asthma, patients with asthma-COPD overlap may benefit

Ongoing and Planned Research

While no new COPD trials for tezepelumab are currently registered, the COURSE results suggest future studies should:

1. Focus on patients with higher blood eosinophil counts (≥150 cells/μL)
2. Potentially explore higher dosing (the COPD trial used 420mg vs 210mg in asthma)
3. Investigate biomarkers beyond blood eosinophils to identify responders

Clinical Implications

For clinicians considering biologic therapies:

• For severe asthma: Tezepelumab is FDA-approved and effective regardless of T2 biomarker status
• For COPD: Current evidence does not support routine use of tezepelumab
• For eosinophilic COPD: Consider enrollment in clinical trials if available, as this subgroup showed promising signals

Conclusion

Tezepelumab has established efficacy in severe asthma across multiple phenotypes. For COPD, while the primary endpoint was not met in the COURSE trial, the subgroup analysis suggests potential benefit in patients with higher blood eosinophil counts. Further studies are needed to determine if tezepelumab could benefit specific COPD phenotypes.