Benralizumab fails to cut COPD exacerbations in phase 3 trials

  • Criner GJ & al.
  • N Engl J Med
  • 12.09.2019

  • von Miriam Davis, PhD
  • Clinical Essentials
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Takeaway

  • Add-on benralizumab, an interleukin-5 receptor α-directed cytolytic monoclonal antibody, failed to prevent COPD exacerbations in the GALATHEA and TERRANOVA phase 3 randomized placebo-controlled trials.

Why this matters

  • Episodes of moderate (resulting in enhanced treatment) and severe (resulting in hospitalization) exacerbations adversely affect patients' health and prognosis and carry high economic costs.

Study design

  • GALATHEA (n=1120) and TERRANOVA (n=1545) were 56-week studies of add-on benralizumab vs placebo in patients with moderate to severe COPD and frequent exacerbations despite receiving guideline-based inhaled treatment.
  • Primary outcome: annualized COPD exacerbation rate ratio (RR) at week 56 in patients with baseline blood eosinophil counts ≥220/mm3.
  • Funding: AstraZeneca; Kyowa Hakko Kirin.

Key results

  • GALATHEA:
    • No differences between treatment vs placebo groups in the primary outcome:
      • Benralizumab 30 mg: RR, 0.96; 95% CI, 0.80-1.15.
      • Benralizumab 100 mg: RR, 0.83; 95% CI, 0.69-1.00.
  • TERRANOVA:
    • No differences between treatment vs placebo groups in the primary outcome:
      • Benralizumab 10 mg: RR, 0.85; 95% CI, 0.71-1.01.
      • Benralizumab 30 mg: RR, 1.04; 95% CI, 0.88-1.23.
      • Benralizumab 100 mg: RR, 0.93; 95% CI, 0.78-1.10.
  • No differences in adverse events between treatment and placebo groups in both trials.

Limitations

  • Study failed to account for an effect of baseline treatment type (e.g., systemic glucocorticoids and/or antibiotics) on benralizumab response.