Late-breaking abstract: A phase 2a study of benralizumab in adults with COPD

RATIONALE: Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor alpha monoclonal antibody shown to deplete blood and airway eosinophils in subjects with asthma. We investigated the effects of benralizumab in adults with chronic obstructive pulmonary disease (COPD) and elevated airway eosinophils. METHODS: Subjects with moderate-to-severe COPD, >3% sputum eosinophils, and >1 acute exacerbation (AECOPD) in the previous year were randomized in a double-blind, placebo (PBO)-controlled, multicenter study. Subjects received PBO or 100 mg benralizumab subcutaneously on weeks 1, 4, 8, 16, 24, 32, 40, and 48. Endpoints included moderate-to-severe AECOPD rate at week 56 (primary), forced expiratory volume in 1 second (FEV 1 ), COPD-specific Saint George9s Respiratory Questionnaire (SGRQ-C), and adverse events. Efficacy analyses were conducted on the per-protocol population. RESULTS: 101 subjects were randomized to PBO (n=50) or benralizumab (n=51). Benralizumab depleted both peripheral blood and sputum eosinophils. The primary endpoint of AECOPD rate reduction vs. PBO at week 56 was not met, however pre-bronchodilator FEV 1 change from baseline was -0.059L with PBO (n=42), and 0.128L with benralizumab (n=37, P=.01). A pre-specified subgroup analysis demonstrated that in subjects with baseline eosinophils >300/uL, improvements at week 56 were greater for AECOPD rate (58% reduction, P=0.28), FEV 1 (0.318L, P=0.22), and SGRQ-C symptom domain (-13.1 points, P=0.26) for benralizumab (n=14) compared to PBO (n=7). The safety profile was similar to previous studies. CONCLUSIONS: Benralizumab did not reduce the exacerbation rate in subjects with COPD, but significantly improved lung function with an acceptable safety profile.