Benralizumab in bronchiectasis: results from the phase 3 MAHALE study

Background Bronchiectasis is a chronic, inflammatory lung disease with distinct endotypes, often defined by inflammatory cells in blood and sputum. We assessed safety and efficacy of benralizumab, an anti-IL-5Rα monoclonal antibody, in patients with bronchiectasis and eosinophilic inflammation. Methods MAHALE ( NCT05006573 ) was a 52-week, randomised, multicentre, double-blind, phase 3 study. Patients with bronchiectasis and no comorbid pulmonary conditions were randomised 1:1 to receive subcutaneous benralizumab 30 mg or placebo every 4 weeks. Primary endpoint was annualised exacerbation rate. Secondary endpoints included: time to first exacerbation, change from baseline in respiratory symptoms, lung function, health-related quality of life (HRQoL), respiratory health status and safety. In August 2022, the study was terminated early due to recruitment challenges related to the COVID-19 pandemic. Results One-hundred patients were randomised and 99 were dosed (benralizumab, n=54; placebo, n=45); 21 had blood eosinophil counts ≥300 cells·µL −1 . Notable imbalances in baseline characteristics between treatment arms suggested patients receiving benralizumab had more severe disease. The study did not enrol enough patients to meet power requirement to detect differences in efficacy endpoints between benralizumab and placebo. At the end of the study, annualised exacerbation rates were not significantly different between treatment groups (rate ratio [95% confidence interval]: 1.14 [0.71–1.82], p=0.59). Change in respiratory symptoms and HRQoL were similar between treatment groups. Benralizumab was well tolerated. Conclusions A small sample size, with eosinophil counts predominantly <300 cells·µL −1 and imbalances at baseline, limit interpretation of data on clinical outcomes following benralizumab treatment. Adequately powered randomised trials are needed in the population of interest.