Brensocatib Significantly Reduces Pulmonary Exacerbations in Bronchiectasis Patients

A recent phase 3 clinical trial published in the April 24, 2025, issue of the New England Journal of Medicine has demonstrated that brensocatib, a dipeptidyl peptidase-1 (DPP-1) inhibitor, effectively lowers the rate of pulmonary exacerbations in individuals with bronchiectasis. This study, led by James D. Chalmers from the University of Dundee, involved a double-blind, randomized design that included 1,680 adults and 41 adolescents with bronchiectasis. Participants were assigned to receive either 10 mg or 25 mg of brensocatib daily or a placebo in a 1:1:1 ratio for adults (and 2:2:1 for adolescents). Results showed that the annualized rate of pulmonary exacerbations was notably reduced in the brensocatib groups—1.02 and 1.04 episodes per year—compared to 1.29 in the placebo group. Furthermore, the time to first exacerbation was longer in the brensocatib groups, with hazard ratios of 0.81 and 0.83, indicating a substantial delay. After 52 weeks, nearly half of the patients on brensocatib remained free of exacerbations, versus just over 40% in the placebo group. The study also observed a modest decrease in lung function, with the forced expiratory volume in one second (FEV1) decreasing by 24 to 62 mL across all groups, and noted that adverse events were similar between groups, except for a higher incidence of hyperkeratosis in those taking brensocatib. The findings suggest that by inhibiting neutrophilic inflammation, brensocatib provides meaningful clinical benefits for patients with bronchiectasis. The research was funded by Insmed, the developer of brensocatib. Overall, this trial highlights the potential of DPP-1 inhibitors as an innovative approach to managing bronchiectasis by reducing exacerbation frequency and improving patient outcomes.