Once-daily brensocatib reduced pulmonary exacerbations by 21% compared with placebo and slowed lung function decline over 52 weeks in patients with bronchiectasis, according to a recent study.
Researchers conducted a phase III, double-blind, randomized controlled trial that evaluated the efficacy and safety of brensocatib, a dipeptidyl peptidase 1 inhibitor, in patients with bronchiectasis. In the study, published in The New England Journal of Medicine, 1,721 patients were randomly assigned to receive either 10 mg or 25 mg of brensocatib or placebo once daily for 52 weeks. The primary end point was the annualized rate of adjudicated pulmonary exacerbations. Secondary end points included time to first exacerbation, proportion of patients who remained exacerbation-free, change in forced expiratory volume in one second (FEV₁), and annualized rate of severe exacerbations.
James D. Chalmers, of the Division of Respiratory Medicine and Gastroenterology at the University of Dundee in the United Kingdom, and colleagues reported that the annualized rate of pulmonary exacerbations was 1.02 events per year in the 10-mg brensocatib group and 1.04 events per year in the 25-mg group, compared with 1.29 events per year in the placebo group. The rate ratios for brensocatib vs placebo were 0.79 for the 10-mg dose and 0.81 for the 25-mg dose. The hazard ratios for the time to first exacerbation were 0.81 for the 10-mg group and 0.83 for the 25-mg group. At week 52, 48.5% of patients in both brensocatib groups remained exacerbation-free, compared with 40.3% in the placebo group.
Decline in lung function was also assessed. Only the 25-mg dose of brensocatib was associated with a statistically significant reduction in the decline of lung function compared with placebo, while the 10-mg dose did not show a significant difference. Mean FEV₁ decline was 50 ml with 10 mg, 24 ml with 25 mg, and 62 ml with placebo at week 52. The least-squares mean difference in FEV₁ decline vs placebo was 11 ml for 10 mg and 38 ml for 25 mg. Adverse event rates were similar across groups, although hyperkeratosis occurred more frequently in patients who received brensocatib. The findings suggest that once-daily brensocatib reduced exacerbation rates and slowed lung function decline in patients with bronchiectasis.
Full disclosures can be found in the published study.
