Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis

作者：James D. Chalmers, Pierre‐Régis Burgel, Charles L. Daley, Anthony De Soyza, Charles Haworth, David Mauger, Michael R. Loebinger, Pamela J. McShane, Felix C. Ringshausen, Francesco Blasi, Michal Shteinberg, Kevin C. Mange, Ariel Teper, Carlos Fernández, Migdalia Zambrano, Chunpeng Fan, Xiangmin Zhang, Mark L. Metersky · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2411664 · 被引用次数：163 · 研究领域：Cystic Fibrosis Research Advances、Peptidase Inhibition and Analysis、Chronic Obstructive Pulmonary Disease (COPD) Research

BackgroundIn bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation. MethodsIn a phase 3, double-blind trial, we randomly assigned patients with bronchiectasis (in a 1:1:1 ratio for adults and a 2:2:1 ratio for adolescents) to receive brensocatib (10 mg or 25 mg once per day) or placebo. The primary end point was the annualized rate of adjudicated pulmonary exacerbations over a 52-week period. The secondary end points, listed in hierarchical testing order, were the time to the first exacerbation during the 52-week period; the percentage of patients remaining exacerbation-free at week 52; the change in forced expiratory volume in 1 second (FEV1); the annualized rate of severe exacerbations; and change in quality of life. Research Summary Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis ResultsA total of 1721 patients (1680 adults and 41 adolescents) underwent randomization and received brensocatib or placebo. The annualized rate of pulmonary exacerbations was 1.02 in the 10-mg brensocatib group, 1.04 in the 25-mg brensocatib group, and 1.29 in the placebo group (rate ratio, brensocatib vs. placebo, 0.79 [95% confidence interval {CI}, 0.68 to 0.92; adjusted P=0.004] with the 10-mg dose and 0.81 [95% CI, 0.69 to 0.94; adjusted P=0.005] with ...