Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis
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
Abstract
BACKGROUND: In 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. METHODS: ); the annualized rate of severe exacerbations; and change in quality of life. RESULTS: had declined by 50 ml with the 10-mg dose, 24 ml with the 25-mg dose, and 62 ml with placebo (least-squares mean difference vs. placebo, 11 ml [95% CI, -14 to 37; adjusted P = 0.38] with the 10-mg dose and 38 ml [95% CI, 11 to 65; adjusted P = 0.04] with the 25-mg dose). The incidence of adverse events was similar across groups, except for a higher incidence of hyperkeratosis with brensocatib. CONCLUSIONS: was less with the 25-mg dose of brensocatib than with placebo. (Funded by Insmed; ASPEN ClinicalTrials.gov number, NCT04594369; EudraCT number, 2020-003688-25.).