Brensocatib in non-cystic fibrosis bronchiectasis: neutrophil serine protease modulation, clinical evidence, and therapeutic positioning.

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic airway disease characterized by recurrent infection, mucus retention, neutrophilic inflammation, and pulmonary exacerbations. Brensocatib is an oral, selective, reversible dipeptidyl peptidase 1 (DPP1) inhibitor that reduces neutrophil serine protease activation and has received regulatory approval for non-cystic fibrosis bronchiectasis in patients aged 12 years and older. AREAS COVERED: This review evaluates the mechanism, clinical pharmacology, efficacy, safety, regulatory status, and therapeutic positioning of brensocatib. Literature published through 30 June 2026 was identified through PubMed, Scopus, and SciFinder-n, supplemented by prescribing information, regulatory documents, bronchiectasis guidelines, and evidence from the phase 2 WILLOW and phase 3 ASPEN trials. EXPERT OPINION: Brensocatib is a mechanism-directed preventive therapy for NCFB; the evidence base is strongest in patients with recent pulmonary exacerbations, while exact sequencing relative to macrolides and inhaled antibiotics remains uncertain. It should be integrated with airway-clearance and infection-directed management rather than viewed as a stand-alone intervention. Its long-term value will depend on appropriate patient selection, dermatologic and periodontal monitoring, affordability, comparative effectiveness, and real-world evidence on exacerbations, antibiotic use, lung-function trajectories, and patient-centered outcomes.