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

Abstract

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.