Brensocatib—Another Therapeutic “Window of Opportunity” for Patients with Bronchiectasis

<b>Introduction:</b> Bronchiectasis is a chronic, heterogeneous airway disease characterised by irreversible bronchial dilatation, recurrent infections, and persistent inflammation, leading to progressive lung damage, frequent exacerbations, and impaired quality of life. Neutrophil-driven inflammation, largely mediated by excessive activity of neutrophil serine proteases such as neutrophil elastase, represents a central pathogenic mechanism and an important therapeutic target. <b>Methods</b>: Brensocatib, a first-in-class, selective, and reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), prevents the activation of neutrophil serine proteases during neutrophil maturation in the bone marrow. By reducing downstream protease activity, brensocatib modulates aberrant neutrophilic inflammation without broadly suppressing immune function. <b>Results:</b> Clinical studies, including the Phase-2 WILLOW trial and the Phase-3 ASPEN trial, have demonstrated that brensocatib significantly reduces exacerbation frequency, prolongs time to first exacerbation, and lowers sputum neutrophil protease activity, with a favourable safety profile. Importantly, these benefits were observed across multiple patient subgroups and in addition to standard-of-care therapies. <b>Conclusions:</b> As the first FDA-approved (12 August 2025) mechanism-based therapy for non-cystic fibrosis bronchiectasis, brensocatib represents a paradigm shift toward targeted, precision treatment of neutrophil-mediated airway disease. Its clinical efficacy, biomarker-driven rationale, and potential to reduce antibiotic dependence highlight brensocatib as a cornerstone therapy in bronchiectasis management and a promising strategy for other neutrophil-driven inflammatory conditions.