Targeting neutrophilic inflammation in obstructive airway disease - A narrative review of brensocatib therapy

Abstract

Brensocatib is an oral inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil serine proteases. Its potential to reduce neutrophil-driven inflammation has generated interest across a range of chronic inflammatory and respiratory conditions, particularly non-cystic fibrosis (CF) bronchiectasis. As the body of evidence supporting brensocatib continues to expand, there is a clear need for a comprehensive, rigorous, and practical narrative review to consolidate current knowledge and highlight gaps for future research. The aim of this narrative review was to systematically examine and synthesize the existing literature on brensocatib, including its pharmacology, therapeutic applications, clinical trial outcomes, safety profile, and ongoing research efforts. A systematic search was performed across major databases, EMBASE, MEDLINE, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov, through April 2025. Studies involving brensocatib in preclinical or clinical contexts were thoroughly reviewed to evaluate its efficacy and safety. Data were extracted on study design, population, dosage, outcomes, adverse events (AEs), and key findings. The most extensively studied indication was non-CF bronchiectasis, where brensocatib demonstrated a reduction in exacerbation rates and neutrophil protease activity. Preliminary evidence also suggests potential applications in CF, chronic obstructive pulmonary disease, and other neutrophilic conditions. An evaluation of the safety data indicates that the AEs reported are generally mild to moderate in severity. Brensocatib demonstrates potential as a novel anti-inflammatory therapy targeting neutrophil-mediated disease mechanisms. Further research is needed to evaluate its long-term efficacy, safety across a broader population, and its role in combination therapies.

Keywords: Brensocatib; Bronchiectasis; Dipeptidyl peptidase 1; Inflammation; Neutrophil elastase; Neutrophils.