Revolutionizing Bronchiectasis Care: The Brensocatib Breakthrough

The potential introduction of brensocatib into care for non–cystic fibrosis bronchiectasis marks a notable moment in a field with substantial unmet need, but its regulatory status remains under review and should be described as investigational rather than approved.

Brensocatib offers a potential new anti-inflammatory option for bronchiectasis, opening avenues for patient management; however, it remains investigational and is not described here as benefiting from any specific expedited FDA designation.

For patients who often face frequent hospital visits, this candidate therapy reflects a shift toward more sustained respiratory health if late-stage efficacy is confirmed. Brensocatib has demonstrated a reduction in respiratory exacerbations and evaluated effects on quality of life in trials; in the phase 2 WILLOW study, the primary endpoint showed fewer exacerbations versus placebo with a statistically significant reduction in annualized exacerbation rate, while between-group differences in quality-of-life measures were modest and not consistently significant.

These data frame an inflection point in bronchiectasis management that prioritizes long-term outcomes but still requires confirmation. The WILLOW phase 2 trial reported efficacy and safety findings, and the phase 3 ASPEN program has been designed to confirm these results and inform regulatory review, rather than to substantiate an approval already granted.

Brensocatib represents a novel strategy that complements existing treatments like antibiotics, acting as a first-in-class dipeptidyl peptidase-1 inhibitor that reduces activation of neutrophil serine proteases, a key driver of airway inflammation.

In practice, if authorized, clinicians would need to consider placement alongside airway clearance techniques, macrolide prophylaxis in appropriate patients, vaccination, and prompt treatment of infectious exacerbations. Such implementation decisions will hinge on identifying phenotypes most likely to benefit and on balancing anti-inflammatory gains against safety, monitoring requirements, and cost.

The next step is to monitor long-term safety, durability of exacerbation reduction, lung function trajectory, pathogen colonization, and healthcare utilization to confirm these promising trends.

While many patients continue to experience exacerbations despite optimized care, outcomes vary by bronchiectasis phenotype and adherence to comprehensive management that includes airway clearance, vaccination, and infection control measures.

Ultimately, brensocatib should be viewed within a comprehensive, multidisciplinary framework that integrates patient education, physiotherapy, microbiology-guided therapy, and attention to comorbidities. This broader context underscores why investigational anti-inflammatory approaches are being explored and how they might fit into evolving standards once definitive evidence is available.

Key Takeaways:

• Brensocatib is investigational for non–cystic fibrosis bronchiectasis; it is not yet included in major guidelines.
• Phase 2 data suggest fewer exacerbations versus placebo, with quality-of-life differences modest and inconsistent.
• Phase 3 confirmation and long-term safety data are needed to determine clinical adoption and placement.
• Any future use should complement comprehensive care, including airway clearance, infection control, and vaccination.