Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.

Summary

In a 52-week, double-blind phase 3 trial (n=1,721), once-daily brensocatib (10 or 25 mg) significantly reduced the annualized rate of pulmonary exacerbations versus placebo and delayed time to first exacerbation. Nearly half of brensocatib-treated patients remained exacerbation-free at week 52 compared with 40.3% on placebo.

Key Findings

• Annualized exacerbation rate reduced to 1.02–1.04 on brensocatib vs 1.29 on placebo (rate ratio 0.79 and 0.81; adjusted P=0.004 and 0.005).
• Time to first exacerbation was prolonged (HR 0.81 and 0.83; adjusted P=0.02 and 0.04).
• 48.5% of brensocatib patients remained exacerbation-free at week 52 vs 40.3% with placebo.

Clinical Implications

Brensocatib may become an option to prevent exacerbations in bronchiectasis, particularly for patients with neutrophil-dominant inflammation; integration into guidelines will depend on long-term safety and functional outcomes.

Limitations

• Abstract truncation limits detail on lung function outcomes and safety signals.
• Adolescent subgroup small; long-term safety and effects on FEV1 and quality of life require further reporting.

Future Directions

Assess long-term safety, durability of efficacy, impact on lung function and microbiology, and identify biomarkers of response to anti–neutrophil protease therapy.