Brensocatib in Patients With Bronchiectasis: Subgroup Analyses From the WILLOW Trial

Bronchiectasis is a chronic inflammatory airway disease. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces pulmonary inflammation by preventing the activation of neutrophil serine proteases. In the phase 2 WILLOW trial, brensocatib prolonged time to first exacerbation in patients with bronchiectasis. In this post-hoc analysis we compare clinical outcomes in patients from WILLOW according to baseline disease characteristics. Adults with bronchiectasis treated with brensocatib (10 or 25 mg) or placebo once-daily were analysed by baseline Bronchiectasis Severity Index (BSI) score (≤4 mild, 5–8 moderate, or ≥9 severe), exacerbation history (2 or ≥3 in the prior year), blood eosinophil count (<300 cells·µL −1 or ≥300 cells·µL −1 ), long-term macrolide use (≥6 months; no or yes), and Pseudomonas aeruginosa culture at screening (negative or positive). End points were time to first exacerbation, annualised exacerbation rate, change in lung function from baseline, and safety. All patients who received brensocatib were pooled and compared with placebo. Treatment with brensocatib versus placebo was associated with a longer time to first exacerbation (hazard ratio 95% confidence interval, BSI: ≤4, 0.28 0.08–0.96; 5–8, 0.75 0.35–1.60; ≥9, 0.61 0.35–1.04; prior exacerbations: 2, 0.56 0.34–0.90; ≥3, 0.71 0.32–1.59; blood eosinophils/µL: <300, 0.66 0.42–1.06; ≥300, 0.49 0.20–1.20; long-term macrolide use: no, 0.60 0.38–0.94; yes, 0.60 0.25–1.45; Pseudomonas aeruginosa culture: negative, 0.54 0.32–0.92; positive, 0.68 0.37–1.27). Safety results were similar across subgroups. Patients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbation versus placebo across all key baseline disease characteristics.