Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial

Abstract

Introduction 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 II 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. Methods 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 previous year), blood eosinophil count (<300 cells per µL or ≥300 cells per µL), 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. Results 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 per 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); P. aeruginosa culture: negative, 0.54 (0.32–0.92); positive, 0.68 (0.37–1.27)). Safety results were similar across subgroups. Discussion 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.