Efficacy of Brensocatib in Patients with Non-Cystic Fibrosis Bronchiectasis With vs Without Maintenance Use of Macrolides: An Analysis of the ASPEN Trial

Purpose Neutrophilic inflammation is key to the pathophysiology of bronchiectasis and neutrophil serine proteases (NSPs) are associated with disease progression and worse clinical outcomes. Brensocatib, an oral, competitive, and reversible inhibitor of DPP1, prevents activation of NSPs. In the ASPEN trial (NCT04594369), brensocatib 10mg and 25mg significantly reduced the annualized rate of adjudicated pulmonary exacerbations (PEx) over 52 weeks vs placebo; the 25mg dose also significantly reduced lung function decline and nominally significantly improved patient-reported symptoms. Here, we report ASPEN subgroup analysis findings in patients with or without maintenance macrolide use. Methods Patients (12-85 y) with bronchiectasis and a history of PEx in the previous 12 months were randomized to once-daily brensocatib (10mg or 25mg) or placebo for 52 weeks. Subgroup analyses were explored in patients with or without maintenance macrolide use (≥3 months) at baseline. Endpoints included PEx rate, time to first PEx, patients remaining PEx-free, FEV 1 change, and safety. Results Baseline characteristics were balanced, with some differences indicating greater disease severity among patients with maintenance macrolide use. In both subgroups vs placebo, brensocatib 10mg and 25mg reduced the PEx rate (RR [95% CI] without macrolide: 10mg=0.78 [0.66-0.93], 25mg=0.80 [0.67-0.95]; with macrolide: 10mg=0.79 [0.58-1.06], 25mg=0.79 [0.58-1.08]), prolonged the time to first PEx (HR [95% CI)] without macrolide: 10mg=0.79 [0.66-0.94], 25mg=0.82 [0.68-0.98)]; with macrolide: 10mg=0.93 [0.66-1.33], 25mg=0.85 [0.59-1.21]), and increased the odds of remaining PEx-free (OR [95% CI] without macrolide: 10mg=1.44 [1.10-1.89], 25mg=1.40 [1.07-1.84]; with macrolide: 10mg=1.41 [0.78-2.57], 25mg=1.59 [0.88-2.90]). Brensocatib 25mg reduced FEV 1 decline at week 52 vs placebo regardless of macrolide use (LS mean difference [95% CI] without macrolide: 35mL [5-66]; with macrolide: 44ml [-16 to 104]). Adverse events were similar across treatment groups, and consistent with the overall ASPEN data. Conclusions Both brensocatib doses reduced the annualized rate of PEx, and brensocatib 25mg reduced lung function decline regardless of baseline maintenance macrolide use. Encore abstract. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany