Efficacy of Brensocatib in Patients with high or low blood eosinophil counts: An Analysis of the ASPEN Trial

Purpose Neutrophilic inflammation plays a key role in the pathophysiology of bronchiectasis. Neutrophil serine proteases (NSPs) are associated with disease progression and poorer clinical outcomes. Brensocatib, an oral, competitive, and reversible inhibitor of DPP1, prevents activation of NSPs. In the phase 3 ASPEN trial (NCT04594369), once-daily 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. Eosinophilia is present in ~20% of patients with bronchiectasis. Here, we report subgroup findings in ASPEN patients based on blood eosinophil count at screening. Methods Patients (12-85 y) with bronchiectasis had a history of PEx in the 12 months prior to screening (adults≥2, adolescents≥1) received once-daily brensocatib (10mg or 25mg) or placebo for 52 weeks. Patients were grouped based on high (≥300/μL) or low (