B45-32 Effect of Brensocatib on Patient-Reported Symptoms in Patients With Non-Cystic Fibrosis Bronchiectasis: A Post Hoc Analysis of QOL-B RSS Individual Items From the ASPEN Phase 3 Trial

Rationale Brensocatib is an oral, competitive, and reversible dipeptidyl peptidase-1 inhibitor that targets neutrophilic inflammation and is approved in the US for the treatment of non-cystic fibrosis bronchiectasis (hereafter, bronchiectasis) in patients 12 years of age and older. In the randomized ASPEN trial (NCT04594369), brensocatib 10 mg and 25 mg significantly reduced exacerbation burden over 52 weeks vs placebo in patients with bronchiectasis; brensocatib 25 mg also significantly reduced lung function decline and showed nominally significant improvement in patient-reported symptoms, measured by the Quality of Life-Bronchiectasis Respiratory Symptoms Score (QOL-B RSS). In this post hoc analysis of ASPEN, we report results from the analysis of QOL-B RSS by item level and by on-study pulmonary exacerbations (PEx). Methods Adult patients with ≥2 PEx in the 12 months before screening were randomized 1:1:1 to once-daily 10-mg or 25-mg brensocatib or placebo for 52 weeks. QOL-B was completed by patients at baseline and every 2 weeks through end of trial. Nine items from the respiratory symptom domain of QOL-B were scored, assessing key respiratory symptoms of bronchiectasis (congestion, cough, sputum production, sputum color, dyspnea during activity, wheezing, chest pain, dyspnea while talking, and nocturnal cough). Analyses by on-study PEx status (0, any PEx, or any severe PEx) were also conducted. Results Across QOL-B RSS items, improvements in symptoms from baseline were observed during the 52-week treatment period, particularly with brensocatib 25 mg (Table). At week 52, the greatest differences for brensocatib 25 mg vs placebo were observed for cough, congestion, dyspnea, and sputum color (Table). Patients with on-study PEx exhibited a greater symptom burden (lower QOL-B RSS) overall vs patients without PEx. Improvements in symptoms were observed with brensocatib vs placebo regardless of the number and severity of on-study PEx (Table). Conclusions Brensocatib, particularly at the 25-mg dose, improved respiratory symptoms vs placebo across all QOL-B RSS items, including cough, congestion, dyspnea, and sputum color, the latter a validated marker associated with neutrophilic inflammation. The effect of brensocatib on symptoms was observed regardless of on-study PEx. Results were consistent with overall ASPEN results, supporting clinical benefit of brensocatib on exacerbation and lung function. Real-world data on symptom improvements in patients with bronchiectasis are warranted to confirm benefit in a broader population. This abstract is funded by: Insmed Incorporated