Brensocatib for Non-Cystic Fibrosis Bronchiectasis: Patient Selection, ASPEN Data, and Safety Profile

　　1.Overview and Regulatory Background

　　Brensocatib(brand name:Brinsupri)is the first disease-modifying therapy for non-cystic fibrosis bronchiectasis(non-CF bronchiectasis)approved by the U.S.FDA on August 12,2025.This approval marked a breakthrough in a field that had long lacked targeted treatment options.

　　2.ASPEN Phase 3 Data and Patient Selection

　　The approval was supported by the global,randomized,double-blind,placebo-controlled ASPEN Phase 3 trial(NCT04594369),which enrolled over 1,700 patients and lasted 52 weeks.Key results include:

　　Reduced Exacerbations:Both 10 mg and 25 mg doses met the primary endpoint,reducing the annualized exacerbation rate by 20%compared to placebo.

　　Preserved Lung Function:The 25 mg dose also slowed the decline in forced expiratory volume in one second(FEV1),demonstrating potential to delay disease progression.

　　Given the heterogeneity of bronchiectasis,not all patients benefit equally.Ideal candidates include:

　　Frequent Exacerbators:Patients with recurrent acute exacerbations are the primary beneficiaries.

　　High Symptom Burden:Patients with frequent cough and large amounts of purulent sputum,even without frequent exacerbations,may benefit based on the drug’s mechanism and trial patterns.

　　Rapid Lung Function Decliners:The 25 mg dose is a potential option for patients with rapidly declining FEV1,as it has shown an impact on slowing this decline,though specific subgroup data are still pending.

　　3.Safety Profile and Tolerability Management

　　The most common adverse events in the ASPEN trial were consistent with earlier safety data.Key tolerability notes:

　　Periodontal Safety:The Phase 3 trial did not show a significant signal of increased periodontal disease risk.Although the drug label mentions unique tolerability issues like hyperkeratosis and periodontal changes,these did not prevent patients from starting or continuing therapy in clinical practice.

　　Skin Reactions:Some clinicians observed skin thickening and peeling,most commonly on the knees,elbows,tops of feet,and backs of hands,but this was not a common finding.

　　Clinical Advice:Patients are advised to brush twice daily,floss,and have regular dental check-ups to detect and manage any periodontal changes early.

　　4.Guideline Update and Clinical Outlook

　　In 2026,the American College of Chest Physicians(ACCP)released the first North American clinical practice guideline for adult bronchiectasis,including long-term brensocatib as one of 13 conditional recommendations for patients with frequent exacerbations.This solidifies its role in standard care.

　　However,unmet needs such as chronic cough,sputum burden,and disease progression persist,requiring comprehensive management strategies.