Brensocatib Tablets (Brinsupri)
September 30, 2025 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved brensocatib, the first dipeptidyl peptidase-1 (DPP-1) inhibitor and the first drug approved for non-cystic fibrosis bronchiectasis (NCFB). Brensocatib, a once-a-day oral agent, was given a priority review and was given a Breakthrough Therapy Designation. It is distributed by Insmed Incorporated as Brinsupri.
Indications
Brensocatib is indicated for the treatment of NCFB in adult and pediatric patients 12 years of age and older.1
Dosage
The recommended dose is 10 mg or 25 mg orally once daily with or without food.1 Brensocatib is available as 10-mg and 25-mg tablets.
Potential Advantages
Brensocatib is the first-in-class DPP-1 inhibitor and the first approved treatment for NCFB.
Potential Disadvantages
Brensocatib has been associated with an increase in dermatologic adverse reactions, including rash, dry skin, and hyperkeratosis.1 It also is associated with an increase in gingival and periodontal adverse reactions. The use of live attenuated vaccines should be avoided because the safety and effectiveness of these vaccines are unknown.1 The incidence of skin cancer was 1.9% in subjects treated with brensocatib 25 mg compared to 1.1% in placebo-treated subjects, and there was a 1.6% incidence of alopecia vs. 0.4% in the placebo group.1 Brensocatib may increase liver enzymes (e.g., aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase).1
Comments
DPP-1 activation of pro-inflammatory neutrophil serine proteases (NSPs) (e.g., neutrophil elastase, proteinase 3, cathepsin G) is implicated in the pathogenesis of neutrophil-mediated NCFB inflammation.1 Elevated levels of NSPs in the sputum are associated with more severe disease, increased risk of exacerbations, and more rapid decline in lung function.2 Brensocatib is a competitive, reversible inhibitor of DPP-1.1 The efficacy of brensocatib was evaluated in two randomized, double-blind, placebo-controlled, parallel-group clinical trials (ASPEN [Phase III] and WILLOW [Phase II]).1,3,4 The participant demographics and clinical characteristics were similar between the trials: mean ages 60-64 years, 64% to 68% female, 74% to 88% white, 29% to 33% with three or more pulmonary exacerbations in the prior 12 months, 30% to 34% former smokers, mean percentage predicted forced expiratory volume in one second (FEV1) of 68% to 74%, and 35% positive sputum for Pseudomonas aeruginosa. ASPEN (n = 1721) was a 52-week study with participants randomized to brensocatib< 10 mg (n = 583), 25 mg (n = 575), or placebo (n = 563) arms. The primary efficacy endpoint was the annualized rate of adjudicated pulmonary exacerbation (PEx) evaluated over the 52-week period. This was defined as worsening of three or more of the following major symptoms over 48 hours: increased cough, increased sputum volume or change in sputum consistency, increased sputum purulence, increased breathlessness, decreased exercise tolerance, fatigue and/or malaise, and hemoptysis, resulting in a healthcare provider’s decision to prescribe systemic antibiotics. Severe PEx was defined as requiring intravenous antibiotics and/or hospitalization. Secondary endpoints included the percentage of participants remaining exacerbation-free at week 52 and change from baseline in postbronchodilator FEV1. Brensocatib (10 mg or 25 mg) treatment vs. placebo reduced the annualized rate of PEx by about 20% (1.02 and 1.04 vs. 1.29), and the brensocatib-treated groups were about 40% more likely to be PEx free at week 52. In each drug group, the percent exacerbation-free was 48.5% vs. 40.3% for placebo. There were no differences in annualized rate of severe PEx. At week 52 the decline in FEV1 was less with the 25 mg compared to placebo. WILLOW was a 24-week trial with the primary endpoint of the time to first PEx.3
Participants were randomized to brensocatib 10 mg (n = 82), 25 mg (n = 87), or placebo (n = 87). The time to first PEx was about 40% longer for each dose. In an exploratory analysis, brensocatib reduced the activities of major NSPs in sputum and white blood cell extracts by week 4.5
Clinical Implications
Bronchiectasis is an incurable chronic inflammatory (predominately neutrophilic) disease characterized by permanent dilation of the bronchi.6 These patients have daily cough and sputum production and frequent exacerbations, lung infections, decreased lung function, and increased mortality. It is a self-perpetuating cycle of inflammation, impaired mucociliary clearance, structural airway damage, and recurrent infection promoting progression of the disease.3 Prevalence is estimated to be 500,000 people in United States.7 It increases with age, with 7 per 100,000 people aged 18-34 years vs. 812 per 100,000 people in those aged ≥ 75 years and is more common in women.7 Goals of treatment are to lessen symptom burden, improve quality of life, reduce exacerbations and prevent disease progression.6,7 Current treatments include airway clearance techniques, mucoactive agents, inhaled glucocorticoids, bronchodilators, antimuscarinics, and long-term antibiotics (e.g., macrolides) for treating infections. Brensocatib is the first DPP-1 inhibitor to target the inflammatory component by preventing activation of NSPs, resulting in a reduction of exacerbations, and may slow decline in FEV1 at the higher dose. The cost was not available at the time of this review, with an estimated availability in the third quarter of 2025.
William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.
James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco. References
References
- U.S. Food and Drug Administration. Brinsupri prescribing information. Insmed Incorporated. Revised August 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217673s000lbl.pdf
- Chalmers JD, Moffitt KL, Suarez-Cuartin G, et al. Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis. Am J Respir Crit Care Med. 2017;195(10):1384-1393.
- Chalmers JD, Burgel P-R, Daley CL, et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2025;392(16):1569-1581.
- Chalmers JD, Haworth CS, Metersky ML, et al. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2020;383(22):2127-2137.
- Cipolla D, Zhang J, Korkmaz B, et al. Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: Results from the WILLOW trial. Respir Res. 2023;24(1):133-147.
- Choi H, McShane PJ, Aliberti S, Chalmers JD, et al. Bronchiectasis management in adults: state of the art and future directions. Eur Respir J. 2024;63(6):2400518.
- Barker AF, Karamooz E. Non-cystic fibrosis bronchiectasis in adults: A review. JAMA. 2025;334(3):253-264.
The U.S. Food and Drug Administration has approved brensocatib, the first dipeptidyl peptidase-1 inhibitor and the first drug approved for non-cystic fibrosis bronchiectasis.
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