Brensocatib Becomes First FDA-Approved Therapy for Bronchiectasis

The FDA has approved brensocatib (Brinsupri; Insmed) for the treatment of non–cystic fibrosis bronchiectasis, making it both the first approved therapy for this patient population and the first dipeptidyl peptidase 1 (DPP1) inhibitor approved to treat a neutrophil-mediated disease.1

Brensocatib (name; Insmed) gains FDA approval as the first treatment for bronchiectasis, offering hope to patients with the chronic lung disease. | Image Credit: Pawel - stock.adobe.com

Brensocatib is a small-molecule, oral, reversible DPP1 inhibitor.2 By blocking DPP1, it reduces the activation of neutrophil serine proteases, which are key drivers of inflammation and tissue damage in chronic lung diseases, such as bronchiectasis.

"This FDA approval represents a potential paradigm shift in how we approach non-cystic fibrosis bronchiectasis," Doreen Addrizzo-Harris, M.D., FCCP, the Fiona and Stanley Druckenmiller Professor of Pulmonary, Critical Care and Sleep Medicine at NYU Grossman School of Medicine and Director of the NYU Langone Health Bronchiectasis and NTM Program, and ASPEN investigator, said in a statement. "For the first time, we have a treatment that directly targets neutrophilic inflammation and addresses a root cause of bronchiectasis exacerbations. Based on the strength of the data and the impact we've seen in patients, I believe this could become the new standard in non-cystic fibrosis bronchiectasis care." 

This newly approved therapy offers hope for the approximately 500,000 individuals in the US affected by this chronic lung disease, which is characterized by permanently dilated bronchi resulting from a cycle of infection, inflammation, and lung tissue damage. Patients often experience frequent pulmonary exacerbations, involving chronic cough, excessive sputum production, shortness of breath, and repeated respiratory infections.

ASPEN Trial Shows Brensocatib Reduces Exacerbations, Preserves Lung Function

Today’s approval was supported by data from the ASPEN trial (NCT04594369), the largest bronchiectasis clinical trial conducted to date.3 The phase 3, double-blind trial randomized adults (1:1:1) and adolescents (2:2:1) to receive once-daily brensocatib at either 10 mg or 25 mg or placebo.2

The primary end point was the annualized rate of adjudicated pulmonary exacerbations over 52 weeks. Secondary end points included time to first exacerbation, the percentage of patients remaining exacerbation-free at week 52, changes in forced expiratory volume in 1 second (FEV1), annualized rate of severe exacerbations, and changes in quality of life.

The study enrolled 1721 patients, which included 1680 adults and 41 adolescents. Of these, 583 received 10 mg of brensocatib, 575 received 25 mg, and 563 received a placebo. The annualized exacerbation pulmonary rates were 1.02 with 10 mg, 1.04 with 25 mg, and 1.29 with placebo. Compared with placebo, the rate ratio (RR) was 0.79 (95% CI, 0.68-0.92; adjusted P = .004) for 10 mg and 0.81 (95% CI, 0.69-0.94; adjusted P = .005) for 25 mg.

Brensocatib also significantly reduced the risk of first exacerbation compared with placebo, with HRs of 0.81 (95% CI, 0.70-0.95; adjusted P = .02) for 10 mg and 0.83 (95% CI, 0.70-0.97; adjusted P = .04) for 25 mg. At week 52, 48.5% of patients in both brensocatib groups remained exacerbation-free, compared with 40.3% in the placebo group. The RR for remaining exacerbation-free was 1.20 (95% CI, 1.06-1.37; adjusted P = .02) for 10 mg and 1.18 (95% CI, 1.04-1.34; adjusted P = .04) for 25 mg.

Additionally, at week 52, FEV1 had declined by 50 mL in the 10-mg group, 24 mL in the 25-mg group, and 62 mL in the placebo group. Compared with placebo, the least-squares mean difference in FEV1 was 11mL (95% CI, -14 to 37; adjusted P = .38) with 10 mg and 38 mL (95% CI, 11-65; adjusted P = .04) with 25 mg.

“Our trial showed that treatment with brensocatib led to a lower annualized rate of exacerbations than placebo in patients with bronchiectasis, and the decline in lung function was less with the 25-mg dose of brensocatib than with placebo,” the authors concluded.

ASPEN Subgroup Analyses Confirm Efficacy Across Key Populations

Subgroup analyses presented at the American Thoracic Society International Conference in San Francisco this past May more closely examined outcomes in adolescents, as well as effects based on maintenance macrolide use and blood eosinophil count.4

In adolescents, annualized exacerbation rates were 0.35 and 0.64 with 10 mg and 25 mg of brensocatib, respectively, vs 0.87 with placebo.5 Also, 59% of patients in both dose groups remained exacerbation-free vs 35% on placebo. Lung function, as measured by FEV1, improved with both brensocatib doses, while it declined with placebo.

The second subgroup analysis found that brensocatib was effective regardless of maintenance macrolide use. Compared with placebo, patients treated with either dose experienced fewer exacerbations and a greater likelihood of remaining exacerbation-free.

Lastly, in patients with both high (≥ 300/mm3) and low (< 300/mm3) baseline blood eosinophil counts, both brensocatib doses reduced exacerbation rates, prolonged time to first exacerbation, and increased the likelihood of remaining exacerbation-free. The 25 mg dose, in particular, reduced lung function decline and showed numerical improvement in the Quality of Life-Bronchiectasis Respiratory Symptoms Domain score (QOL-B RSS) at week 52 vs placebo.

“It is critical that we understand not only how brensocatib performed across the full ASPEN population, but also how it works within individual subgroups,” James D. Chalmers, MBChB, PhD, lead investigator of the ASPEN trial, said in a press release.5 “These new analyses offer evidence of consistent efficacy and safety in key patient types…reinforcing the potential of brensocatib as a foundational treatment for this complex and heterogeneous disease.”

References

1. FDA approves Brinsupri (brensocatib) as the first and only treatment for non-cystic fibrosis bronchiectasis, a serious, chronic lung disease. News release. Insmed. August 12, 2025. Accessed August 12, 2025. https://investor.insmed.com/2025-08-12-FDA-Approves-BRINSUPRI-TM-brensocatib-as-the-First-and-Only-Treatment-for-Non-Cystic-Fibrosis-Bronchiectasis,-a-Serious,-Chronic-Lung-Disease
2. Chalmers JD, Burgel PR, Daley CL, et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2025;392(16):1569-1581. doi:10.1056/NEJMoa2411664
3. A study to assess the efficacy, safety, and tolerability of brensocatib in participants with non-cystic fibrosis bronchiectasis (ASPEN). ClinicalTrials.gov. Updated November 12, 2024. Accessed August 12, 2025. https://clinicaltrials.gov/study/NCT04594369
4. Bonavitacola J, Steinzor P, Chalmers J. ASPEN trial shows efficacy of brensocatib in different dosages. AJMC. May 31, 2025. Accessed August 12, 2025. https://www.ajmc.com/view/aspen-trial-shows-efficacy-of-brensocatib-in-different-dosages-james-chalmers-md
5. Brensocatib show consistent efficacy and safety across three prespecified subgroups in new data from landmark ASPEN study. News release. Insmed. May 21, 2025. Accessed August 12, 2025. https://investor.insmed.com/2025-05-21-Brensocatib-Shows-Consistent-Efficacy-and-Safety-Across-Three-Prespecified-Subgroups-in-New-Data-from-Landmark-ASPEN-Study