Brensocatib, newly approved by the FDA for noncystic fibrosis bronchiectasis (NCFB), was also associated with improvements in lung structure, on the basis of data from a substudy of 100 individuals from the trial that supported the approval. The findings were presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting.

The drug was approved by the FDA in August 2025 in 10-mg and 25-mg oral doses for adults and children aged 12 years or older, according to a press release from manufacturer Insmed. Brensocatib, an inhibitor of DPP-1, is designed to target the distinctive chronic airway inflammation associated with NCFB.

Brensocatib has been shown to reduce the risk for pulmonary exacerbations, and the researchers explored whether it could also affect disease progression as measured by changes on the CT scan, said lead author James D. Chalmers, MD, of the University of Dundee, Dundee, Scotland, in an interview. “Patients and clinicians worry about disease progression, and a treatment that could prevent disease progression would be important,” said Chalmers, who presented the findings at the meeting.

In the ASPEN phase 3 trial, once-daily brensocatib significantly reduced pulmonary exacerbations, extended the time to the first exacerbation, and increased patients’ odds of staying exacerbation-free over a 1-year follow-up compared with placebo.

In the new study, the researchers examined the effect of brensocatib on structural lung disease. They reviewed CT scans from 100 adults from the ASPEN trial including 37 who received 10 mg of brensocatib, 24 who received 25 mg of brensocatib, and 39 who received a placebo. CT scans were analyzed at baseline and after 52 weeks using the Bronchiectasis Scoring Technique for CT (BEST-CT) and the LungQ-BA.

Specifically, a 25-mg dose of brensocatib was associated with significant reductions in BEST-CT subscores of bronchiectasis with mucus plugging and mucus plugging overall (P = .0084 and P = .0154, respectively), as well as increased healthy tissue (parenchyma) compared with placebo at 52 weeks.

On the LungQ-BA, patients who received 25 mg of brensocatib showed significantly fewer bronchus artery pairs (a measure of improved bronchial wall thickness) than those who received placebo at 52 weeks (P = .0499). Additionally, the bronchus outer diameter measures were significantly smaller for patients who received 10 mg of brensocatib than for those who received placebo.

Despite the moderate sample size, the researchers saw significant reductions in mucus in patients receiving brensocatib, particularly the 25-mg dose, and an overall increase in healthy parenchyma, Chalmers told Medscape Medical News. “This suggests that brensocatib has an effect on mucus that is downstream of its anti-inflammatory activity and could have important implications for future treatment,” he added.

“My personal opinion is that along with the lung function benefit seen with the 25-mg dose of brensocatib, the data support using the 25-mg first line, although both 25-mg and 10-mg doses were approved by the FDA,” said Chalmers. The new data also show that patients with considerable mucus plugging or those at a high risk for disease progression may benefit from brensocatib, which is important as the clinical community considers which patients to prioritize for treatment, he said.

The major study limitation was the small sample size of 100 in relation to the overall trial size of more than 1700 patients, Chalmers said. In addition, the methods used to assess CT changes vary, although the BEST-CT was validated in the European Bronchiectasis Registry (EMBARC) and appeared robust, he noted.

Benefits Beyond Symptom Management

The new study of imaging signals adds weight to brensocatib’s value as an evidence-based option for patients with NCFB who have frequent exacerbations or progressive lung function decline, said Daniel A. Salerno, MD, professor of clinical thoracic medicine & surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The data complement the clinical outcomes from the ASPEN program, said Salerno, who was not involved in the study.

“The parent ASPEN trial showed fewer exacerbations, slower lung function decline, and symptom improvements; the CT substudy reports reductions in mucus plugging and some measures of bronchial wall/airway disease over 52 weeks, suggesting brensocatib’s anti-inflammatory effects may translate into actual, if modest, structural change on imaging,” said Salerno.

“Those imaging signals strengthen the argument that brensocatib can be disease-modifying for noncystic fibrosis bronchiectasis, an important point now that brensocatib (Brinsupri) has regulatory approval,” he noted.

In bronchiectasis, structural changes on CT are usually hard to demonstrate over a single year because structural disease is often considered slowly progressive, Salerno told Medscape Medical News. The nominally significant reductions in percent mucus plugging and the small improvements in percent healthy parenchyma, as well as in artificial intelligence-derived airway measures, represent a meaningful signal that supports a possible effect on disease biology beyond symptom control, he said. “However, the effects were modest and exploratory, with nominal P values, so they should be viewed as hypothesis generating rather than definitive,” he added.

In practice, “expect the largest and clearest benefits in patients with neutrophilic inflammation and prior exacerbations (the main ASPEN population), and consider brensocatib for adults and adolescents (as per the drug label) with frequent exacerbations despite guideline airway clearance and antibiotic strategies,” said Salerno. However, issues of cost, access, and payer coverage will influence real-world uptake, he noted.

Scaling Up for Real-World Data

Key limitations include the small sample size and the use of multiple comparisons that yielded nominal P values, Salerno said. Also, the BEST-CT scoring system is visual and semi-quantitative and therefore subject to reader variability, although this was mitigated somewhat by the inclusion of the LungQ-BA, he added.

Next steps for research include larger, prospectively planned imaging cohorts or all-trial imaging, with prespecified endpoints and multiplicity control to confirm and quantify structural benefits, Salerno told Medscape Medical News. Other areas for research include longer follow-up periods and phenotype analysis to identify which patients benefit most, he said. Real-world safety and effectiveness data, including cost-effectiveness and adherence, also will be needed after the drug’s rollout, he said.

The study was supported by brensocatib manufacturer Insmed, and Chalmers disclosed receiving consulting and grant income from Insmed.

Salerno disclosed having no financial conflicts of interest.