Subgroup Findings on Brensocatib for Non-Cystic Fibrosis Bronchiectasis, with James D. Chalmers, MBChB, PhD

As brensocatib is currently under Priority Review with the US Food and Drug Administration (FDA), it could end up becoming the first treatment for patients with non-cystic fibrosis bronchiectasis and the first approved dipeptidyl peptidase 1 (DPP1) inhibitor—a new mechanism of action that could help clinicians to manage an array of neutrophil-mediated inflammatory conditions.1

New findings from the ASPEN study suggest that brensocatib showed consistent efficacy as well as safety across 3 subgroups of patients.2 To address these data and their significance, James D. Chalmers, MBChB, PhD, professor of respiratory research at the University of Dundee, spoke with HCPLive at the American Thoracic Society (ATS) International Conference.

“ASPEN was a phase 3, double-blind, randomized placebo-controlled trial of brensocatib at 2 doses, 25 milligrams and 10 milligrams, against placebo,” Chalmers explained. “It was a global trial, and it's by far the largest trial ever conducted in patients with bronchiectasis. Patients were randomized 1:1:1 to either 25 milligrams brensocatib, 10 milligrams brensocatib, or placebo, and patients were followed up for 52 weeks. The primary outcome was the frequency of exacerbations. That's the most clinically relevant endpoint for people with bronchiectasis.”

Chalmers highlighted key secondary endpoints as well, which included time to first exacerbation, the proportion of patients that were shown to be free of exacerbations, lung function, and symptoms measured by a validated quality of life questionnaire.

In adolescents, both doses of brensocatib (10 mg and 25 mg) were shown by Chalmers and coauthors to have reduced exacerbation rates and helped preserve lung function compared to those in the placebo arm.2 The medication was also effective regardless of maintenance macrolide utilization, with lower exacerbation rates and less FEV₁ decline across the subgroups. Brensocatib also showed consistent benefits across blood eosinophil levels, with reductions observed in exacerbations, lung function preservation, and improved quality of life.

“You may know that bronchiectasis has been a neglected disease,” Chalmers said. “It's really a very recent phenomenon that people have started to try to do trials in this space, and very much a recent phenomenon that people are trying to target this particular type of pathology. So recognizing bronchiectasis as an inflammatory disease has been a key step forward, and therefore targeting this disease with anti-inflammatories, rather than repeatedly treating patients with antibiotics, is going to be a major step forward for how we treat these patients.”

“The safety data was also very reassuring, with very similar rates of adverse events between the brensocatib groups and the placebo groups,” Chalmers added.

He later touched on a variety of specific findings highlighted among the 3 subgroups, noting in particular several points related to 1 particular subgroup.

“Bronchiectasis is predominantly a neutrophil-driven inflammatory disease,” Chalmers explained. “There is also a type of inflammation called T2 inflammation, which is often associated with asthma. About 20% of patients with bronchiectasis have raised T2 biomarkers, like raised blood eosinophils. So there's a question: Will an anti-neutrophil approach work in people who have this other type of inflammation? What we've shown, which is consistent with some of our pre-clinical work, is that patients don't have neutrophilic or T2 inflammation separately; most people with bronchiectasis who have T2 inflammation also have neutrophilic inflammation.”

Consequently, Chalmers noted, the investigators demonstrated with these sub-analyses that patients respond to brensocatib the same regardless of the presence of raised blood eosinophils.

“That will be very useful clinically, because some guidelines, for example, from Australia and New Zealand, are recommending different treatment approaches for patients with high blood eosinophil counts in bronchiectasis,” Chalmers said. “And our data here suggests that for brensocatib, blood eosinophil shouldn't influence your decision to prescribe or not.”

For any additional information on this data, view the full interview segment posted above. To find out more about late-breaking data covered at ATS, view our latest conference coverage.

The quotes used in this summary were edited for the purposes of clarity.

References

1. Johnson V. Brensocatib, Potential First Treatment for Non-CF Bronchiectasis, Gets Priority Review. HCPLive. Feburary 6, 2025. Accessed May 21, 2025. https://www.hcplive.com/view/brensocatib-potential-first-treatment-non-cf-bronchiectasis-priority-review.

2. Brensocatib Shows Consistent Efficacy and Safety Across Three Prespecified Subgroups in New Data from Landmark ASPEN Study. Insmed Incorporated. May 21, 2025. https://www.prnewswire.com/news-releases/brensocatib-shows-consistent-efficacy-and-safety-across-three-prespecified-subgroups-in-new-data-from-landmark-aspen-study-302462008.html?tc=eml_cleartime.