The ASPEN trial of brensocatib, an oral dipeptidyl peptidase 1 (DPP-1) inhibitor, showed a clear benefit for quality of life in bronchiectasis, a lower annual rate of exacerbations, and a slower rate of decline in forced expiratory volume in one second (FEV₁) vs placebo.¹ The drug was granted priority review status by the US Food and Drug Administration (FDA) and is widely expected to be approved later this year.

“We don’t know what the label will say,” cautioned Mark Metersky, MD, FCCP, Professor of Medicine, Chief of Pulmonary, Critical Care, and Sleep Medicine, and Director of the Center for Bronchiectasis Care at University of Connecticut Health. Dr. Metersky was the principal investigator at the University of Connecticut clinical trial site and coauthor on the ASPEN trial report, which was published in April.

“Patients included in the study had to have two or more exacerbations during the prior year,” Dr. Metersky said. “I have plenty of patients who have daily, distressing symptoms but who do not have two exacerbations a year—or at least they don’t have them every year. The big question is will it be FDA-approved for people who don’t have two exacerbations per year? And, if not, how are payers going to cover it?”

There are currently no FDA-approved medications for bronchiectasis, Dr. Metersky said. There is solid evidence for macrolide treatment, but only about 20% of patients are on chronic macrolide therapy. Many patients do not tolerate therapy or cannot use it because of underlying non-TB mycobacterial infection.

“When I was in training, bronchiectasis was thought to be entirely chronic infection,” said site investigator Pamela J. McShane, MD, Professor of Pulmonary and Critical Care at the University of Texas Health Science Center. “Now we understand that really bronchiectasis is driven by inflammation. This is the first time a drug has actually addressed that inflammation. We’re going to have a multipronged approach to treating bronchiectasis in the future and this is one of those prongs.”

The phase 3 trial compared two doses of once-daily brensocatib, 10 mg or 25 mg, with placebo in both adults and adolescents 12 years old and older. The reversable inhibitor of DPP-1 prevents activation of neutrophil serine proteases, which are key mediators of neutrophilic inflammation and highly active in bronchiectasis.

The primary end point was the annualized rate of adjudicated pulmonary exacerbations over 52 weeks. Secondary end points included time to first exacerbation, percentage of patients remaining exacerbation-free, change in FEV₁, annualized rate of severe exacerbations, and change in quality of life.

A total of 1,721 patients, 1,680 adults and 41 adolescents, were randomized globally.

The annualized rate of pulmonary exacerbations was 1.02 in the 10 mg group, 1.04 in the 25 mg group, and 1.29 in the placebo group, with a rate ratio of 0.79 for the 10 mg dose group (95% CI, 0.68-0.92; P = .004) and 0.81 for the 25 mg group (95% CI, 0.69-0.94; P = .005).

The hazard ratio for time to first exacerbation was 0.81 for the 10 mg group (95% CI, 0.70-0.95; P = .02) and 0.83 for the 25 mg group (95% CI, 0.70-0.97; P = .04). A total of 48.5% of the patients on brensocatib remained exacerbation-free at 52 weeks compared with 40.3% in the placebo group.

At week 52, FEV₁ had declined by 50 ml in the 10 mg dose cohort, 24 ml in the 25 mg dose cohort, and 62 ml in the placebo group. Patients in the brensocatib groups also showed improved quality of life compared with patients in the placebo group by both BEST symptom and bronchiectasis quality of life scores.

“The most shocking thing from the study was the impact it had on FEV₁,” said Charles L. Daley, MD, FCCP, Chief of Mycobacterial and Respiratory Infections at National Jewish Health and ASPEN site investigator. “The decline in FEV₁ slowed significantly. You can tell someone that if you go on this drug, there is a good chance your pulmonary function is going to remain better than if you don’t.

“What happens in medicine is that if you have a condition and don’t have anything that you can do to improve it, you don’t look for it,” he continued. “Now we have something for bronchiectasis and I’m hoping that clinicians, particularly pulmonologists, will get more interested in bronchiectasis.”

1. 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