Brensocatib Improved Outcomes, Slowed Decline in People With Bronchiectasis

People with bronchiectasis receiving daily brensocatib treatment had a lower annualized rate of pulmonary exacerbations and reduced decline in forced expiratory volume in 1 second (FEV1) than those receiving placebo, according to new phase 3 trial data.1

"Bronchiectasis is a debilitating disease characterized by pulmonary exacerbations, which contribute to lung function decline and severely impact quality of life," lead investigator James Chalmers, MBChB, PhD, Professor and Consultant Respiratory Physician at the School of Medicine, University of Dundee, UK, said in a statement.2 "With limited treatment options and no approved therapies, the burden of exacerbations remains high, with many patients experiencing multiple episodes each year. For the first time, the ASPEN data published in NEJM demonstrates that a treatment which targets inflammation can reduce exacerbations and slow the rate of lung function decline. This is an exciting development and represents a potentially transformative breakthrough for people living with bronchiectasis, offering new hope for patients with this challenging condition if brensocatib is approved."

Brensocatib was evaluated in the phase 3, double-blind ASPEN trial which randomized patients with bronchiectasis (in a 1:1:1 ratio for adults and a 2:2:1 ratio for adolescents) to receive brensocatib (10 mg or 25 mg once per day) or placebo. The trial included a total of 1721 patients (1680 adults and 41 adolescents).1

Chalmers and colleagues found that the placebo group had an annualized rate of pulmonary exacerbations of 1.29, the 10-mg brensocatib group had an annualized rate of pulmonary exacerbations of 1.02 (rate ratio, 0.79 (95% CI, 0.69-0.92; adjusted P = .004), and the 25-mg brensocatib group had an annualized rate of pulmonary exacerbations of 1.04 (rate ratio, 0.81 [95% CI, 0.69-0.94; adjusted P = .005]). They found that the hazard ratio for the time to the first exacerbation was 0.81 (95% CI, 0.70-0.95; adjusted P = .02) in the 10-mg group and 0.83 (95% CI, 0.70-0.97; adjusted P = .04) in the 25-mg group.1

Altogether, 48.5% of all patients receiving brensocatib remained exacerbation-free at week 52, compared with 40.3% in the placebo group. Specifically, the 10-mg group had a rate ratio of 1.20 (95% CI, 1.06-1.37; adjusted P = .02) and the 25-mg group had a rate ratio of 1.18 (95% CI, 1.04 to 1.34; adjusted P = .04).1

Looking at FEV1, Chalmers and colleagues found that at week 52, FEV1 had declined by 50 ml in the 10-mg dose, 24 ml in the 25-mg dose, and 62 ml in the placebo group. Compared to placebo, the 10-mg group had a least-squares mean (LSM) difference of 11 mL (95% CI, -14 to 37; adjusted P = .38) and the 25-mg group had an LSM difference of 38 mL (95% CI, 11-65; adjusted P = .04). In terms of safety, investigators observed a similar incidence of adverse events across groups, with the exception of a higher incidence of hyperkeratosis with brensocatib.1

“Identifying inflammatory endotypes, including neutrophil-driven, eosinophil-driven, and mixed inflammatory endotypes, in bronchiectasis — and hence potential treatable traits — may guide preventive therapies. To further define the role of brensocatib in managing bronchiectasis, comparative trials of the drug with current guideline-based long-term antibiotic therapies are needed, as are trials incorporating validated disease phenotypes and endotypes into their design to help ensure that participants have similar clinical and pathobiologic characteristics,” Scott C. Bell, MBBS, MD, from Griffith University, and Keith Grimwood, MBChB, MD, from Gold Coast University, both in Australia, wrote in a related editorial.3

REFERENCES

1. Chalmers JD, Burgel PR, Daley CL, et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. New Eng J Med. 2025; 392 (16): 1569-1581.

2. New England Journal of Medicine Publishes Positive Results from Insmed's Pivotal Phase 3 ASPEN Study of Brensocatib in Patients with Bronchiectasis. News release. Insmed. April 23, 2025. https://www.prnewswire.com/news-releases/new-england-journal-of-medicine-publishes-positive-results-from-insmeds-pivotal-phase-3-aspen-study-of-brensocatib-in-patients-with-bronchiectasis-302436049.html

3. Bell SC, Grimwood K. Brensocatib in Bronchiectasis — A New Sheriff in Town? New Eng J Med. 2025; 392 (16): 1647-1648