| Title: |
Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis |
| Authors: |
Chalmers, James D.; Burgel, Pierre Régis; Daley, Charles L.; De Soyza, Anthony; Haworth, Charles S.; Mauger, David; Loebinger, Michael R.; McShane, Pamela J.; Ringshausen, Felix C.; Blasi, Francesco; Shteinberg, Michal; Mange, Kevin; Teper, Ariel; Fernandez, Carlos; Zambrano, Migdalia; Fan, Chunpeng; Zhang, Xiangmin; Metersky, Mark L. |
| Source: |
Chalmers, J D, Burgel, P R, Daley, C L, the ASPEN Investigators, De Soyza, A, Haworth, C S, Mauger, D, Loebinger, M R, McShane, P J, Ringshausen, F C, Blasi, F, Shteinberg, M, Mange, K, Teper, A, Fernandez, C, Zambrano, M, Fan, C, Zhang, X & Metersky, M L 2025, 'Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis', New England Journal of Medicine, vol. 392, no. 16, pp. 1569-1581. https://doi.org/10.1056/NEJMoa2411664 |
| Publication Year: |
2025 |
| Description: |
Background In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation. Methods In a phase 3, double-blind trial, we randomly assigned 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 primary end point was the annualized rate of adjudicated pulmonary exacerbations over a 52-week period. The secondary end points, listed in hierarchical testing order, were the time to the first exacerbation during the 52-week period; the percentage of patients remaining exacerbation-free at week 52; the change in forced expiratory volume in 1 second (FEV1); the annualized rate of severe exacerbations; and change in quality of life. Results A total of 1721 patients (1680 adults and 41 adolescents) underwent randomization and received brensocatib or placebo. The annualized rate of pulmonary exacerbations was 1.02 in the 10-mg brensocatib group, 1.04 in the 25-mg brensocatib group, and 1.29 in the placebo group (rate ratio, brensocatib vs. placebo, 0.79 [95% confidence interval {CI}, 0.68 to 0.92; adjusted P=0.004] with the 10-mg dose and 0.81 [95% CI, 0.69 to 0.94; adjusted P=0.005] with the 25-mg dose). The hazard ratio for the time to the first exacerbation was 0.81 (95% CI, 0.70 to 0.95; adjusted P=0.02) with the 10-mg dose and 0.83 (95% CI, 0.70 to 0.97; adjusted P=0.04) with the 25-mg dose. In each brensocatib group, 48.5% of patients remained exacerbation-free at week 52, as compared with 40.3% in the placebo group (rate ratio, 1.20 [95% CI, 1.06 to 1.37; adjusted P=0.02] with the 10-mg dose and 1.18 [95% CI, 1.04 to 1.34; adjusted P=0.04] with the 25-mg dose). At week 52, FEV1 had declined by 50 ml with the 10-mg dose, 24 ml with the 25-mg dose, and 62 ml with placebo (least-squares mean ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0028-4793; 1533-4406 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40267423; info:eu-repo/semantics/altIdentifier/pissn/0028-4793; info:eu-repo/semantics/altIdentifier/eissn/1533-4406 |
| DOI: |
10.1056/NEJMoa2411664 |
| Availability: |
https://pure.eur.nl/en/publications/c65c1af4-6223-4612-8f25-ac0e46bf3d9e; https://doi.org/10.1056/NEJMoa2411664; https://pure.eur.nl/ws/files/200351899/NEJMoa2411664.pdf; https://www.scopus.com/pages/publications/105003982178 |
| Rights: |
info:eu-repo/semantics/openAccess ; https://www.eur.nl/en/library/media/2024-12-researchoutputsundertaverne-backgroundandtermsofusev2 |
| Accession Number: |
edsbas.CFB8ACCD |
| Database: |
BASE |