Brensocatib Significantly Reduces Exacerbations in Bronchiectasis, confirms study
Researchers have discovered in a new study that treating airway inflammation with the experimental drug brensocatib lowers the rate of pulmonary exacerbations in patients with bronchiectasis. The phase III ASPEN trial showed that the DPP-1 (dipeptidyl peptidase 1) inhibitor brensocatib reduced the annualized rate of exacerbations by about 20% versus placebo. This result indicates that brensocatib may be a viable option for patients intolerant of long-term antibiotics or exposed to antimicrobial resistance. Insmed's drug has the potential to be the first FDA-approved medicine specifically for bronchiectasis as well as the first approved DPP-1 inhibitor for clinical use. This study was published in The New England Journal of Medicine by Chalmers and colleagues.
The ASPEN trial was a global, double-blind, randomized, controlled trial with 1,721 patients with bronchiectasis across 391 sites in 35 countries. Carried out from November 2020 to March 2023, the study enrolled 1,680 adults and 41 adolescents. Adults were randomly assigned in a 1:1:1 ratio to receive once-daily oral brensocatib at doses of 10 mg or 25 mg or placebo for 52 weeks.
Participants were stratified by geographic region, sputum presence of Pseudomonas aeruginosa, and number of exacerbations during the year before screening. The trial population was roughly two-thirds female, close to 75% white, and roughly one-third P. aeruginosa-positive sputum. Approximately 30% had three or more exacerbations in the prior year, 15.2% a history of COPD, and 18.7% a history of asthma.
Key findings
• Brensocatib lowered the annualized rate of pulmonary exacerbations to 1.02 for the 10 mg group and 1.04 for the 25 mg group, as compared with 1.29 in the placebo group. This translates to rate ratios of 0.79 and 0.81 for the 10 mg and 25 mg doses, respectively (adjusted P=0.004 and P=0.005).
• Furthermore, time to first exacerbation was prolonged in the treatment groups (HR 0.81 for 10 mg, P=0.02; HR 0.83 for 25 mg, P=0.04). At 52 weeks, 48.5% of the patients on brensocatib were free from exacerbations as compared to 40.3% receiving placebo, which was a reduction by a nearly 20% relative advantage.
• The decrease in lung function according to forced expiratory volume in 1 second (FEV1) was also smaller in the patients treated with brensocatib. There was a fall of 62 mL in the placebo group by week 52, while decreases were less pronounced in the 10 mg and 25 mg brensocatib arms at 50 mL and 24 mL (P=0.04 compared 25 mg with placebo).
• The frequency of total and severe adverse events was comparable between treatment and placebo groups. Hyperkeratosis, however, was more common in the brensocatib groups: 3.0% in the 25 mg group, 1.4% in the 10 mg group, and 0.7% in the placebo group.
Brensocatib decreased pulmonary exacerbations and mitigated lung function decline in patients with bronchiectasis and had an adequate safety profile. These results strengthen its utility as a first-in-class drug focusing on neutrophilic inflammation in bronchiectasis, particularly for subjects who cannot take long-term antibiotics.
Reference:
Chalmers JD, et al "Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis" N Engl J Med 2025; DOI: 10.1056/NEJMoa2411664.
