Brensocatib Shows Positive Results for Managing Bronchiectasis Symptoms

In a phase 3, double-blind trial, researchers tested whether the dipeptidyl peptidase 1 (DPP-1) inhibitor brensocatib targets the key mediator of neutrophilic inflammation caused by bronchiectasis.

Results were published in The New England Journal of Medicine.

The researchers randomly assigned patients (1,721 total; 1,680 adults in a 1:1:1 ratio and 42 adolescents in a 2:2:1 ratio) to receive brensocatib 10 mg or 25 mg once per day or placebo.

The study’s primary endpoint was the annualized rate of adjudicated pulmonary exacerbations over 52 weeks.

Secondary endpoints included time to the first exacerbation during the 52-week period, the percentage of patients who remained exacerbation-free at 52 weeks, the change in forced expiratory volume in 1 second (FEV₁), the annualized rate of severe exacerbations, and change in quality of life.

The annual 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. The researchers calculated that there was a 21% reduction in exacerbation rate with 10 mg (rate ratio [RR], 0.79; 95% CI, 0.68-0.92; P=0.004) and a 19% reduction with 25 mg (RR, 0.81; 95% CI, 0.69-0.94; P=0.005) compared to placebo.

The hazard ratio for time to first exacerbation was 0.81 for the 10-mg group (P=0.02) and 0.83 for the 25-mg group (P=0.04), indicating a delayed onset of exacerbations with treatment.

By week 52, 48.5% of patients in both brensocatib dose groups remained free of exacerbations, compared to 40.3% in the placebo group (10 mg: RR, 1.20; 95% CI, 1.06-1.37; adjusted P=0.02 and 25 mg: RR, 1.18; 95% CI, 1.04-1.34; adjusted P=0.04).

By week 52, FEV₁ had decreased by 50 mL in the 10-mg group, 24 ml in the 25-mg group, and 62 ml in the placebo group. Compared to placebo, the difference in FEV₁ decline was 11 ml with 10 mg (95% CI, -14 to 37; P=0.38) and 38 ml with 25 mg (95% CI, 11-65; P=0.04), indicating a statistically significant benefit only with the 25-mg dose.

The overall incidence of adverse events was similar between groups, though hyperkeratosis was more common among patients receiving brensocatib.

“Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV₁ was less with the 25-mg dose of brensocatib than with placebo,” the researchers concluded.

Reference

Chalmers JD, et al. N Engl J Med. 2025;392(16):1569-1581. doi:10.1056/NEJMoa2411664