Brensocatib Significantly Reduces Exacerbations in Bronchiectasis, confirms study

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.