A ONCE-daily oral therapy targeting neutrophilic inflammation has shown promise in reducing exacerbations in patients with bronchiectasis, according to results from a large Phase 3 trial.
The double-blind, randomised study enrolled 1,721 patients, including 1,680 adults and 41 adolescents, and allocated them to receive either 10 mg or 25 mg of brensocatib, or placebo. Patients were followed over a 52-week period, with the primary endpoint being the annualised rate of adjudicated pulmonary exacerbations. Secondary endpoints included time to first exacerbation, the proportion of patients remaining exacerbation-free at 1 year, change in FEV1, the rate of severe exacerbations, and quality of life.
Brensocatib significantly reduced the annualised rate of pulmonary exacerbations compared to placebo. Patients receiving 10 mg and 25 mg had annualised exacerbation rates of 1.02 and 1.04, respectively, versus 1.29 in the placebo group. This corresponded to rate ratios of 0.79 (95% CI, 0.68–0.92; P=0.004) and 0.81 (95% CI, 0.69–0.94; P=0.005), respectively. The time to first exacerbation was also significantly prolonged, with hazard ratios of 0.81 (P=0.02) and 0.83 (P=0.04) for the 10 mg and 25 mg doses, respectively. At Week 52, 48.5% of patients on either dose remained exacerbation-free, compared with 40.3% of those on placebo (P=0.02 for 10 mg; P=0.04 for 25 mg). Decline in FEV1 was least in the 25 mg group (-24 mL), versus −50 mL in the 10 mg group and -62 mL with placebo. Only the higher dose showed a statistically significant benefit in lung function decline versus placebo (P=0.04). Adverse events were generally balanced across groups, though hyperkeratosis was more common with brensocatib.
These findings suggest that brensocatib is an effective and well-tolerated treatment for reducing exacerbation frequency in bronchiectasis. Its impact on lung function preservation at higher doses warrants further exploration in long-term studies.
Reference
Chalmers JD et al; ASPEN Investigators. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2025;392(16):1569-81.
