TARGETING inflammation at its root, a new therapy reduces bronchiectasis exacerbations and slows lung function decline, according to results from a Phase III clinical trial.
Bronchiectasis, a chronic lung disease characterized by airway inflammation and recurrent exacerbations, remains a challenging condition for clinicians. Neutrophilic inflammation, a key driver of disease progression, has now emerged as a therapeutic target. A phase 3 trial evaluating brensocatib, a dipeptidyl peptidase 1 (DPP-1) inhibitor, demonstrated significant reductions in exacerbation rates among patients with bronchiectasis.
In this double-blind, randomized trial, 1,721 patients (predominantly adults) were assigned to receive either brensocatib (10 mg or 25 mg daily) or placebo over a 52-week period. The primary endpoint assessed the annualized rate of adjudicated pulmonary exacerbations.
Results showed that patients receiving brensocatib experienced fewer exacerbations—1.02 per year with 10 mg and 1.04 with 25 mg—compared to 1.29 in the placebo group. These reductions corresponded to rate ratios of 0.79 (95% CI, 0.68 to 0.92; P=0.004) for the 10-mg dose and 0.81 (95% CI, 0.69 to 0.94; P=0.005) for the 25-mg dose. Time to first exacerbation was also delayed with brensocatib, with hazard ratios of 0.81 and 0.83 for the respective doses.
Nearly half of the patients receiving brensocatib (48.5%) remained exacerbation-free at one year, compared with 40.3% in the placebo group. Additionally, lung function decline, measured by forced expiratory volume in one second (FEV1), was less pronounced in the 25-mg brensocatib group, which saw a 24 ml reduction versus 62 ml with placebo (mean difference of 38 ml; P=0.04).
Adverse events were comparable across groups, though hyperkeratosis was more frequently observed in patients receiving brensocatib.
These findings suggest that targeting neutrophil serine proteases with brensocatib may offer a new approach for managing bronchiectasis, reducing exacerbation frequency and preserving lung function. As this therapeutic strategy moves forward, it could represent a shift in bronchiectasis care, where inflammation control becomes central to treatment plans.
Reference:
Chalmers JD et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2024;390:1533-1544.
