Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis

This international phase 3, double-blind, randomized placebo-controlled trial (ASPEN) evaluated the efficacy and safety of brensocatib, an oral dipeptidyl peptidase 1 (DPP-1) inhibitor, in 1721 patients with non-cystic fibrosis bronchiectasis. Brensocatib targets neutrophil serine protease activation, a key driver of disease progression. Participants received either 10 mg or 25 mg brensocatib or placebo once daily for 52 weeks. Both brensocatib groups had significantly lower annualized rates of adjudicated pulmonary exacerbations (rate ratios: 0.79 and 0.81 for 10 mg and 25 mg, respectively) and longer time to first exacerbation compared to placebo. Approximately 48.5% of patients on brensocatib remained exacerbation-free versus 40.3% on placebo. The 25 mg dose showed a slower decline in FEV₁, suggesting possible preservation of lung function. Adverse events were generally comparable between groups, though hyperkeratosis was more common with brensocatib. The findings support brensocatib as a potential anti-inflammatory therapy to reduce exacerbation burden and disease progression in bronchiectasis.

This international phase 3, double-blind, randomized placebo-controlled trial (ASPEN) evaluated the efficacy and safety of brensocatib, an oral dipeptidyl peptidase 1 (DPP-1) inhibitor, in 1721 patients with non-cystic fibrosis bronchiectasis. Brensocatib targets neutrophil serine protease activation, a key driver of disease progression. Participants received either 10 mg or 25 mg brensocatib or placebo once daily for 52 weeks. Both brensocatib groups had significantly lower annualized rates of adjudicated pulmonary exacerbations (rate ratios: 0.79 and 0.81 for 10 mg and 25 mg, respectively) and longer time to first exacerbation compared to placebo. Approximately 48.5% of patients on brensocatib remained exacerbation-free versus 40.3% on placebo. The 25 mg dose showed a slower decline in FEV₁, suggesting possible preservation of lung function. Adverse events were generally comparable between groups, though hyperkeratosis was more common with brensocatib. The findings support brensocatib as a potential anti-inflammatory therapy to reduce exacerbation burden and disease progression in bronchiectasis.