Brensocatib Reduces Exacerbation Risk and Slows Lung Function Decline in Patients with Bronchiectasis
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on May 16th, 2025
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Patients with bronchiectasis typically present with a chronic cough and excessive sputum production. The progressive decline in lung function associated with this disease is largely driven by neutrophil-mediated inflammation and damage to the mucociliary membrane. Current clinical guidelines generally recommend the use of mucoactive agents to alleviate symptoms and antibiotics to prevent bacterial infections. Recently, a study funded by Insmed and published in The New England Journal of Medicine examined the use of brensocatib, a drug aimed at managing bronchiectasis by inhibiting neutrophil activity.
This phase 3 clinical trial enrolled 1,721 participants with confirmed bronchiectasis based on computed tomography (CT) scans. To focus exclusively on bronchiectasis, individuals with coexisting cystic fibrosis, asthma, or chronic obstructive pulmonary disease were excluded. Assessment using the Bronchiectasis Severity Index yielded an average score of 7.1 out of a maximum of 9, indicating moderate to severe disease. Nearly all participants had experienced at least two exacerbations in the previous year, and about one-quarter had required hospitalization within the past two years.
Participants were randomly assigned to receive either a placebo or one of two brensocatib doses—10 mg or 25 mg—administered once daily for 52 weeks. Brensocatib is a small-molecule inhibitor that selectively targets dipeptidyl peptidase 1 (DPP1), an enzyme essential for activating neutrophil serine proteases during cell maturation. By inhibiting DPP1, the drug prevents the conversion of protease precursors into their active forms, thereby reducing neutrophil-driven airway inflammation and tissue damage.
After one year of treatment, brensocatib was found to reduce the risk of pulmonary exacerbations by 21%, with no significant difference in this outcome between the 10 mg and 25 mg groups. However, patients receiving the 25 mg dose exhibited significantly less pulmonary decline compared to both the 10 mg and placebo groups, as measured by post-bronchodilator forced expiratory volume in one second (FEV1). The authors suggest that the observed preservation of lung function may be due to reduced airway inflammation and protection of the airway’s structural integrity.
This phase 3 clinical trial enrolled 1,721 participants with confirmed bronchiectasis based on computed tomography (CT) scans. To focus exclusively on bronchiectasis, individuals with coexisting cystic fibrosis, asthma, or chronic obstructive pulmonary disease were excluded. Assessment using the Bronchiectasis Severity Index yielded an average score of 7.1 out of a maximum of 9, indicating moderate to severe disease. Nearly all participants had experienced at least two exacerbations in the previous year, and about one-quarter had required hospitalization within the past two years.
Participants were randomly assigned to receive either a placebo or one of two brensocatib doses—10 mg or 25 mg—administered once daily for 52 weeks. Brensocatib is a small-molecule inhibitor that selectively targets dipeptidyl peptidase 1 (DPP1), an enzyme essential for activating neutrophil serine proteases during cell maturation. By inhibiting DPP1, the drug prevents the conversion of protease precursors into their active forms, thereby reducing neutrophil-driven airway inflammation and tissue damage.
After one year of treatment, brensocatib was found to reduce the risk of pulmonary exacerbations by 21%, with no significant difference in this outcome between the 10 mg and 25 mg groups. However, patients receiving the 25 mg dose exhibited significantly less pulmonary decline compared to both the 10 mg and placebo groups, as measured by post-bronchodilator forced expiratory volume in one second (FEV1). The authors suggest that the observed preservation of lung function may be due to reduced airway inflammation and protection of the airway’s structural integrity.