Brensocatib improves clinical outcomes in bronchiectasis patients: NEJM
Delhi: The use of brensocatib was shown to improve clinical outcomes in bronchiectasis patients, in a 24-week trial. The findings of the study are published in the New England Journal of Medicine. Brensocatib, an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), helped in reducing neutrophil serine protease activity.
Bronchiectasis patients experience frequent exacerbation that are thought to be linked to neutrophilic inflammation. In bronchiectasis patients, the quantity and activity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum, and are increased further during exacerbation.
James D. Chalmers, Ninewells Hospital and Medical School, Dundee (J.D.C.), and colleagues performed phase 2, randomized, double-blind, placebo-controlled trial. It included 256 patients with bronchiectasis who had had at least two exacerbations in the previous year. They were randomized to receive placebo (n=87), 10 mg of brensocatib (n=82), or 25 mg of brensocatib (n=87) once daily for 24 weeks in the ratio of 1:1:1.
The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed.
Key findings of the study include:
- The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group.
- Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo.
- The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 in the 10-mg group and 0.62 in the 25-mg group.
- The incidence-rate ratio was 0.64 in the 10-mg group, as compared with placebo, and 0.75 in the 25-mg group, as compared with placebo.
- With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period.
- The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.
"In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes," concluded the authors.
"Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis," is published in the New England Journal of Medicine.
DOI: https://www.nejm.org/doi/full/10.1056/NEJMoa2021713
