DPP-1 inhibitor brensocatib lowers exacerbation frequency in bronchiectasis: NEJM
Delhi: The administration of brensocatib in bronchiectasis patients improves clinical outcomes of the disease, suggests a recent study in the New England Journal of Medicine.
Brensocatib prolonged the time to the first exacerbation and led to a lower frequency of exacerbations than placebo in patients with bronchiectasis.
Bronchiectasis patients experience frequent exacerbations that are thought to be caused by neutrophil inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, is increased in the sputum of bronchiectasis patients and increases even more during exacerbations. Brensocatib (INS1007) inhibits dipeptidyl peptidase 1 (DPP-1) -- enzyme responsible for the activation of neutrophil serine proteases.
This phase 2, randomized, double-blind, placebo-controlled trial was performed by James D. Chalmers, Ninewells Hospital and Medical School, Dundee (J.D.C.), Scotland, and colleagues to determine the role of Brensocatib in the management of bronchiectasis patients.
256 patients with bronchiectasis who had had at least two exacerbations in the previous year were randomly assigned in the ratio of 1:1:1 to receive placebo (n=87), 10 mg of brensocatib (n=82), or 25 mg of brensocatib (n=87) once daily for 24 weeks.
The time to the first exacerbation (primary endpoint), the rate of exacerbations (secondary endpoint), 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 bronchiectasis patients 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.
