- Novel reversible dipeptidyl peptidase 1 (DPP1) inhibitor brensocatib significantly prolonged the time to the first exacerbation and reduced the risk for exacerbation in patients with noncystic fibrosis bronchiectasis.
- Annualized rates of exacerbation were also lower than placebo.
Why this matters
- Findings highlight the importance of treating neutrophil-mediated inflammation in patients with bronchiectasis.
- Larger and longer-term trials are needed to determine the risks and benefits of brensocatib for bronchiectasis.
- In this phase 2 WILLOW trial, 256 patients with bronchiectasis who had at least 2 exacerbations over the previous year were randomly assigned in a 1:1:1 ratio to receive 10 mg of brensocatib, 25 mg of brensocatib, or placebo, once daily for 24 weeks.
- Primary endpoint: time to first bronchiectasis exacerbation; secondary endpoints: rate of exacerbations and change in sputum neutrophil elastase (NE) activity.
- Funding: Insmed.
- Brensocatib significantly prolonged time to the first exacerbation over 24 weeks vs placebo (brensocatib 10 mg, P=.03; brensocatib 25 mg, P=.04).
- The risk for exacerbation was reduced with brensocatib vs placebo:
- brensocatib 10 mg: adjusted HR (aHR), 0.58; 95% CI, 0.35-0.95; P=.03; and
- brensocatib 25 mg: aHR, 0.62; 95% CI, 0.38-0.99; P=.046.
- The incidence rate ratio for brensocatib vs placebo was 0.64 (95% CI, 0.42-0.98; P=.04) in the 10-mg group and 0.75 (95% CI, 0.50-1.13; P=.17) in the 25-mg group.
- During the 24-week treatment period, the mean concentrations of NE in sputum were lower with both brensocatib doses vs placebo.
- Results were consistent among subgroups based on age, baseline NE concentrations, prior exacerbation history, bronchiectasis severity index, and lung function.
- The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, vs placebo.
- Relatively small sample size.
- Short trial duration.
Lead author James Chalmers, MBChB, PhD, said: “These results are critically important given the lack of approved pharmaceutical therapies to reduce the risk of exacerbation—the major driver of morbidity and mortality in patients with bronchiectasis. The results also validate the novel mechanism of action of brensocatib and highlight the potential benefits of reducing neutrophil serine protease activity."