Jordana Jampel

DocwireNews

In a phase 3, double-blind trial, researchers tested whether the dipeptidyl peptidase 1 (DPP-1) inhibitor brensocatib targets the key mediator of neutrophilic inflammation caused by bronchiectasis.Results were <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2411664">published</a> in The New England Journal of Medicine.The researchers randomly assigned patients (1,721 total; 1,680 adults in a 1:1:1 ratio and 42 adolescents in a 2:2:1 ratio) to receive brensocatib 10 mg or 25 mg once per day or placebo.The study&rsquo;s primary endpoint was the annualized rate of adjudicated pulmonary exacerbations over 52 weeks.Secondary endpoints included time to the first exacerbation during the 52-week period, the percentage of patients who remained exacerbation-free at 52 weeks, the change in forced expiratory volume in 1 second (FEV1), the annualized rate of severe exacerbations, and change in quality of life.The annual rate of pulmonary exacerbations was 1.02 in the 10-mg brensocatib group, 1.04 in the 25-mg brensocatib group, and 1.29 in the placebo group. The researchers calculated that there was a 21% reduction in exacerbation rate with 10 mg (rate ratio [RR], 0.79; 95% CI, 0.68-0.92; P=0.004) and a 19% reduction with 25 mg (RR, 0.81; 95% CI, 0.69-0.94; P=0.005) compared to placebo.The hazard ratio for time to first exacerbation was 0.81 for the 10-mg group (P=0.02) and 0.83 for the 25-mg group (P=0.04), indicating a delayed onset of exacerbations with treatment.By week 52, 48.5% of patients in both brensocatib dose groups remained free of exacerbations, compared to 40.3% in the placebo group (10 mg: RR, 1.20; 95% CI, 1.06-1.37; adjusted P=0.02 and 25 mg: RR, 1.18; 95% CI, 1.04-1.34; adjusted P=0.04).By week 52, FEV&#8321; had decreased by 50 mL in the 10-mg group, 24 ml in the 25-mg group, and 62 ml in the placebo group. Compared to placebo, the difference in FEV&#8321; decline was 11 ml with 10 mg (95% CI, -14 to 37; P=0.38) and 38 ml with 25 mg (95% CI, 11-65; P=0.04), indicating a statistically significant benefit only with the 25-mg dose.The overall incidence of adverse events was similar between groups, though hyperkeratosis was more common among patients receiving brensocatib.&ldquo;Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1&nbsp;was less with the 25-mg dose of brensocatib than with placebo,&rdquo; the researchers concluded.ReferenceChalmers JD, et al. N Engl J Med. 2025;392(16):1569-1581. doi:<a href="https://pubmed.ncbi.nlm.nih.gov/40267423/">10.1056/NEJMoa2411664</a>

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Brensocatib Shows Positive Results for Managing Bronchiectasis Symptoms

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Both 10-mg and 25-mg doses proved efficacy in lower rates of pulmonary exacerbations. 

Brensocatib Shows Positive Results for Managing Bronchiectasis Symptoms 

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