Brensocatib for bronchiectasis delivers in phase II trial

07 Nov 2020

Suppressing neutrophil serine protease activity with brensocatib appears to benefit patients with bronchiectasis, yielding improvements in clinical outcomes, according to the results of a phase II study.

In total, 256 patients (mean age, 64 years; 68 percent female) were randomized to receive placebo (n=87) or brensocatib 10 mg (n=82) or 25 mg (n=87) once daily for 24 weeks. The baseline concentration of neutrophil elastase in sputum was below the lower limit of quantification in more than 20 percent of the participants across the treatment arms.

Active treatment prolonged the time to the first exacerbation, the primary study endpoint, relative to placebo (25th percentile of the time to the first exacerbation, 67 days on placebo vs 134 days on 10-mg brensocatib and 96 days on 25 mg; p=0.03 and p=0.04, respectively).

Cox analysis confirmed the beneficial effect of brensocatib on exacerbation (10 mg: hazard ratio [HR], 0.58, 95 percent confidence interval [CI], 0.35–0.95; p=0.03; 25 mg: HR, 0.62, 95 percent CI, 0.38–0.99; p=0.046).

The incidence rates of exacerbations were 1.37 per person-year in the placebo group, 0.88 per person-year in the 10-mg brensocatib group, and 1.03 per person-year in the 25-mg brensocatib group (incidence rate ratio vs placebo, 0.64, 95 percent CI, 0.42–0.98 in the 10-mg group and 0.75, 95 percent CI, 0.50–1.13 in the 25-mg group; p=0.04 and p=0.17, respectively).

Sputum neutrophil elastase activity decreased from baseline over the 24-week treatment period in the active treatment arms. Compared with placebo, the 10-mg and 25-mg brensocatib doses led to a higher incidence of dental and skin adverse events of special interest, respectively.

The present data underscore the clinical potential of directly reducing inflammation in patients with bronchiectasis.

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