Brensocatib in Bronchiectasis Patients: A Phase 2 Trial

Lungs, obese male
Lungs, obese male
Investigators examined whether brensocatib reduces incidence of exacerbations of bronchiectasis, reduces rate of exacerbations, or changes the concentration of active neutrophil in the sputum from baseline.

Brensocatib prolonged time to first exacerbation, lowered rates of exacerbation, reduced neutrophil serine protease activity, and was associated with improved clinical outcomes for patients with bronchiectasis, according to results from a phase 2 trial published in the New England Journal of Medicine.

Investigators conducted a randomized, double-blind, placebo-controlled trial ( number, NCT03218917) to examine whether brensocatib reduced the incidence of exacerbations of bronchiectasis. They randomized patients in a 1:1:1 ratio to receive either placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The primary endpoint was the time to first exacerbation during the 24-week treatment period. Secondary endpoints were rate of exacerbation, change in forced expiratory volume in 1 second after bronchodilator use from baseline, and change in concentration of active neutrophil in the sputum.

Of the 256 patients included in the study, 87 received placebo, 82 received 10 mg of brensocatib, and 87 received 25 mg of brensocatib. The median time to first exacerbation was 189 days for the placebo group, but could not be estimated for the 10 mg and 25 mg groups because of the low numbers of exacerbations. The time to first exacerbation was significantly longer with both 10 mg of brensocatib (P =.03) and 25mg (P =.04) compared with placebo. Sensitivity analyses found consistent results when patients who prematurely discontinued the trial were included.

In total, 32% of patients who received 10 mg of brensocatib and 33% of patients who received 25 mg of brensocatib had 1 or more exacerbations, significantly lower compared with 48% of patients who received placebo (P =.03; P =.04, respectively). The incidence rates of exacerbations in the placebo, 10 mg, and 25 mg groups were 1.37 exacerbations per person-year (PY), 0.88 exacerbations per PY, and 1.03 exacerbations per PY, respectively. The incidence-rate ratio was 0.64 in the 10 mg group and 0.75 in the 25mg group compared to placebo (P =.04; P =.17, respectively).

Sputum neutrophil activity was also reduced in both brensocatib groups compared with placebo. Both brensocatib groups also experienced higher dental and skin adverse events compared with placebo.

According to investigators, while the reduction of neutrophil proteases with brensocatib appears to offer clinical benefits, the findings cannot be considered clinically directive due to the trial’s short duration and limited enrollment. Investigators noted that the trial also lacked sufficient power to show differences in efficacy between the doses tested and it is unknown whether brensocatib can be given without an increased long-term risk of infection.

“[B]rensocatib prolonged the time to the first exacerbation and led to a lower frequency of exacerbations than placebo in patients with bronchiectasis,” the investigators concluded. This shows the potential clinical benefits of directly reducing inflammation in these patients.


Chalmers JD, Haworth CS, Metersky ML, et al; for the WILLOW Investigators. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2020;383(22):2127-2137. doi:10.1056/NEJMoa2021713