Efficacy and Safety of Brensocatib in Participants of Asian Race with Non-cystic Fibrosis Bronchiectasis: A Subgroup Analysis of the ASPEN Trial

In the ASPEN trial, brensocatib, a dipeptidyl peptidase 1 inhibitor, significantly reduced the burden of pulmonary exacerbations versus placebo in participants with bronchiectasis. A prespecified subgroup analysis evaluated the efficacy and safety of brensocatib in participants of Asian race with bronchiectasis from ASPEN. Participants with confirmed bronchiectasis and a history of exacerbations in the 12 months before screening [adults (18–85 years), ≥ 2; adolescents (12– < 18 years), ≥ 1] received once-daily brensocatib (10 or 25 mg) or matching placebo for 52 weeks (adults, 1:1:1; adolescents, 2:2:1). Efficacy endpoints included annualized exacerbation rate, time to first exacerbation, and change at 52 weeks in post-bronchodilator (BD) forced expiratory volume (FEV) in 1 s (post-BD FEV1) and Quality of Life–Bronchiectasis Respiratory Symptom Score (QOL-B RSS). Safety was monitored from enrollment through the end of study. Overall, 191 participants were of Asian race (n = 63, brensocatib 10 mg; n = 64, brensocatib 25 mg; n = 64, placebo). Brensocatib 10 mg and brensocatib 25 mg significantly reduced the annualized exacerbation risk (both by ~ 60%; p = 0.0005 and p = 0.0012, respectively) and prolonged the time to first exacerbation (hazard reduced by ~ 55%; p = 0.0039 and 0.0082, respectively) versus placebo. Brensocatib 25 mg significantly reduced post-BD FEV1 decline [least squares mean difference (95% CI): 69 (24–114) mL, p = 0.0029] and improved QOL-B RSS score [7.49 (2.48–12.50) points, p = 0.0034] versus placebo. The frequency of treatment-emergent adverse events was similar across treatment groups and consistent with the overall ASPEN results. In participants of Asian race, brensocatib 10 mg and 25 mg reduced the burden of pulmonary exacerbations, and the 25-mg dose reduced lung function decline and improved patient-reported symptoms versus placebo. The efficacy and safety of brensocatib in participants of Asian race were largely consistent with the overall ASPEN population, with select outcomes showing numerically greater benefit, although ASPEN was not powered to detect treatment differences in prespecified subgroup analyses. NCT04594369. Bronchiectasis is a long-term inflammatory lung disease that usually worsens over time. Brensocatib is a new medicine developed to treat bronchiectasis. In a clinical trial called ASPEN, people with bronchiectasis took brensocatib at doses of 10 mg or 25 mg or a placebo, for 52 weeks. In ASPEN, brensocatib reduced the number of exacerbations versus placebo. In this study, researchers wanted to know the effect of brensocatib in people of Asian race with bronchiectasis who took part in ASPEN. A total of 191 people of Asian race were assessed: 63 took brensocatib 10 mg, 64 took brensocatib 25 mg, and 64 took a placebo. During the study, both doses of brensocatib reduced the risk of people having an exacerbation by about 60% versus placebo and prolonged the time to their first exacerbation, reducing the chance of exacerbating by about 55%. Compared with placebo, the 25-mg dose reduced the decline in lung function caused by bronchiectasis and improved bronchiectasis symptoms as reported by the people themselves. The occurrence of side effects was similar among the people who took brensocatib and those who took placebo and was similar to the overall ASPEN clinical trial. In summary, brensocatib reduced the burden of exacerbations and improved lung function and the symptoms of bronchiectasis in people of Asian race from ASPEN, although the number of people was small. Generally, the benefits of brensocatib in people of Asian race were similar to those in the overall ASPEN clinical trial, and some benefits were numerically larger.