Brensocatib is an oral medication under investigation for the treatment of non-cystic fibrosis bronchiectasis, a chronic lung disorder in which inflammation driven by elevated levels of neutrophil elastase can increase the risk of infection and cause frequent pulmonary exacerbations.

Using data from a phase I study conducted in healthy adult volunteers and a phase II study in adults with non-cystic fibrosis bronchiectasis, a population pharmacokinetic model was developed to describe the pharmacokinetics of brensocatib; additionally, the pharmacokinetic/pharmacodynamic relationships for inhibition of neutrophil elastase, reduction in pulmonary exacerbations, and incidence of adverse events were evaluated.

A threshold of brensocatib exposure that resulted in sputum neutrophil elastase levels below the level of quantification was identified, a strong relationship between such undetectable sputum neutrophil elastase levels and a reduction in pulmonary exacerbations was found, and no significant trend between brensocatib exposure and adverse events of special interest (periodontal disease, hyperkeratosis, and infections other than pulmonary infections) was detected.