Abstract Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive, inflammatory lung disease defined by irreversibly damaged and dilated bronchi driven by neutrophil-mediated inflammation. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase-1, reduces neutrophilic inflammation and is approved by the Food and Drug Administration (FDA) for treatment of NCFB. Introduction We report here our experience of one patient who has been on brensocatib for 6 years, the longest known exposure. Case Description 70 year old woman with NCFB and Mycobacterium avium complex lung infection since 2008, treated unsuccessfully three times due to medication intolerance, history of gastroesophageal reflux disease and recurrent sinus infections. Symptoms included dyspnea on exertion (DOE) and severe fatigue.The patient was randomized into Willow, the brensocatib phase 2 trial, in February 2019. In the 12 months prior to enrollment, the patient had one pneumonia and 3 pulmonary exacerbations. During the 6-month treatment period of the trial, the patient did not have any pulmonary exacerbations. 3 months after randomization, the patient reported great improvement in symptoms with increased energy and ability to enjoy life. At Month 4, her DOE was much better and cough resolved. After the study was over, expanded access to study drug was requested and a single-patient Investigational New Drug application was submitted to the FDA. Within 6 weeks of re-starting drug, the patient began to feel better, had more energy and by 12 weeks was symptom free. For the next 2 years, she stayed exacerbation and symptom free. In April 2022, the patient noted abdominal bloating and mild lower extremity edema. Brensocatib dosing was reduced to every other day. Her symptoms resolved and the patient stayed exacerbation free until September 2023 when she developed increased fatigue and DOE and began to have almost monthly exacerbations, requiring an increase in brensocatib back to daily dosing. She tolerated daily dosing for 1 year with one pulmonary exacerbation. In March 2025 the abdominal bloating and dry, itchy skin recurred on full dose, so lower doses were tried. Since September, she has been on 5 days/week dosing, is exacerbation free and doing well. Her spirometry (see table 1) and CT scans have remained stable. Conclusion In our patient, treatment with brensocatib over a six-year period improved disease symptoms, resulted in stable spirometry and chest CT scans and led to years of being exacerbation free with minor side effects. Long-term use of brensocatib is safe and efficacious in reducing pulmonary exacerbations. This abstract is funded by: none
Lau et al. (Fri,) studied this question.