FDA Sets Review Date for Chronic Lung Disease Therapy

The FDA has accepted Insmed’s new drug application for brensocatib to treat patients with non-cystic fibrosis bronchiectasis. Regulators have granted priority review and have set a target action date of Aug. 12, 2025, under the Prescription Drug User Fee Act (PDUFA).

Bronchiectasis is a serious, chronic lung disease in which the bronchi become permanently dilated due to a cycle of infection, inflammation, and lung tissue damage. It results in frequent pulmonary exacerbations requiring antibiotic therapy and/or hospitalizations. Approximately 500,000 patients in the United States are currently diagnosed with bronchiectasis.

“Bronchiectasis is a chronic, progressive disease with no approved treatments, leaving hundreds of thousands of people in the U.S. without an effective way to reduce the pulmonary exacerbations that can lead to serious consequences, Martina Flammer, M.D., MBA, chief medical officer of Insmed, said in a news release.

If approved, brensocatib could be the first approved treatment for bronchiectasis and the first in a new class of medicines called dipeptidyl peptidase 1 (DPP1) inhibitors for the treatment of neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs) in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation.

In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation.

Insmed’s NDA is based on data from the phase 3 ASPEN study. The study met its primary endpoint with both dosage strengths of brensocatib achieving statistical and clinical significance. The primary efficacy analysis in ASPEN included data from 1,680 adult patients and 41 adolescent patients, and the primary endpoint was annualized rate of pulmonary exacerbations.

In a subset analysis from 19 pre-specified categories of patients, annualized rate of pulmonary exacerbations favored brensocatib at both the 10 mg and 25 mg doses over placebo. In a separate analysis, least squares mean difference for brensocatib 25 mg demonstrated a reduced decline in post-bronchodilator FEV1 at week 52 versus placebo for all prespecified subgroups. Results for patients treated with brensocatib 10 mg among subgroups were aligned with the overall trial population results. VEV1 is a common measure of airway obstruction

Treatment-emergent adverse events were more common in the brensocatib arms and included COVID-19, nasopharyngitis, cough, and headache.

Insmed is also conducting the phase 2b BiRCh trial of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and anticipates providing top-line data from the study in the second half of 2025. The company has also recently begun a phase 2 study of brensocatib in patients with hidradenitis suppurativa, a skin condition that causes abscesses and scarring.