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Brensocatib, Potential First Treatment for Non-CF Bronchiectasis, Gets Priority Review
Brensocatib, also a potential first-in-class DPP1 inhibitor, has a PDUFA date of August 12, 2025.
The FDA has accepted and granted priority review to Insmed’s New Drug Application (NDA) for brensocatib, a potential first treatment for patients with non-cystic fibrosis bronchiectasis, with a Prescription Drug User Fee Act (PDUFA) of August 12, 2025.1
Brensocatib has the potential to be the first and only 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. Insmed also plans to file regulatory submissions for brensocatib in the EU, UK, and Japan in 2025, with commercial launches pending approval anticipated in 2026.
"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, MD, MBA, Chief Medical Officer of Insmed, said in a statement.1 "Brensocatib has the potential to transform the treatment landscape for bronchiectasis and we were pleased to receive the FDA acceptance of our NDA with Priority Review even earlier than anticipated. We look forward to working with the FDA throughout the review process and, pending approval, bringing the first ever bronchiectasis treatment to patients as quickly as possible."
The NDA submission was based on data from the landmark Phase 3 ASPEN study, which met its primary endpoint of clinically and statistically significantly reducing the annualized rate of pulmonary exacerbations compared with placebo over 52 weeks in both its 10 and 25 mg dosages. The ASPEN study was conducted in 391 sites in 35 countries and included 11680 adult (18 to 85 years of age) and 41 adolescent (12 to 17 years of age) patients randomized 2:2:1 to receive brensocatib 10 mg, brensocatib 25 mg, or placebo once daily for 52 weeks, followed by 4 weeks off treatment.
Both dosage groups also had significantly prolonged time to first exacerbation and significantly increased odds of remaining exacerbation-free over the study’s treatment period. Patients treated with brensocatib 25 mg also experienced significantly lower lung function decline at week 52 as measured by post-bronchodilator forced expiratory volume over one second.
Brensocatib was well-tolerated in the study. Common treatment-emergent adverse events (occurring in at least 5.0% of patients treated with either dose of brensocatib and more frequently than in placebo) in patients treated with for brensocatib 10 mg, brensocatib 25 mg, or placebo were COVID-19 (15.8%, 20.9%, and 15.8%, respectively), nasopharyngitis (7.7%, 6.3%, and 7.6%, respectively), cough (7.0%, 6.1%, and 6.4% respectively), and headache (6.7%, 8.5%, and 6.9% respectively).1
Other recent research into alpha-1 antitrypsin deficiency (AATD)-related lung disease, one cause of bronchiectasis, investigated associations with the disease among patients with different genotypes, namely PI*SS, PI*ZZ, and PI*SZ. The study, which leveraged data from the European Alpha-1 Antitrypsin Deficiency Research Collaboration (EARCO), found a lower risk of lung disease among patients with the PI*SS genotype compared to those with the PI*ZZ genotype, although no significant differences were observed compared to the PI*SZ genotype.2
“The risk for developing AATD-related emphysema is well established for the PI*ZZ genotype, and an increased risk has been demonstrated for PI*SZ, particularly in smokers,” Marc Miravitlles, MD, a pulmonologist and senior researcher at the Vall d’Hebron University Hospital and the Vall d’Hebron Research Institute in Spain, and colleagues wrote.2 “However, it remains unclear for other genotypes, such as PI*SS.”
REFERENCES
FDA Grants Priority Review to Insmed's Brensocatib for Treatment of Bronchiectasis with PDUFA Target Action Date Set for August 12, 2025. News release. Insmed. February 6, 2025. https://www.prnewswire.com/news-releases/fda-grants-priority-review-to-insmeds-brensocatib-for-treatment-of-bronchiectasis-with-pdufa-target-action-date-set-for-august-12-2025-302369466.html
Martín, T., Guimarães, C., Esquinas, C. et al. Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project. Respir Res 25, 260 (2024). https://doi.org/10.1186/s12931-024-02879-y
