FDA Approves First-Ever DPP1 Inhibitor Brensocatib for Bronchiectasis Treatment

On August 12, 2025, Insmed announced that the FDA has officially approved its DPP1 inhibitor, brensocatib, for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) in patients aged 12 years and older.

This marks the arrival of the first targeted therapy in this disease area, filling a long-standing gap in effective treatments for patients.

Developed by Insmed, brensocatib is an oral, selective, competitive, and reversible dipeptidyl peptidase 1 (DPP1) inhibitor. It works by blocking DPP-1, thereby preventing the activation of neutrophil serine proteases (NSPs) and reducing neutrophil-mediated inflammation. It is indicated for bronchiectasis, chronic rhinosinusitis without nasal polyps (CRSsNP), and other neutrophil-driven diseases.

In October 2016, Insmed entered into an agreement with AstraZeneca to obtain global exclusive rights to develop and commercialize brensocatib. In February 2025, the FDA accepted Insmed’s New Drug Application (NDA) for brensocatib in NCFBE and granted priority review status. The approval was based on positive results from Insmed’s ASPEN Phase III clinical trial.

The ASPEN Phase III trial was a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of brensocatib in NCFBE patients. It enrolled more than 1,680 patients with a 48-week follow-up, making it the largest study of its kind to date. Full trial results were published in The New England Journal of Medicine (NEJM).

Over the 52-week treatment period, both brensocatib doses achieved statistically and clinically significant reductions in the annualized rate of pulmonary exacerbations compared to placebo. The annualized exacerbation rates were 1.02 for the 10 mg group, 1.04 for the 25 mg group, and 1.29 for placebo. The rate ratios versus placebo were 0.79 (adjusted p = 0.004) for 10 mg and 0.81 (adjusted p = 0.005) for 25 mg.

Additionally, both doses significantly prolonged the time to first exacerbation and increased the proportion of patients without exacerbations. Brensocatib was generally well tolerated.

As the first approved DPP1 inhibitor, brensocatib introduces an entirely new mechanism of action—not only improving outcomes for bronchiectasis patients but also potentially benefiting multiple neutrophil-driven inflammatory diseases.

Recently, Fosun Pharma licensed the overseas rights to its oral DPP1 inhibitor XH-S004 to U.S.-based Expedition Therapeutics for $645 million. XH-S004 is currently in Phase II clinical trials for bronchiectasis and Phase Ib for COPD in China. Domestic pharmaceutical companies are also accelerating their pipelines: Hisun’s HSK31858 has entered Phase III for bronchiectasis and received approval for COPD clinical trials, while Hengrui Pharma’s DPP1 inhibitor is in Phase Ib, mainly targeting COPD and other inflammatory diseases. These developments show that DPP1 has become a new hot target in respiratory disease treatment, promising more therapeutic options for patients in the future.