Brensocatib: The First FDA-Approved Treatment for Non-Cystic Fibrosis Bronchiectasis

Brensocatib, recently approved by the FDA under the brand name Brinsupri, is the first disease-modifying therapy for non-cystic fibrosis bronchiectasis (NCFB). Unlike traditional symptom-relief treatments, Brensocatib targets the underlying cause of lung inflammation by inhibiting dipeptidyl peptidase 1 (DPP1), reducing neutrophil serine protease activity. Clinical trials (WILLOW and ASPEN) have shown significant improvements in lung function, reduced exacerbations, and better quality of life. Approved for patients aged 12 and older, Brensocatib represents a paradigm shift in chronic respiratory care. Its future use may extend to cystic fibrosis, asthma, and COPD. As a first-in-class DPP1 inhibitor, Brensocatib is poised to lead the next generation of targeted pulmonary therapies.

Introduction to Brensocatib: A New Era in Respiratory Treatment

Brensocatib is emerging as a revolutionary treatment for non-cystic fibrosis bronchiectasis (NCFB), a chronic lung condition characterized by repeated infections, persistent coughing, and progressive airway damage. Approved by the U.S. Food and Drug Administration (FDA) in August 2025, Brensocatib—marketed under the brand name Brinsupri—is the first and only therapy specifically indicated for adults and adolescents (12 years and older) living with NCFB.

Bronchiectasis, especially the non-cystic fibrosis type, has long lacked disease-modifying treatments. Patients often rely on antibiotics, steroids, and airway clearance therapies, which address symptoms but not the underlying inflammation. Brensocatib changes that narrative by targeting the neutrophilic inflammation responsible for much of the lung damage in this disease.

Developed by Insmed Inc., Brensocatib represents a novel class of drugs that work by inhibiting dipeptidyl peptidase 1 (DPP1), an enzyme critical for activating harmful neutrophil serine proteases. These proteases contribute to inflammation and tissue degradation in the lungs. By reducing their activation, Brensocatib addresses the root cause of exacerbations and lung decline in NCFB.

With robust data from Phase 2 and 3 trials showing reduced exacerbation rates and improved lung function, Brensocatib is now positioned as a game-changer in respiratory medicine. It’s not just a treatment—it’s a signal that innovation in chronic lung diseases is gaining momentum.

For patients, caregivers, and clinicians, the arrival of Brensocatib opens new possibilities for personalized, targeted care that goes beyond managing symptoms.

How Brensocatib Works: A New Target in Airway Inflammation

Brensocatib’s innovation lies in its ability to interrupt a core pathway of inflammation in the lungs. Unlike traditional treatments that manage symptoms, Brensocatib targets the underlying mechanism driving lung damage in non-cystic fibrosis bronchiectasis (NCFB): the excessive activity of neutrophil serine proteases (NSPs).

Neutrophils are a type of white blood cell responsible for defending the body against infections. However, in diseases like bronchiectasis, their overactivation causes damage to lung tissues. These destructive effects are largely due to NSPs, including elastase, cathepsin G, and proteinase-3, which break down healthy lung tissue during chronic inflammation.

Brensocatib works by inhibiting dipeptidyl peptidase 1 (DPP1), the enzyme responsible for activating these NSPs inside neutrophils before they are released into the bloodstream. By blocking DPP1, Brensocatib prevents neutrophils from becoming overly destructive, thereby reducing inflammation, slowing lung function decline, and decreasing exacerbations.

This approach is considered first-in-class, meaning Brensocatib is the first approved drug to use this mechanism. It has a reversible and selective binding profile, offering a targeted way to modulate immune activity without broadly suppressing immune function.

In both the WILLOW and ASPEN trials, patients treated with Brensocatib showed significant reductions in exacerbation rates, and improvements in lung health markers such as FEV₁ and QOL-B scores. These clinical outcomes support the mechanism’s relevance and pave the way for future use in other inflammatory lung diseases.

Clinical Trials and Effectiveness of Brensocatib

The clinical success of Brensocatib is backed by two major trials—WILLOW and ASPEN—which evaluated its efficacy in reducing lung inflammation and improving outcomes for patients with non-cystic fibrosis bronchiectasis (NCFB).

The WILLOW Trial (Phase 2)

This early-stage study laid the foundation for Brensocatib’s development. Patients treated with 10 mg and 25 mg of Brensocatib daily showed a statistically significant increase in time to first exacerbation compared to placebo. There were also marked reductions in neutrophil elastase activity—an important biomarker for disease progression.

The ASPEN Trial (Phase 3)

As the pivotal study leading to FDA approval, the ASPEN trial enrolled over 1,600 patients globally. It confirmed that Brensocatib reduced the annualized rate of pulmonary exacerbations, improved lung function (measured by FEV₁), and enhanced quality of life scores (QOL-B RSS) compared to placebo. These benefits were most prominent at the 25 mg dose, though the 10 mg dose also showed significant effects.

Additionally, patients taking Brensocatib demonstrated slower lung function decline, especially those with eosinophilic phenotypes or those not on long-term macrolide therapy.

Importantly, both trials showed that Brensocatib is well-tolerated, with a safety profile comparable to placebo. Most side effects were mild to moderate, including headache, diarrhea, and upper respiratory infections.

Overall, these trials solidify Brensocatib as the first disease-modifying therapy for NCFB, addressing both inflammation and clinical symptoms.

Who Can Benefit from Brensocatib?

Brensocatib offers new hope to individuals suffering from non-cystic fibrosis bronchiectasis (NCFB)—a chronic lung disease marked by repeated infections, inflammation, and irreversible airway damage. Until now, patients with NCFB had no disease-modifying treatment options, relying mostly on symptom management with antibiotics, bronchodilators, or mucolytics.

Approved in August 2025 under the brand name Brinsupri, Brensocatib is indicated for adults and adolescents aged 12 and older who experience frequent exacerbations despite standard care. It is particularly beneficial for those who have:

Neutrophilic airway inflammation

Two or more exacerbations per year

Declining lung function (FEV₁)

Poor quality of life due to coughing, sputum, and fatigue

Who Should Consider Brensocatib?

Patients not responding to long-term macrolide therapy

Individuals with elevated neutrophil serine protease activity

Adolescents with confirmed NCFB and persistent symptoms

Patients seeking a preventive, anti-inflammatory approach rather than reactive care

Who Should Use Caution?

While generally well-tolerated, Brensocatib may not be suitable for:

Pregnant or breastfeeding individuals

Patients with a history of immunosuppression

Those with liver or kidney impairments, until further data is available

Future Indications

Brensocatib is under investigation for other neutrophil-driven diseases, including:

Cystic fibrosis (CF)

Severe asthma

Chronic obstructive pulmonary disease (COPD)

Its selective mechanism of action positions it as a potential platform therapy for chronic lung inflammation.

The Future of Respiratory Care with Brensocatib

The approval of Brensocatib (Brinsupri) marks a transformative moment in respiratory medicine—particularly for non-cystic fibrosis bronchiectasis (NCFB), a disease long underserved by pharmaceutical innovation. But beyond its current indication, Brensocatib is paving the way for a new era of targeted anti-inflammatory therapies for lung diseases.