Brensocatib Side Effects: FDA-Approved Oral Therapy for Non-Cystic Fibrosis Bronchiectasis

Brinsupri, marketed under the brand name Brensocatib, represents a major advance in respiratory medicine. In August 2025, the US Food and Drug Administration (FDA) approved this first-in-class oral drug for the treatment of non-cystic fibrosis bronchiectasis (NCFB) – a chronic, inflammatory lung condition that has long lacked targeted treatment options.

This approval is an important step in addressing the persistent airway inflammation associated with NCFB. However, as with all medicines, understanding the Brensocatib side effects, mechanism of action, and clinical benefits of brinsupri is essential for safe and effective use.

What is Brensocatib (Brinsupri)?

Brensocatib (Brinsupri) is an oral dipeptidyl peptidase-1 (DPP-1) inhibitor developed for the treatment of non-cystic fibrosis bronchiectasis. This condition is characterized by chronic bacterial infection and excessive inflammation, leading to airway damage, persistent cough, and frequent exacerbations. Unlike other treatments that focus on symptom control, Brensocatib targets the underlying inflammatory pathway – providing a disease-modifying approach rather than just providing relief.

Mechanism of Action: How Brensocatib Works

Brensocatib works by inhibiting DPP-1 (dipeptidyl peptidase-1), an enzyme responsible for activating neutrophil serine proteases (NSPs), such as elastase, proteinase 3, and cathepsin G. When overproduced, these enzymes cause lung tissue destruction and airway inflammation in patients with bronchiectasis.

By blocking DPP-1, Brensocatib effectively reduces the activation of these harmful enzymes, which leads to:

• reduced airway inflammation,

• reduced lung tissue damage, and

• reduced frequency of disease exacerbations.

This mechanism provides a novel anti-inflammatory strategy that directly targets the biological drivers of NCFB.

FDA Approval and Clinical Milestones

The FDA’s August 2025 approval of Brensocatib was based on robust data from phase 3 clinical trials evaluating its efficacy and safety in adults with NCFB.

🔹 Key Clinical Trial Highlights:

• Study Name: WILLOW-3 Trial
• Participants: Over 500 adults diagnosed with non-cystic fibrosis bronchiectasis.
• Duration: 52 weeks
• Primary Endpoint: Reduction in frequency of pulmonary exacerbations.
• Results: Patients receiving Brensocatib showed a significant decrease in exacerbation rate compared with placebo.
• Safety: The drug was generally well tolerated, but Brensocatib side effects were observed, especially related to the respiratory and gastrointestinal systems.

The FDA granted standard approval to Brensocatib following positive trial outcomes demonstrating clinical benefit and manageable side effect profile.

Dosage and Administration

Brensocatib is formulated as an oral tablet and is typically prescribed as a once-daily dose. The exact dose may vary based on individual patient factors, including:

• Severity of disease
• Co-existing medical conditions
• Concomitant medications

It should be taken with water at the same time each day, and patients are advised to continue regular check-ups to monitor therapeutic response and side effects.

Note: Brensocatib should not be self-administered without a healthcare provider’s guidance.

Brensocatib Side Effects: What You Need to Know

While Brensocatib has shown strong clinical benefits, understanding its side effects is vital to ensure safe use. The most common Brensocatib side effects observed during clinical trials include:

1. Respiratory System Side Effects

• Cough
• Sore throat
• Shortness of breath
• Exacerbation of underlying lung conditions

Because Brensocatib targets neutrophil enzymes, minor disturbances in immune defense can temporarily increase the risk of mild respiratory infections.

2. Gastrointestinal Side Effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea

These side effects are generally mild to moderate and often resolve as the body adjusts to the treatment.

3. Headache and Fatigue

Some patients have reported headaches, fatigue, and dizziness. These effects may result from mild inflammation reduction and systemic enzyme modulation.

4. Oral and Dental Effects

Due to DPP-1 inhibition in oral tissues, a few patients experienced:

• Gum irritation
• Mouth ulcers
• Tooth sensitivity

Maintaining good oral hygiene can help mitigate these Brensocatib side effects.

5. Skin and Allergic Reactions

Although rare, hypersensitivity reactions such as rash, itching, or swelling may occur.
Patients should immediately seek medical attention if they experience signs of severe allergic response, such as:

• Swelling of the face or throat
• Difficulty breathing
• Severe rash or hives

6. Laboratory Abnormalities

Some patients may show mild changes in laboratory values, including:

• Elevated liver enzymes (ALT/AST)
• Mild leukopenia (low white blood cell count)

These abnormalities are typically reversible and do not require treatment discontinuation in most cases.

Brensocatib Side Effects vs. Benefits

When evaluating Brensocatib side effects, it is important to balance them against the therapeutic benefits it offers. For patients suffering from frequent bronchiectasis flare-ups, this medication significantly improves:

• Lung function
• Quality of life
• Frequency of exacerbations
• Overall disease management

Most side effects are manageable and tend to decrease over time with continuous therapy and medical supervision.

Precautions and Warnings

Before starting Brensocatib, patients should inform their healthcare provider about:

• Liver disease or abnormal liver tests
• Ongoing infections
• Use of other anti-inflammatory or immunosuppressive medications
• Pregnancy or breastfeeding status

Because Brensocatib may slightly affect immune function, live vaccines should be avoided during treatment unless specifically advised by a healthcare professional.

Drug Interactions

Brensocatib may interact with certain medications, including:

• Antibiotics (macrolides, fluoroquinolones)
• Antifungals
• Immunosuppressants
• CYP3A4 inhibitors or inducers

Such interactions can affect how Brensocatib is metabolized, potentially increasing the risk of side effects or reducing effectiveness.
A healthcare professional should review all medications before starting therapy.

Use in Special Populations

📍 Pregnancy and Lactation

There is limited clinical data on Brensocatib use during pregnancy or breastfeeding. It should be prescribed only when potential benefits justify potential risks.

📍 Geriatric Patients

Older adults may require careful monitoring for Brensocatib side effects due to slower metabolism and co-existing diseases.

📍 Pediatric Use

Safety and effectiveness in children have not been fully established.

Clinical Benefits of Brensocatib in NCFB

Beyond managing symptoms, Brensocatib represents a disease-modifying approach for non-cystic fibrosis bronchiectasis.
Key benefits include:

1. Reduced inflammation in airways.
2. Lower risk of flare-ups and infections.
3. Improved lung function and oxygenation.
4. Enhanced quality of life by minimizing coughing and mucus production.
5. Long-term disease control through DPP-1 enzyme inhibition.

These benefits have made Brensocatib a pioneering treatment and a cornerstone in modern bronchiectasis management.

Monitoring During Brensocatib Therapy

Patients receiving Brensocatib should undergo periodic evaluations, including:

• Liver function tests
• Complete blood counts
• Respiratory function assessments

Early monitoring helps detect potential Brensocatib side effects before they progress into complications.

Patient Experience and Real-World Impact

Early post-approval data and patient feedback highlight notable symptom relief, including:

• Fewer flare-ups
• Improved breathing capacity
• Better exercise tolerance

Most patients tolerate Brensocatib well, and side effects are transient or mild compared to its clinical benefits.

Research Outlook: The Future of DPP-1 Inhibitors

The approval of Brensocatib marks only the beginning of DPP-1–targeted therapies. Researchers are exploring its potential for:

• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Other neutrophilic inflammatory disorders

Such ongoing trials may expand Brensocatib’s therapeutic landscape beyond NCFB, paving the way for a new generation of anti-inflammatory respiratory drugs.

Conclusion

Brensocatib (Brinsupri) stands out as a novel oral treatment for non-cystic fibrosis bronchiectasis, offering a targeted approach to chronic airway inflammation.

Its DPP-1 inhibition mechanism directly targets the root cause of lung damage, improving respiratory health and reducing disease severity.

Brensocatib can cause side effects such as cough, nausea, headache and mild elevations in liver enzymes, but these are usually manageable and reversible.

When used under appropriate medical guidance, the benefits of Brensocatib far outweigh its risks, making it a promising breakthrough for patients seeking to improve long-term respiratory health.

FAQs about Brensocatib Side Effects