FDA Approval: 2025 | A First-in-Class DPP1 Inhibitor

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disease marked by recurrent infections, mucus overproduction, and persistent airway inflammation—primarily driven by dysregulated neutrophil activity. Until recently, treatment options remained limited to antibiotics, airway clearance therapies, and symptom-focused management.

In 2025, the FDA approved BRINSUPRI™ (brensocatib)—the first medication of its kind that targets the underlying neutrophil-mediated inflammatory pathway. This marks a significant advancement in the long-awaited therapeutic landscape for NCFB.

This article provides a comprehensive, clinician-focused review of BRINSUPRI’s mechanism, indications, dosing, safety profile, and clinical considerations.

What Is BRINSUPRI?

BRINSUPRI™ (brensocatib) is an oral DPP1 (dipeptidyl peptidase 1) inhibitor, approved for:

Indication

• Treatment of non-cystic fibrosis bronchiectasis

• Adults and pediatric patients aged 12 years and older

BRINSUPRI is the first and only DPP1 inhibitor approved for NCFB, offering a disease-modifying approach rather than symptomatic relief alone.

How BRINSUPRI Works (Mechanism of Action)

Neutrophils play a central role in airway destruction in NCFB. As they mature in the bone marrow, a key enzyme—DPP1—activates several neutrophil serine proteases (NSPs) that drive inflammation.

BRINSUPRI inhibits DPP1, leading to reduced activation of NSPs, including:

• Neutrophil elastase

• Cathepsin G

• Proteinase 3

Why This Matters

Activated NSPs damage airway tissue, promote mucus hypersecretion, worsen infections, and amplify chronic inflammation. By blocking DPP1, BRINSUPRI reduces the destructive potential of neutrophils.

This mechanism makes BRINSUPRI the first treatment to specifically interrupt the neutrophil-mediated inflammatory cycle in NCFB.

Who Should Use BRINSUPRI?

Approved For:

• Adults with NCFB

• Adolescents 12 years and older

• Patients with chronic symptoms, recurrent exacerbations, or mucus-related airway disease

Not Indicated For:

• Cystic fibrosis bronchiectasis

• Immunocompromised states related to bone marrow disorders

• Use with live attenuated vaccines (see precautions below)

Dosing and Administration

BRINSUPRI is simple to use:

Recommended Dose

• 10 mg orally once daily
  OR

• 25 mg orally once daily

• Can be taken with or without food

• Tablets available in 10 mg and 25 mg strengths

Missed Dose

• Skip the missed dose

• Take the next dose at the usual time

• Do NOT double the dose

This once-daily regimen improves patient adherence—important in a chronic condition like NCFB.

Safety Profile, Warnings & Precautions

While BRINSUPRI is generally well tolerated, clinicians should be aware of several key adverse effects.

1. Dermatologic Reactions

BRINSUPRI increases the risk of:

• Rash

• Dry skin

• Hyperkeratosis

Recommendations

• Monitor for new skin conditions

• Refer to dermatology if persistent or unexplained

• Encourage use of gentle skincare products

2. Gingival and Periodontal Adverse Reactions

Increased risk of:

• Gum inflammation

• Periodontal disease

• Gingival tenderness or swelling

Recommendations

• Ensure regular dental checkups

• Advise strict oral hygiene

• Early referral to dental services if symptoms develop

3. Avoid Live Attenuated Vaccines

Because the effects of BRINSUPRI on vaccine safety/effectiveness are unknown:

• Avoid live attenuated vaccines during treatment

• Examples include: MMR, varicella, intranasal influenza, yellow fever

Inactivated vaccines are generally considered safe.

Most Common Adverse Reactions (Incidence >2%)

• Upper respiratory tract infection

• Headache

• Rash

• Dry skin

• Hyperkeratosis

• Hypertension

These events were generally mild to moderate but require monitoring.

Contraindications

• None identified

This makes BRINSUPRI broadly accessible to a wide range of patients.

Role of BRINSUPRI in NCFB: Why This Approval Matters

Bronchiectasis remains a highly symptomatic and debilitating condition with few targeted therapies. The approval of BRINSUPRI creates a paradigm shift in management.

Key Benefits

• Addresses neutrophil overactivation, a core driver of disease

• Reduces airway inflammation

• Potential to decrease severity and frequency of exacerbations

• Suitable for long-term daily use

• Approved for both adults and adolescents (12+)

As further real-world data emerges, BRINSUPRI may reshape how clinicians manage NCFB, particularly in patients with recurrent exacerbations or persistent inflammation despite optimal therapy.

Clinical Considerations Before Prescribing BRINSUPRI

Evaluate:

• Baseline skin condition

• Dental health status

• Vaccination schedule

• Risk factors for hypertension

• Coexisting airway infections

Educate Patients About:

• Proper dental hygiene

• Avoiding live vaccines

• Watching for skin changes

• Adherence to once-daily dosing

• Not doubling doses if missed

Conclusion

BRINSUPRI™ (brensocatib) is a first-in-class DPP1 inhibitor designed to target neutrophil-driven inflammation at its source. With its 2025 FDA approval, it offers a long-awaited, disease-modifying therapy for adults and adolescents with non-cystic fibrosis bronchiectasis.

By modulating neutrophil protease activity, BRINSUPRI addresses a previously untreatable pathway—bringing new hope for patients suffering from chronic cough, exacerbations, and mucus-related breathing difficulties.