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The European Medicines Agency (EMA) has recommended marketing authorization in the European Union for Brensocatib, marketed as Brinsupri, to treat non-cystic fibrosis bronchiectasis (NCFB) in patients aged 12 years and older with at least two exacerbations in the prior year. This approval marks the first authorized therapy specifically for NCFB in Europe, a chronic and progressive lung disease characterized by damaged airways, persistent cough, excessive mucus, and repeated lung infections leading to lung function decline and increased mortality.
Key Findings and Clinical Evidence
The EMA’s Committee for Medicinal Products for Human Use (CHMP) based its positive opinion on robust data from the phase 3 ASPEN trial, a randomized, double-blind, placebo-controlled study involving 1,721 patients aged 12 and above. The study demonstrated that patients treated with Brensocatib 25 mg once daily had a statistically significant 19% reduction in annualized exacerbation rates compared to placebo (rate ratio 0.81, 95% CI 0.69–0.94). Exacerbations—episodes of worsened respiratory symptoms—are critical disease milestones linked to progressive lung damage and worsened quality of life in NCFB.
Brensocatib works by inhibiting dipeptidyl peptidase 1 (DPP1), an enzyme essential for activating neutrophil serine proteases (NSPs) involved in the inflammatory process. Neutrophils, a type of white blood cell, release these proteases excessively in NCFB, causing airway wall damage, inflammation, and mucus overproduction. By blocking DPP1, Brensocatib reduces NSP activation, aiming to slow disease progression and improve lung function.
Expert Commentary
James Chalmers, MBChB, PhD, Professor and Consultant Respiratory Physician at the University of Dundee and lead investigator of the ASPEN study, commented: “Non-cystic fibrosis bronchiectasis is a progressive disease that can lead to lung function decline—and with diagnoses rising steadily worldwide, there is an urgent need for additional treatment options. Based on the clinical benefits demonstrated in the ASPEN and WILLOW studies, brensocatib has the potential to change the treatment paradigm in non-cystic fibrosis bronchiectasis, offering the prospect of significantly improving treatment outcomes for those living with this debilitating illness.”
Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed (the drug’s manufacturer), highlighted the significance of this milestone: “For too long, patients have had to endure the daily burden of this disease without a treatment specifically developed to treat bronchiectasis. This important milestone brings us one step closer to potentially bringing the first-ever approved treatment to NCFB patients in Europe.”
Context and Public Health Implications
NCFB is an under-recognized and heterogeneous respiratory condition affecting an estimated 400,000 to 3 million people in the EU. It arises from multiple causes, including previous respiratory infections, immune deficiencies, and structural airway abnormalities. The disease manifests most often in older adults and involves chronic inflammation and infection of the bronchi leading to permanent airway dilation.
Until now, treatment has focused primarily on managing symptoms through airway clearance techniques, antibiotics to control infections, and anti-inflammatory drugs, without any therapy approved to modify the disease course directly. The introduction of Brensocatib represents a significant advancement by targeting the inflammatory mechanism underlying disease progression.
Limitations and Considerations
While the ASPEN trial results were promising, noted adverse reactions to Brensocatib include headache, skin issues such as dermatitis and hyperkeratosis, oral gum disorders, and upper respiratory tract infections. Use in pregnancy is not recommended due to observed reproductive toxicity in animal studies. Long-term safety and efficacy data will require continued monitoring post-approval.
Some experts emphasize the need to consider individual patient variability in disease severity and response to treatment. Additionally, as NCFB is a complex disorder often accompanied by other comorbidities, integrated care approaches remain critical.
Practical Implications for Patients
For patients and healthcare providers, Brensocatib offers the first targeted orally administered therapy aiming to reduce exacerbation frequency and potentially preserve lung function. Patients with a history of frequent flare-ups (two or more in the past year) who are 12 years or older may benefit from this treatment once available in Europe. However, patients should continue to follow individualized management plans including airway clearance and infection control measures.
Final regulatory approval by the European Commission is expected in the coming months, following which Brensocatib will become an accessible treatment option, marking a new chapter in NCFB care.
Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
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