The European Medicines Agency (EMA) has recommended granting marketing authorization in the EU for brensocatib (Brinsupri, Insmed Incorporated) for non-cystic fibrosis bronchiectasis (NCFB) in patients aged 12 and older with at least two flare-ups in the last 12 months. 

NCFB is a chronic, progressive lung disease caused by permanent bronchial dilation and inflammation. Symptoms include daily cough, sputum, and recurrent exacerbations, typically between one and four times per year. Exacerbations are linked to a progressive decline in lung function, lower quality of life, and higher mortality. 

The condition occurs mostly in elderly patients and may arise from factors including pneumonia, cilia abnormalities, and immune deficiencies. Estimates suggest that between 400,000 and three million people in Europe have NCFB. 

This is the first medicine to be recommended in Europe for NCFB. Patients currently rely on airway clearance, antibiotics, and anti-inflammatory medicines. 

The active substance in Brinsupri is brensocatib, which works by inhibiting DPP1, an enzyme that plays a role in activating neutrophils. Excessive activation of neutrophils leads to damage of airway walls, excess mucus, sustained inflammation, and reduced immune function. 

The EMA recommendation comes after a phase 3 randomized, double-blind, placebo-controlled clinical trial which involved 1721 patients aged 12 and older. Patients were treated with either 10 mg or 25 mg of brensocatib per day or a placebo.

At 52 weeks, the annualized rate of pulmonary exacerbation was 1.02 in the 10 mg group, 1.04 in the 25 mg group and 1.29 in the placebo group. The rate ratios were 0.79 and 0.81 for the 10 mg and 25 mg groups, respectively.

In each of the brensocatib groups, 48.5% of patients remained exacerbation-free at week 52 compared with 40.3% of those in the placebo group. Patients in the 25 mg group experienced a 14-week delay in the median time to first pulmonary exacerbation. 

Incidence of adverse events was similar across all groups, although those taking brensocatib were more likely to experience hyperkeratosis. Other common adverse events included headache, gingival and periodontal diseases, dermatitis, rash, upper respiratory tract infections, and dry skin. 

Use during pregnancy is not recommended, as animal studies demonstrate embryo-fetal toxicity. Brinsupri will be available as 25 mg film-coated tablets. 

The opinion will now be reviewed by the European Commission to decide upon EU-wide marketing authorization. 

Detailed recommendations for using Brinsupri will be described in the summary of product characteristics, which will be published on the EMA’s website in all official European Union languages.

Annie Lennon is a medical journalist. Her writing appears on Medscape, WebMD, and Medical News Today, among other outlets.