The MHRA has licensed brensocatib (Brinsupri, Insmed Netherlands B.V.) as the first targeted therapy specifically for non- cystic fibrosis bronchiectasis (NCFB), offering a new treatment option for patients aged 12 years or older who have had two or more pulmonary exacerbations within the previous year. 

The approval marks a milestone for this chronic respiratory condition, which previously had no disease-specific licensed therapies in the UK.

Targeting Lung Inflammation

NCFB is characterised by irreversibly damaged and dilated airways, leading to persistent cough with mucus production, recurrent infections, and progressive lung function decline. The condition affects individuals across all age groups but occurs more frequently in older adults. 

Until now, management has relied primarily on symptomatic treatments and antibiotics for exacerbations, with no therapies specifically licensed for the underlying disease pathophysiology.

Brensocatib is an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), a protein involved in pulmonary inflammation. The medicine works by blocking DPP-1 activity, thereby preventing activation of neutrophil serine proteases — key mediators of neutrophilic inflammation in bronchiectasis. This targeted approach aims to reduce pulmonary exacerbations and may also alleviate certain symptoms associated with NCFB.

Exacerbation Reduction

The approval was supported by evidence from the phase 2 WILLOW and phase 3 ASPEN clinical trials demonstrating significant reductions in exacerbation rates. 

In the ASPEN trial, 1721 patients (1680 adults and 41 adolescents) were randomised to receive brensocatib at 10 mg or 25 mg once daily, or placebo, over 52 weeks.

The primary endpoint was annualised rate of adjudicated pulmonary exacerbations, which showed clinically meaningful reductions with both doses compared with placebo. The annualised pulmonary exacerbation rate was 1.02 with 10 mg brensocatib and 1.04 with 25 mg brensocatib, compared with 1.29 for placebo. Both doses achieved statistical significance, with rate ratios of 0.79 (10 mg) and 0.81 (25 mg) vs placebo, representing around a 20% relative risk reduction.

The earlier WILLOW trial, involving 256 patients over 24 weeks, supported these findings, showing that brensocatib prolonged time to first exacerbation compared with placebo, with adjusted hazard ratios of 0.58 for the 10-mg dose and 0.62 for the 25-mg dose.

Dosing, Safety, and Monitoring

Brensocatib is administered as an oral tablet taken once daily, offering convenient dosing for patients. 

The most commonly reported adverse events include upper respiratory tract infections (nose and throat), gastrointestinal disturbances (diarrhoea and vomiting), headache, and dermatologic effects such as hyperkeratosis (small areas of skin thickening), rash, dermatitis (skin dryness and inflammation), and alopecia. Gum disorders were also reported.

Clinical trials showed a higher incidence of hyperkeratosis with brensocatib compared with placebo, though the overall incidence of adverse events remained similar across treatment groups. Prescribers should counsel patients about these potential side effects and monitor accordingly.

The MHRA will continue post-marketing surveillance of the medicine's safety and effectiveness. Complete prescribing information, including contraindications and drug interactions, will be available in the Summary of Product Characteristics and Patient Information Leaflet, to be published on the MHRA website within 7 days of approval. 

Healthcare professionals should report suspected adverse reactions through the Yellow Card scheme.