Brensocatib Dosing for Bronchiectasis
Based on the most recent clinical evidence, brensocatib at doses of 10 mg or 25 mg once daily is recommended for the treatment of bronchiectasis, with both doses showing efficacy in prolonging time to first exacerbation.
Dosing Recommendations
The Phase II WILLOW trial provides the strongest evidence for brensocatib dosing in bronchiectasis:
- Standard dosing options:
- 10 mg once daily
- 25 mg once daily
Both doses demonstrated efficacy in the WILLOW trial, with the following outcomes 1:
- Prolonged time to first exacerbation compared to placebo
- Reduced exacerbation rates
- Decreased sputum neutrophil elastase activity
Pharmacokinetic Considerations
- Administration: Can be taken with or without food 2
- Absorption: Food slightly delays absorption (by 0.7-1.7 hours) but does not significantly affect overall exposure 2
- Half-life: 22-28 hours, allowing for once-daily dosing 2
- Accumulation: Approximately 2-fold accumulation at steady state 2
Dose Selection Factors
When selecting between 10 mg and 25 mg doses, consider:
Efficacy profile:
Patient subgroups: Both doses showed benefit across various patient subgroups 3:
- Regardless of disease severity (BSI score)
- With or without P. aeruginosa infection
- Regardless of prior exacerbation frequency
- With or without concurrent macrolide use
Special populations:
Safety Considerations
Monitor for potential adverse events:
- Dental effects: Regular dental/periodontal care recommended, though 24-week treatment showed no significant periodontal disease progression 5
- Skin effects: Skin exfoliation reported as a common adverse event 2
- Other common adverse events: Headache 2
Integration with Current Bronchiectasis Management
Brensocatib represents a novel approach targeting neutrophil-mediated inflammation through DPP1 inhibition, which is distinct from current bronchiectasis treatments that focus on:
- Airway clearance techniques 6, 7
- Mucoactive agents 6
- Long-term antibiotics (particularly macrolides) 6
Monitoring Recommendations
- Assess clinical response through exacerbation frequency and symptoms
- Regular dental examinations to monitor for potential periodontal effects
- Monitor for skin manifestations
- Standard bronchiectasis monitoring as recommended by guidelines, including spirometry every 3-6 months 7
Brensocatib's mechanism as a DPP1 inhibitor represents a novel approach to bronchiectasis management by targeting neutrophil serine proteases that contribute to inflammation and tissue damage, rather than focusing solely on infection control like traditional therapies.