Our Take
Brensocatib proved neutrophilic inflammation is druggable in bronchiectasis, but the drug does not replace airway clearance, antibiotics, or better patient stratification—it sits on top of them.
Why it matters
Bronchiectasis has been a symptom-management-only disease for decades. Brensocatib's 2025 approvals (US in August, EU in November) give the field its first regulatory and clinical reference point, forcing every pipeline program to prove it improves outcomes beyond reducing bacterial load or inflammation alone.
Do this week
Pulmonologists: review your bronchiectasis population for patients with two or more exacerbations in the prior year and discuss Brinsupri as an add-on to existing airway clearance and antibiotic regimens before next quarterly clinic planning.
Brensocatib Enters a Symptom-Heavy Field
Bronchiectasis treatment has relied on airway clearance, sputum-guided antibiotics, long-term macrolides, and inhaled antibiotics for chronic Pseudomonas aeruginosa infection. In 2025, Insmed's brensocatib (marketed as Brinsupri) became the first approved drug targeting a specific disease mechanism: neutrophilic inflammation that drives airway damage. The US FDA approved it in August; the European Union followed in November.
Brensocatib inhibits dipeptidyl peptidase 1 (cathepsin C), an enzyme that activates neutrophil serine proteases. These proteases are part of the immune response to infection but cause tissue injury when overactive. By dampening their activation, the drug reduces part of the inflammatory cycle that sustains the "vicious vortex" of impaired mucus clearance, infection, inflammation, and further airway damage.
The approval rested on ASPEN, a phase 3 trial of over 1,700 patients with non-cystic fibrosis bronchiectasis. Patients on brensocatib had fewer pulmonary exacerbations than placebo: 1.02 exacerbations per year (10 mg dose), 1.04 (25 mg dose), versus 1.29 for placebo (company-reported). Regulators applied different indications: the US approved it for patients aged 12 and older with non-cystic fibrosis bronchiectasis; the EU restricted it to those aged 12 and older with at least two exacerbations in the prior year.
A Reference Point, Not a Game-Ender
Brensocatib validates neutrophilic inflammation as a druggable target. It does not simplify bronchiectasis treatment. The disease still causes structural airway damage, chronic infection, impaired mucus clearance, and different inflammatory profiles across patient subgroups. Airway clearance, antibiotics, and macrolides remain central to care.
The approval also raises the bar for the pipeline. Earlier programs like ORBIT (liposomal ciprofloxacin for non-cystic fibrosis bronchiectasis) reduced bacterial burden but failed to improve respiratory symptoms or exacerbation risk consistently. One of two phase 3 studies met its primary endpoint; the other did not. That history means newer anti-infection approaches must prove clinical benefit, not just bacteriological effect.
The Pipeline Reflects Patient Stratification
Three therapeutic vectors are emerging. First, cathepsin C inhibitors: Boehringer Ingelheim's verducatib (BI 1291583) mirrors brensocatib's mechanism and is now in phase 3, evaluating exacerbation reduction, lung function decline, and respiratory symptoms.
Second, anti-infection approaches targeting chronic Pseudomonas. AstraZeneca's gremubamab is a bispecific monoclonal antibody hitting two bacterial structures (Psl and PcrV) to weaken biofilm formation and type 3 secretion. Phase 2 data showed reduced P. aeruginosa bacterial load. Armata Pharmaceuticals is testing AP-PA02, an inhaled bacteriophage, with phase 2 results in late 2024 showing reduced bacterial burden and favorable safety.
Third, selective biologics for inflammatory subgroups. Sanofi and Regeneron's itepekimab (anti-IL-33 monoclonal antibody) and AstraZeneca's benralizumab (targeting eosinophils, already approved in asthma) are in phase 2 and phase 3 respectively, betting that specific inflammatory phenotypes respond to cytokine-directed drugs.
The 2025 European Respiratory Society guideline still strongly recommends airway clearance, pulmonary rehabilitation, long-term macrolides for high-risk patients, and long-term inhaled antibiotics for chronic P. aeruginosa cases. Brensocatib sits atop this foundation, not beneath it. Future approvals will likely occupy similarly defined niches rather than becoming broad-use replacements for the current standard of care.