So far, the visible strategy around bronchiectasis has been managing the problems it creates — mucus retention, repeated infections, airway inflammation, and exacerbations. Airway clearance, sputum-guided antibiotics, long-term macrolides in selected patients, and inhaled antibiotics for patients with chronic Pseudomonas aeruginosa infection remain central parts of care.
In 2025, that treatment landscape changed with the approval of brensocatib, marketed by Insmed as Brinsupri. The drug became the first approved treatment specifically for non-cystic fibrosis bronchiectasis, first in the United States in August and then in the European Union in November. Its approval also gave the field a clinical and regulatory reference point after several bronchiectasis programs had struggled to translate reductions in bacterial load or inflammation into clear benefits for patients.
Brensocatib does not make bronchiectasis a simpler disease to treat. The condition still causes structural airway damage, chronic infection, impaired mucus clearance, and different inflammatory profiles.
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Why bronchiectasis is difficult to treat
Patients with bronchiectasis often experience persistent cough, excess mucus production, recurrent chest infections, and periodic exacerbations that can lead to additional lung damage. The condition develops when the airways become permanently widened, making it harder to clear mucus and creating an environment where bacteria can persist.
The disease is often described using the concept of a “vicious vortex.” Impaired mucus clearance promotes infection, infection sustains inflammation, and inflammation damages the airways further. The damaged airways then become even less effective at clearing mucus, allowing the cycle to continue.
This multiplicity of symptoms is reflected in treatment options. Airway clearance techniques remain a cornerstone of care, while antibiotics are used to treat exacerbations and suppress chronic infections in selected patients. Long-term macrolides and inhaled antibiotics can reduce exacerbation risk for some patients, particularly those with chronic Pseudomonas aeruginosa infection.
This observation is also true in the pipeline. Some developers are trying to reduce the neutrophilic inflammation that drives airway damage. Others are targeting chronic bacterial infection directly. Several programs are exploring whether biologics used in other respiratory diseases could benefit specific bronchiectasis subgroups. The result is a pipeline that features multiple mechanisms, multiple patient populations, and no single explanation for why bronchiectasis progresses.
Brensocatib, the first approved targeted treatment for bronchiectasis
Brensocatib changed the landscape as it is not an antibiotic and does not target mucus clearance directly. Its route into bronchiectasis is neutrophilic inflammation, one of the major processes involved in airway damage.
The drug inhibits dipeptidyl peptidase 1, also known as cathepsin C, an enzyme involved in activating neutrophil serine proteases. They are part of the neutrophil response to infection, but excessive activity has been linked to airway inflammation and tissue injury in bronchiectasis. By reducing their activation, brensocatib dampens part of the inflammatory process.
The approval was based on ASPEN, a phase 3 trial that randomized over 1,700 patients with non-cystic fibrosis bronchiectasis. Patients receiving once-daily brensocatib had fewer pulmonary exacerbations than those receiving placebo, with annualized rates of 1.02 for the 10 mg dose, 1.04 for the 25 mg dose, and 1.29 for placebo.
Regulators did not frame the drug identically on both sides of the Atlantic. In the United States, Brinsupri is indicated for non-cystic fibrosis bronchiectasis in patients aged 12 and older. In the European Union, the approval is for patients aged 12 and older who have had at least two exacerbations in the previous year, placing it slightly later in the pathway.
The approval gives bronchiectasis its first targeted treatment, but the mechanism also shows the limits of a single approach. Brensocatib validated neutrophilic inflammation as a druggable part of the disease. It does not remove the need for airway clearance, antibiotics, or better identification of patients whose disease is driven mainly by chronic infection or other inflammatory pathways.
The bronchiectasis pipeline: three therapeutic bets
The bronchiectasis pipeline now has a reference point in brensocatib, but it is not simply filling up with lookalike drugs. The main candidates in development reflect different aspects of the disease.
The most direct continuation of the brensocatib story is Boehringer Ingelheim’s verducatib, also known as BI 1291583. Like brensocatib, verducatib inhibits cathepsin C, or DPP1, to reduce neutrophil serine protease activity in the airways. In phase 2, treatment with BI 1291583 reduced the risk of experiencing an exacerbation in adults with bronchiectasis. Boehringer has since moved the drug into phase 3, evaluating primarily whether verducatib can reduce pulmonary exacerbations and also looking at lung function decline and respiratory symptoms.
A second part of the pipeline focuses more directly on chronic infection. The key example is AstraZeneca’s gremubamab, a bispecific monoclonal antibody for patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The drug targets two bacterial structures: Psl, an exopolysaccharide involved in biofilm formation, and PcrV, a component of the type 3 secretion system. The idea is to weaken Pseudomonas instead of suppressing the inflammatory response.
P. aeruginosa infection is one of the more clinically recognizable bronchiectasis phenotypes. It is associated with poorer outcomes, and it gives drug developers a more defined patient population. In phase 2, gremubamab reduced P. aeruginosa bacterial load compared with placebo, with similar rates of adverse events and serious adverse events between the treatment and placebo groups.
Armata Pharmaceuticals has a different take on chronic infection with AP-PA02. It is an inhaled bacteriophage candidate being tested in patients with non-cystic fibrosis bronchiectasis and chronic pulmonary P. aeruginosa infection. The company reported phase 2 data in late 2024, showing reductions in bacterial burden and a favorable safety profile. This is still less validated than the larger pharma programs, but it is a differentiated approach to managing airway infection.
The third bet is a more selective one: biologics for inflammatory subgroups. Sanofi and Regeneron’s itepekimab, an anti-IL-33 monoclonal antibody, is currently being tested in a phase 2 study in non-cystic fibrosis bronchiectasis.
AstraZeneca’s benralizumab is another example, but its phase 3 study is also focusing on patients with eosinophilic inflammation, in addition to non-cystic fibrosis bronchiectasis. Eosinophils are immune cells involved in certain inflammatory responses and play a role in eosinophilic asthma. Benralizumab depletes these cells and is already approved in asthma, making it a logical candidate to test in bronchiectasis patients who show a similar inflammatory profile.
Where does the field go from here?
Brensocatib’s approval does not replace the current foundations of bronchiectasis care. The 2025 ERS guideline still strongly recommends airway clearance techniques for most patients, pulmonary rehabilitation for those with impaired exercise capacity, long-term macrolides for patients at high risk of exacerbations, and long-term inhaled antibiotics for patients with chronic Pseudomonas aeruginosa infection who remain at high risk despite standard care.
However, now, a new bronchiectasis treatment does not enter an empty field, and it has to improve outcomes on top of practical disease management. For CatC inhibitors, that means showing that reducing neutrophil serine protease activity can consistently lower exacerbation risk and, ideally, affect symptoms or lung function.
For the infection-focused side of the field, bronchiectasis trials have shown that reducing bacterial burden is not always enough. One of the largest examples was the phase 3 ORBIT program evaluating liposomal ciprofloxacin, an inhaled antibiotic developed by Aradigm and later Grifols, in patients with non-cystic fibrosis bronchiectasis. While one of the two phase 3 studies met its primary endpoint, the other did not, preventing the program from delivering the evidence needed. Subsequent analyses also found no significant improvement in respiratory symptoms over 48 weeks.
That history makes newer anti-Pseudomonas approaches interesting, but it also sets a higher bar for success. Gremubamab reducing P. aeruginosa bacterial load is encouraging, but the clinical question is ultimately about symptoms, whether that translates into fewer exacerbations or slower disease progression.
The current pipeline already reflects a more selective approach than the previous broad bronchiectasis development. This is probably where the field is heading: not away from what already works, but toward drugs that sit on top of them for more clearly defined patients.
