Mark L. Metersky, MD, FCCP, FACP, professor of medicine and director of the Center for Bronchiectasis Care at UConn Health, has prescribed brensocatib since its approval and shared his approach to patient selection and tolerability in an interview with HCPLive.
"Bronchiectasis is quite heterogeneous, so it's likely not every patient will benefit," Metersky said. "For me, what I'm doing is using it in patients who have frequent exacerbations."
Brensocatib Patient Selection and ASPEN Trial Data
The ASPEN trial randomized patients with non-cystic fibrosis bronchiectasis to 10 mg brensocatib, 25 mg brensocatib, or placebo for 52 weeks across international sites. Both doses met the primary endpoint of a reduced annualized exacerbation rate compared with placebo, and the 25 mg dose additionally slowed the rate of forced expiratory volume in 1 second (FEV1) decline.¹
Metersky said patients with a high daily symptom burden, such as frequent cough with copious purulent sputum despite an absence of frequent exacerbations, may also derive benefit based on the drug's mechanism of action and the pattern of trial results. He added patients with rapidly declining lung function are additional potential candidates, given the 25 mg dose's demonstrated effect on FEV1 decline, though data specific to this subgroup remain unavailable.
Brensocatib Safety Profile and Patient Tolerability
Frequently Asked Questions
What is brensocatib approved for?
Brensocatib (Brinsupri) is approved by the FDA as a disease-modifying therapy for non-cystic fibrosis bronchiectasis in patients 12 years and older, based on results from the phase 3 ASPEN trial.
How does brensocatib work?
Brensocatib is an oral, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), an enzyme responsible for activating neutrophil serine proteases implicated in bronchiectasis airway inflammation.
Which bronchiectasis patients are most likely to benefit from brensocatib?
Metersky prioritizes patients with frequent exacerbations, the population studied in ASPEN, and considers patients with a high daily symptom burden or rapidly declining lung function additional potential candidates, though these groups were not directly studied in the trial.
The most common adverse events in ASPEN were consistent with the safety profile observed in earlier studies, and the phase 3 trial did not show a significant signal for increased periodontal disease risk with brensocatib.¹ Metersky said the drug's distinctive tolerability profile, including hyperkeratosis and periodontal changes, has not deterred patients from starting or continuing therapy in his practice.
He recalled one patient who asked if her teeth would fall out before starting treatment.
"That's not been an issue patients fear," said Metersky. "In truth, we didn't really see a significant signal for increased risk of periodontal disease in the phase 3 study."
He advises patients to brush twice daily, floss, and see their dentist regularly, noting any periodontal changes would likely develop slowly and be caught early. Metersky said he has also observed skin thickening and sloughing, most often behind the knees, elbows, feet, and hands, in one patient, but described the finding as uncommon in his experience.
The 1-year mark followed the American College of Chest Physicians' first North American clinical practice guideline for adult bronchiectasis, published in 2026, which includes long-term brensocatib among 13 conditional recommendations for patients with frequent exacerbations.³ Even with an approved therapy and dedicated guideline, unmet needs such as chronic cough, sputum burden, and disease progression persist across the bronchiectasis population.⁴
Watch the accompanying dynamic feature here: One Year Later: How Brensocatib Has Changed Bronchiectasis Care
Metersky’s disclosure includes Insmed.
References
Chalmers JD, et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. Published online April 23, 2025. doi:10.1056/NEJMoa2411664
