Brensocatib Brings DPP1 Inhibition to the Bronchiectasis Field

In this HCPLive RX Review Special Report, Albert Rizzo, MD, and James Chalmers, MBChB, PhD, turn their attention to brensocatib, the first FDA-approved therapy for non–cystic fibrosis bronchiectasis as of August 2025, marketed as Brinsupri. Brensocatib, a selective and reversible inhibitor of dipeptidyl peptidase 1, targets neutrophil-driven inflammation, an underlying driver of disease progression. Chalmers reviews findings from the phase 3 ASPEN trial, which enrolled over 1,700 patients and demonstrated a 20% reduction in exacerbations across both tested doses, with the higher dose also slowing lung function decline and showing nominal improvements in symptoms.

Chalmers emphasizes that trial participants had symptomatic disease and frequent exacerbations, underscoring the significant burden bronchiectasis imposes even in individuals with relatively preserved lung function. He notes that earlier intervention with anti-inflammatory therapy is likely advantageous, helping prevent progression to severe disease. By addressing exacerbation frequency and lung function decline, brensocatib offers a new pathway for modifying disease trajectory rather than relying solely on supportive care.

The discussion also highlights where brensocatib fits within current standards of care. Rizzo points out that airway clearance and antibiotic strategies remain essential, while Chalmers clarifies that brensocatib was evaluated as an add-on to existing therapies, including long-term macrolide use. He envisions the agent as either complementary to or, in some cases, an alternative for patients unable to tolerate macrolides, given their limitations and contraindications. Together, they underscore that brensocatib is not a replacement but rather a critical new tool for clinicians seeking to reduce exacerbations, preserve lung function, and expand therapeutic options in bronchiectasis.

Our Panelists:

Albert Rizzo, MD, is a pulmonologist at ChristianaCare Pulmonary Associates at the ChristianaCare in Newark, Delaware, and clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia. Triple board certified in internal medicine, pulmonary, critical care and sleep medicine, he also served as the former Chief Medical Officer of the American Lung Association.

James Chalmers, MBChB, PhD, is a Clinical Professor (Teaching and Research) of Respiratory Research, Respiratory Medicine and Gastroenterology, at University of Dundee, United Kingdom, where he also serves as Asthma and Lung UK Chair of Respiratory Research. He was a primary investigator on Insmed's ASPEN trial of brensocatib.

Editor's note: Rizzo's disclosures include Pfizer, AstraZeneca, and Genentech. Chalmer's disclosures include AstraZeneca, Boehringer Ingelheim, Genentech, Gilead, Grifols Biologicals, Insmed, Novartis, and Zambon.

Reference

Johnson V. FDA Approves First Bronchiectasis Therapy, Brensocatib, for Ages 12 and Up. HCPLive. Article. August 12, 2025. https://www.hcplive.com/view/fda-approves-first-bronchiectasis-therapy-brensocatib-12-up