Brensocatib, marketed under the name Brinsupri, has garnered attention following its recent approval by the U.S. Food and Drug Administration (FDA) in August 2025. This approval marks a significant advancement in the treatment of bronchiectasis, a chronic condition characterized by the abnormal dilation of the bronchi. In a recent discussion, experts Albert Rizzo, MD, and James Chalmers, MBChB, PhD, provided insights into the drug’s safety and mechanism of action, highlighting its potential benefits for patients.
Both the phase 2 WILLOW trial and the extensive phase 3 ASPEN trial yielded promising results regarding the safety profile of brensocatib. According to Chalmers, the trials demonstrated that adverse events occurred at rates comparable to those observed with placebo treatments. Notably, despite the drug’s targeting of neutrophil activity, there was no increase in pneumonia or other infections, which is particularly important given the critical role neutrophils play in the body’s defense against pathogens.
While brensocatib poses some risks, the most significant side effect reported in the ASPEN trial was mild hyperkeratosis, affecting approximately 3% of patients receiving the higher dosage. Chalmers noted that this skin thickening bears similarities to findings in the rare Papillon-Lefevre syndrome, a condition characterized by the absence of the DPP1 enzyme. However, he emphasized that the cases observed in the trial were largely reversible and self-limiting, with only one patient discontinuing treatment due to this effect. Clinicians are advised to inform patients about this potential side effect, which can manifest at various points during therapy, even after several months of treatment.
Understanding the Mechanism Behind Brensocatib
Brensocatib operates through a novel mechanism as a first-in-class DPP1 inhibitor. By inhibiting DPP1 within the bone marrow, brensocatib prevents the activation and packaging of proteolytic enzymes, such as neutrophil elastase and cathepsin G, into neutrophils. This action allows neutrophils to reach the lungs while minimizing their capacity to inflict tissue damage, thereby reducing inflammation without broadly compromising the body’s ability to fend off infections.
Chalmers pointed out that this targeted approach aids in explaining both the drug’s efficacy in decreasing exacerbations and its favorable safety profile. The insights from the ASPEN trial underline the importance of brensocatib in shifting the treatment paradigm for bronchiectasis towards disease modification.
As healthcare professionals continue to explore innovative therapies for bronchiectasis, the inclusion of brensocatib may redefine patient management strategies. The positive safety data and unique mechanism of action position brensocatib as a promising option for clinicians seeking to improve patient outcomes and enhance quality of life.
In summary, the approval of brensocatib represents a key milestone in the treatment landscape for bronchiectasis. With ongoing research and clinical insights from experts like Rizzo and Chalmers, this new therapy may pave the way for more effective management of this challenging respiratory condition.
