The recent FDA approval of brensocatib, marketed as Brinsupri, marks a significant advancement in the treatment of bronchiectasis. This medication, which received approval in August 2025, is the focus of discussions led by experts Albert Rizzo, MD, and James Chalmers, MBChB, PhD, regarding its safety profile and unique mechanism of action.
Both the phase 2 WILLOW trial and the extensive phase 3 ASPEN trial demonstrated that brensocatib has a reassuring safety profile. According to Chalmers, adverse events and serious complications occurred at rates comparable to those seen with placebo treatments. Notably, despite the drug’s aim to modulate neutrophil activity, there was no increase in pneumonia or other infections—a crucial finding considering the protective role of neutrophils in the immune response.
Chalmers highlighted a notable side effect observed during the ASPEN trial: mild hyperkeratosis, which affected approximately 3% of patients receiving the higher dosage. This skin thickening is reminiscent of symptoms seen in the rare Papillon-Lefevre syndrome, where the DPP1 enzyme is absent. However, Chalmers reassured that in the trial, these cases were largely reversible and self-limiting, only resulting in one discontinuation due to the side effect. He advised clinicians to inform patients about this potential effect, which may manifest at various points during treatment, even after several months.
Chalmers also elaborated on brensocatib’s innovative mechanism of action as a first-in-class DPP1 inhibitor. By inhibiting DPP1 in the bone marrow, brensocatib prevents the activation and packaging of proteolytic enzymes such as neutrophil elastase and cathepsin G within neutrophils. Consequently, while neutrophils still migrate to the lungs, their capacity to cause tissue injury is diminished. This targeted approach not only reduces inflammation but also preserves the body’s ability to defend against infections, which Chalmers notes is key to explaining both the drug’s efficacy in reducing exacerbations and its favorable safety profile.
The ongoing dialogue surrounding brensocatib underscores its potential to shift the paradigm in bronchiectasis treatment toward disease modification. This represents a crucial advancement for patients suffering from this chronic condition, which often leads to severe respiratory complications.
The insights provided by Rizzo and Chalmers highlight the importance of understanding both the safety and functionality of new treatments in the context of existing therapeutic landscapes. As clinical research continues to evolve, the role of innovative therapies like brensocatib will be closely monitored, paving the way for improved patient outcomes in bronchiectasis management.