Brensocatib, marketed as Brinsupri, has gained FDA approval as a new treatment for bronchiectasis, according to a recent review by Dr. Albert Rizzo and Dr. James Chalmers. The approval, announced in August 2025, highlights both the drug’s efficacy and its reassuring safety profile, crucial for clinicians and patients alike.
In their discussion, Chalmers emphasized the positive outcomes from the phase 2 WILLOW trial and the extensive phase 3 ASPEN trial. Both studies indicated that adverse events associated with brensocatib occurred at rates comparable to those observed in placebo groups. Notably, despite the drug’s mechanism targeting neutrophil activity, there was no significant increase in pneumonia or other infection rates. This finding is particularly important given the essential role of neutrophils in the body’s defense against infections.
The most common side effect reported in the ASPEN trial was mild hyperkeratosis, which affected around 3% of patients receiving the higher dose. Chalmers noted that this skin thickening resembles manifestations seen in the rare Papillon-Lefevre syndrome, characterized by the absence of the DPP1 enzyme. However, he reassured that the instances observed in the trial were largely reversible and self-limiting, leading to only one patient discontinuing treatment. He advised clinicians to inform patients about this potential side effect, which may appear at various points during therapy, even after several months.
Understanding the Mechanism of Brensocatib
Brensocatib represents a novel approach in treating bronchiectasis, functioning as a first-in-class DPP1 inhibitor. By inhibiting DPP1 in the bone marrow, the drug effectively prevents the activation and packaging of proteolytic enzymes, such as neutrophil elastase and cathepsin G, into neutrophils. Consequently, while neutrophils still migrate to the lungs, their ability to cause tissue damage is diminished. This mechanism helps to reduce inflammation without broadly impairing the body’s infection defenses.
Chalmers highlighted that this targeted action is instrumental in explaining both the drug’s efficacy in minimizing exacerbations and its favorable safety profile. The innovative design of brensocatib may shift how bronchiectasis is treated, moving towards a more disease-modifying approach rather than just symptomatic relief.
Brensocatib’s approval marks a significant milestone in the management of bronchiectasis, as it is the first of its kind to receive FDA endorsement for this condition. As the landscape of bronchiectasis treatment evolves, the contributions of researchers and clinicians like Rizzo and Chalmers will be vital in guiding effective clinical practices.
As the medical community continues to assess the long-term effects and benefits of brensocatib, its introduction may redefine standards in bronchiectasis management, offering hope to many patients affected by this chronic respiratory condition.
