In part 2 of an interview with James D. Chalmers, MBChB, PhD, professor of respiratory medicine at the University of Dundee in Scotland, he expands upon the safety and tolerability profile of brensocatib (Brinsupri; Insmed), which received FDA approval last week for the treatment of patients with non–cystic fibrosis bronchiectasis.
Watch part 1 to hear his insights on the ASPEN trial (NCT04594369) that supported this approval and how the therapy may change the treatment landscape for this patient population.
This transcript has been lightly edited for clarity; captions are auto-generated.
Transcript
What should clinicians know about the safety and tolerability profile of brensocatib? How do you expect it to be managed in practice?
The safety was very reassuring. The incidence of adverse events—which is always what we look for in clinical trials—and serious adverse events were very similar between the placebo group and the 2 treatment groups, so there was no evidence that there was any significant safety issue.
We particularly look for the frequency of infections because, I think, clinicians, when they hear that you’ve got an anti-inflammatory drug, they think, “Oh, is that going to increase the risk of infection?” The really reassuring thing to let everyone know is that there was no increased risk of pneumonia or other types of infections, which is remarkable for a treatment that targets the neutrophil as an anti-inflammatory approach. That’s also really reassuring.
There is this rare genetic condition called Papillon-Lefèvre syndrome, which is incredibly rare, and it’s caused by a knockout in this gene called dipeptidyl peptidase 1, which is the mechanism of action of the drug. We look very carefully for dental adverse effects and skin adverse effects, because those are the manifestations of that disease.
We don’t see any dental issues in the trial, and there were no clinically significant issues either in the phase 2 trial from a dental point of view. The only thing that really showed up in the phase 3 trial was this slightly higher frequency of hyperkeratosis. Just to put that in some context for your viewers, there were 4 cases in the placebo group, 8 cases in the 10 mg group, and 16 cases in the 25 mg group.
When you consider that there are more than 500 patients in each of those arms, these are quite rare [adverse] effects. Importantly, they were mild and manageable. There was actually only 1 patient in the whole trial who discontinued because of their hyperkeratosis as an adverse effect.
In practice, I don’t think we’re going to have any significant issues with this. Some patients will develop a bit of hyperkeratosis that seems to respond in the trial to a treatment interruption; it just goes away. That’s how I would expect to manage it in clinical practice.
