Brensocatib Approval Highlights Potential of DPP1 Inhibitors for Neutrophil-Mediated Diseases: James D. Chalmers, MBChB, PhD

Part 3 of The American Journal of Managed Care^®'s conversation with James D. Chalmers, MBChB, PhD, professor of respiratory medicine at the University of Dundee in Scotland, explores the significance of brensocatib (Brinsupri; Insmed) as the first dipeptidyl peptidase 1 (DPP1) inhibitor approved for a neutrophil-mediated disease, specifically non–cystic fibrosis bronchiectasis.

Watch parts 1 and 2 to learn more about what brensocatib adds to the treatment landscape for this patient population, as well as its safety and tolerability profile.

This transcript has been lightly edited; captions are auto-generated.

Transcript

Brensocatib is the first DPP1 inhibitor approved for a neutrophil-mediated disease. How significant is this breakthrough for bronchiectasis, and what potential does it have in other neutrophil-driven diseases, such as chronic obstructive pulmonary disease (COPD) or severe asthma?

This is a real landmark, both from a clinical point of view, as somebody who looks after people with bronchiectasis, but also [because] I did my PhD in neutrophil biology. I've been working on neutrophil therapeutics for most of my career, and this is the first time we've been able to target neutrophilic inflammation successfully and show that it has clinical benefits.

It has a number of implications. In the past, I've been told that neutrophils are undruggable because they're so important to your immune response that if you impair neutrophils or affect them in some way, you'll increase the risk of infection. Brensocatib shows that that's not true. You can target neutrophils if you do it in this very precise way that DPP1 inhibitors do, and it will not increase the risk of infection.

That opens up the field of neutrophil targeting for other neutrophil-driven diseases, and you already mentioned 2 of them that are neutrophil-driven; COPD and T2-low asthma are both neutrophil-driven. I would think this sort of approach would have the potential for benefit in those diseases, as well. Cystic fibrosis, similarly, is neutrophil-driven.

Outside of the lung, there are many, many diseases that are neutrophil-driven or have an important neutrophil component. This approval and the evidence that we've generated with brensocatib could also have implications beyond the lung, and that's quite exciting.

I think this is a step forward, not just for bronchiectasis, but also for our understanding and our ability to treat neutrophil-mediated diseases in general.