The When and How of Implementing New Anti-Neutrophil Therapies Into Standard Clinical Practice

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Dr. McShane: 
Welcome, everyone. I'm PJ McShane from the University of Texas Health Science Center in Tyler, Texas. I'm here with my colleagues, Dr. Greg Tino and Dr. Ashwin Basavaraj. We are talking about neutrophil elastase inhibition therapy in patients with non-cystic fibrosis bronchiectasis.

So this is a new era. And we think that based on early phase 2 trials that there is a role for neutrophil elastase inhibition in bronchiectasis patients. So I'm going to ask Dr. Tino first, what would be the clinical benefit for initiating this therapy in your patients who have bronchiectasis?

Dr. Tino: 
Thanks, PJ. So as you two know and as any of our colleagues who take care of bronchiectasis patients know one of the most challenging aspects of their care is treating frequent exacerbations, which we know has adverse impact in the long term. Frequent exacerbations beget more exacerbations, adversely impact quality of life. So having a medication and anti-neutrophil medication, for example, that reduces the exacerbation would have really just a wonderful salutary effect on our patients. And we do have some data of a human neutrophil elastase medication that was studied in a phase 2 clinical trial called the WILLOW trial that actually showed that it positively impacted and reduces the rate of exacerbation and the total number of exacerbations in patients who were treated with the drug.

Dr. McShane: 
Dr. Basavaraj, we want to hear what you think.

Dr. Basavaraj: 
Yeah, I mean, I agree with everything Greg said. I think, you know, some of the benefits of anti-neutrophil therapies are improving quality of life of patients, reducing symptoms, as we mentioned, reducing exacerbations. But with that comes a potential reduction in antibiotic use, right? A lot of these patients with exacerbations get frequent antibiotics and, you know, with resistance that can develop with that. So with the use of anti-neutrophil therapies, can we reduce that? And steroids also are often used in patients with exacerbations, which comes along with side effects for prolonged use. So, you know, with the use of anti-neutrophil therapies, can we also reduce the side effects with prolonged steroid use?

As Greg mentioned, there has been phase 2 data that has, you know, shown benefit and, you know, recently there was a phase 3 study on anti-neutrophil therapies that closed out. So we're excited to see, you know, the results of that and see if there's potentially a new medication in the pipeline to really target inflammation.

Dr. McShane: 
One of the things that I think of when we may soon have a drug that is indicated for patients with frequent exacerbations is that we have to make sure these patients really know what bronchiectasis exacerbations are. So they're really reporting them and so that we can capture the patients who are going to be right for this drug. So I hope that you know that as we sort of educate our colleagues throughout the country that people will be putting some time into teaching their patients what the exacerbation is, so we can capture everyone who is going to be right for this drug.

Dr. Tino: 
PJ, with all the - with - when there are new therapies, there's always a concern about potential downsides. Do you have any particular potential concerns related to the use of anti-neutrophil therapy?

Dr. McShane: 
Well, initially, from the animal trials, I think there was a concern about skin adverse events and gum, gingivitis type gum disease, I think that has not ended up to be as big of a concern as we feared it would have been from the phase 2 trial data. But it certainly is an important aspect that we need to follow these patients. And then again, as was mentioned earlier, this phase 3 trial, the ASPEN trial, will provide more information about the potential adverse effects that we need to look out for.

Dr. Tino: 
Yeah, I agree. It's a large trial, multinational trial, so I think we're going to mine lots of good data, but not only potential efficacy, but also potential downsides. You know, as I think about anti-neutrophil therapy in general, anti-inflammatory therapy, you know, the question that comes up is, could we impact the natural history of bronchiectasis, right? By reducing inflammation at its core, do we have an ability to change the natural history and prevent progression and prevent the progression of symptoms, prevent radiographic disease, etc, etc.? What do you folks think?

Dr. Basavaraj: 
Yeah, I think, you know, as we - now we talk about the vicious cycle and the vicious vortex in bronchiectasis and this might be a new, you know, medication that we can use to try to break the vortex, right? So can we prevent this, you know, repeated inflammation in bronchiectasis and further damage with the use of anti-neutrophil therapy. I think it's very exciting to see if that will, you know, prevent this perpetuation of, you know, inflammation and infection that, you know, these patients often face.

Dr. Tino: 
And that obviously will take quite a while to sort out but I think that would be a very important area to look at from an academic perspective as well.

Dr. McShane:  
Thank you both. That was a great discussion. So Ashwin, do you want to summarize?

Dr. Basavaraj: 
Sure, PJ. So we spoke about anti-inflammatory therapies, potential ones for bronchiectasis that are being actively studied. You know, these therapies have the potential to reduce symptoms, reduce bronchiectasis exacerbations, and improve quality of life for our patients. Obviously, with any new therapies, there are always side effects to be aware about. So we have to see what these clinical trials show and potentially, you know, could these be used in our patients with bronchiectasis? I think we have to wait and see.

Dr. McShane: 
Well, thank you so much, everyone.

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