I'm James Chalmers and I'm the Professor of Respiratory Medicine at the University of Dundee in the UK. And I was the host and chair of this year's World Bronchiectasis Conference that was held at the University of Dundee, here in my hometown.
There were three key aspects, I think, to this year's World Bronchiectasis Conference, One was late breaking, exciting clinical trial data. And we worked very hard with partners to bring new data to the conference.
The other key thing that we tried to bring out in the conference is the role of early career researchers. Bronchiectasis has been a neglected field. We don't have that many scientists and clinicians who do research into bronchiectasis. So, it's a very small community. And the only way that we grow that community is to bring through, what one of the participants in the conference, Lucy Morgan, called on bright young things.
The third thing that was really important and we tried to make a focus of the conference was the multidisciplinary team. Patients with bronchiectasis aren't just looked after by doctors. They’re looked after by physiotherapists, by specialist nurses, by a number of other professionals within the team and so this year we made a big effort to partner with societies representing those multidisciplinary teams.
The World Bronchiectasis Conference was the first detailed presentation of the results of the Aspen trial, which is a phase three trial of an anti-inflammatory treatment called Brensocatib in people with bronchiectasis. And this is a real watershed moment for people with bronchiectasis and also, those of us who look after these patients.
This was by far the largest clinical trial program ever conducted in bronchiectasis. We randomized 1680 patients with bronchiectasis to one of two doses of a Brensocatib or placebo over a period of 12 months. And the primary outcome of the trial was the frequency of exacerbations.
The hypothesis behind the trial is that if you reduce lung inflammation caused by these cells called neutrophils you would reduce exacerbations.
And to our delight, what we were able to present at the conference was that both doses of Brensocatib reduced the frequency of exacerbations by approximately 20%. That's clinically significant and it was highly statistically significant. So. the trial met its primary endpoint.
That's a huge moment that generated a lot of excitement from the attendees because we've struggled to get positive trials in bronchiectasis in the past. But the story doesn't finish there because we also saw consistency of efficacy across the, the exacerbation endpoints.
The time to the first exacerbation was prolonged. There was a 40% increase in the odds of patients going a year without an exacerbation. Now that to a patient is really impactful. This is a treatment that's going to greatly increase the chances that you can have the next year without experiencing exacerbation.
But we weren't finished there because we also had very exciting results from the secondary endpoints. If you ask a patient with bronchiectasis ‘What do you want for a treatment?’ Sure, they will say I want a reduction in exacerbations. They also want a treatment that's going to prevent them from getting worse because bronchiectasis is a progressive disease.
And so, we were really excited to present the data on lung function that showed that the 25mg dose of Brensocatib really, profoundly stabilized lung function. So, the difference at the end of the trial was 38mL between the two arms. That may not sound like a lot, but you and I, if we've not got bronchiectasis, will decline by about 30 mL per year. People with bronchiectasis decline by about at 60 to 70 mL per year. So, the difference between having bronchiectasis and being healthy is about that magnitude of benefit that we saw in Aspen. So, it's essentially taking away that excess lung function decline that we see when you have bronchiectasis. It's the first time we've ever seen a treatment, to my knowledge, that we can say to a patient, this can stop you from declining as rapidly as you otherwise would.
We also presented some novel data showing an improvement in symptoms with the 25mg dose.
So, if I summarize all of that, the Aspen trial showed for the first time an anti-inflammatory treatment can prevent exacerbations, prolong the time to first exacerbation, slow down the rate and decline in lung function at the 25mg dose, and also improve patients’ symptoms on a daily basis with the 25mg dose.
This is a major breakthrough in the field of bronchiectasis. And it is the treatment is going to make a big impact for our patients.
The Airleaf trial was a phase two study of a similar compound, which is again a novel cathepsin C (CatC) inhibitor in patients with bronchiectasis.
It was a phase two trial. So, it's smaller than the Aspen trial. And in this study, it was a dose finding study. So, the medication is called by 1291583 because it doesn't yet have a, an official drug name.
So, three doses of that drug were tested five milligrams, 2.5 milligrams, and one milligram against placebo. All of the patients did a minimum of six months. But the patients who were enrolled early on could be followed up for up to a year. So, we were given the top line data. Remember it was a dose finding study, so the goal of the study was to show that as the dose is increased, you see greater benefit on the endpoint, which is time to first exacerbation.
And the data that we were able to show was exactly that, that as the dose is increased, you see a positive dose response curve with a p value of 0.045. So, it met the statistical significance required to say we've got a positive study. We also were able to show some safety data, to say that we didn't see any major safety concerns. There was no increase in infections, which is also always something that you think about when considering an anti-inflammatory medication. But we saw a little bit of skin thickening, hyperkeratosis, which is something that is seen with this class of medication as you increase the dose.
I think we're on the cusp of a revolution in bronchiectasis, and I don't say that lightly. I said at the end of the talk that I gave with Airleaf that for the first six World Bronchiectasis Conferences I felt like we turned up to a conference and we talked about failed trials and the fact that we needed to find therapies that worked. And suddenly we came to the seventh World Bronchiectasis Conference, and we were talking about positive trials and multiple positive trials. The response from the patient community, and there were a lot of patients there in the room, was overwhelming. Joy, happiness, you know, encouragement, hope for the future because we're starting to see new therapies come through that can really help them.
What I'm expecting to see in the next year is firstly Brensocatib will come to the market, and it will go from being something in research to being something that is used by patients. I really hope that we see that happening as soon as possible because there are a lot of patients that really need those treatments.
But I think demonstrating that we can deliver positive trials, patients with bronchiectasis are an enthusiastic group who are willing to participate in research, is going to encourage a lot of other companies who've got potential molecules to come into the space. And so, I'm expecting to see a large growth in the number of clinical trials. I'm expecting to see more positive clinical trials. And that's wonderful because that's going to translate to better treatment for my patients, better outcomes for my patients and a lot of hope.
