When we look at the um design of the willow and then the Aspen trial um to evaluate Brent Brentocaib as a um a neutrophil elastase inhibitor, it really was based on a, a lot of work that's been done over the years to kind of identify the, the main targets uh for this new class of drugs. And I think, uh, you know, over the past 10 to 15 years, there's been, we've come to the realization that um exacerbations are bad for patients with bronchiectasis, and the more frequent the patient, more frequently the patient exacerbates, the worse their long-term prognosis is, the more likely they'll have a high symptom burden. The more likely they'll need to be hospitalized and have advanced therapies. So I, I would say that was the number one reason, um, the, or all those reasons why, uh, the reduction in exacerbations was decided as the primary endpoint in, in these trials, um, because it is a clinically relevant. Uh, it's relevant to the patient, it's relevant, uh, to the prognosis of the patient, and it's, it also has implications for the utilization of healthcare. So that's where we hit on the uh primary endpoint being reduction in exacerbations. And then, you know, a number of secondary endpoints were uh discussed uh for these trials, and, and of course, all of this has been informed by prior trials and bronchiectasis. Uh, you know, you do know that most of the prior trials were looking at inhaled antibiotics that did not meet their primary endpoint either in reduction of exacerbations or in, in quality of life. But we've learned a lot from those trials in order to design these um uh for forensic captive trials. So, uh, having, you know, clinically relevant, um, secondary endpoints is very important, uh, to the patient, right? And, and to us and, and to the, um, the, the, uh, outcome of the patient. So, um, that we use the validated quality of life questionnaire, uh, that have been developed through previous trial work, uh, obviously was very important and to see improvement. A clinically relevant improvement in that marker is very encouraging in the uh aspen trial. And also, um, you know, typically we think that FEV1 does not change that much in patients with non-cystic fibrosis, bronchiectasis, even with exacerbations. So having a secondary endpoint to look at um FEV1 change was obviously important because we all measure that in our patients, but that the 25 mg dose in the Willow trial, um, sorry, in the Aspen trial actually showed a diminution in the normal reduction of FEV1 was very encouraging. So, you know, bottom line is all these trials are designed, um, obviously to hit the, the clinically relevant endpoints and Um, you know, this is all pre-designed and, and based on, um, prior trials that have been done.
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