EDS-PLU Studies for Treatment of Nasal Polyposis

Anju Peters, MD:Let's look now and dig deeper into a couple of those studies that have been done for EDS-FLU delivery. We'll talk about the 2 phase 3 studies, Navigate 1 and Navigate 2. Dareen, if you wouldn't mind introducing the study design and study endpoints, and then Drew can tell us the outcomes of the studies.

Dareen Siri, MD, FAAAAI, FACAAI: Wonderful. Thank you so much. With the EDS-FLU studies, the 2 pivotal phase 3 trials were called Navigate 1 and 2, and as you can see with the accompanying slide, they each had about 300 some patients and each of those duplicative arms. They were all both randomized placebo controls involving patients who had number 1, nasal polyps, and number 2, moderate to severe congestion obstruction. And it is important to know that these patients would be if I saw them in my clinic did nasal endoscopy etcetera, they would have been candidates for potentially surgery, these weren't patients who had mild nasal polyps or something like that. And there were a variety of patients enrolled, including patients who did not have a history of surgery but also patients who had had previous surgery. Patients were randomized into 1 of 3 arms, including EDS-FLU 93 micrograms, EDS-FLU 186 micrograms and then 372 micrograms or placebo and they had to do it twice daily for 24 weeks. There were 2 co-primary endpoints. One was the mean change in congestion obstruction which we know is the most significant symptom as Dr Peters had discussed earlier that is the most frustrating for patients. The thing that they complain about the most. And certainly, the next would be the mean change in the endoscopic total polyp grade and this in fact was graded at 0 to 3, so a total score of 6, 3 on each side. It is slightly different than some of the other clinical studies that you might read, so that's important to know. And then some important secondary outcome endpoints, such as the sinonasal outcome test 22 which we know is an objective measure of disease severity, quality of life and some of those even non-nasal symptoms that we talk. I'm going to turn it over to Drew who is going to tell you about the results.

Andrew White, MD:These are very similar study designs, and we have one outcome that is symptom based and then one outcome that is more objective looking at polyps score, and then the sinonasal outcome test or called the snot 22 score which is something that we pay careful attention to as something that correlates with our patient's quality of life. Looking at these results, I want to see how all these outcomes fair. And for Navigate 1, we see that there's a lot of improvement in both primary endpoints, statistical improvement. They met both of those primary endpoints, improvement in nasal congestion. And the endoscopic appearance also showed improvement in the size of the polyp. The polyp score improved and that also correlated not just this sense of nasal congestion but improvement in the total snot 22 score, which is a broader marker of quality of life. And the patients also reported that they felt- 80% of patients felt that they had significant improvement. I'll touch on the adverse effects or adverse events in a second. For Navigate 2, there's similar findings, again, these co-primary endpoints were both met. Improvement in congestion and polyp improvement, but there was also one other feature I want to call out. In some patients, there was a complete resolution of polyp, and in that study 25% of patients compared with only 8% in placebo. 25% with the EDS fluticasone had polyp elimination on at least one side. This speaks to a pretty significant effect all of these end points being met. Again, in this study improvement in this snot 22 score. And then another important part is as Dareen mentioned that these patients would have been eligible for surgery and depending on how much there's symptoms bothered them and their response to medical therapy may have in fact gone onto surgery. And in the patients that were treated with the EDS fluticasone, the patients that were eligible for surgery by the end of this study would have decreased by 62 to 67%. Big changes in what brought these patients into the study and how they ended up at the conclusion. And from a safety standpoint, there's no major differences between this device, the EDS fluticasone, and the typical nasal corticosteroid sprays that we've been using. So just some local irritation but nothing that goes beyond that.

Anju Peters, MD:Thank you both for sharing.

Transcript edited for clarity