Episode Transcript
Industry Insights: Surmount OSA Trial Transcript
0:00
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0:22
WEBER: Welcome to the Obesity Medicine Association's podcast, Obesity a Disease. My name is Doctor Christopher Weber. I serve on the board of trustees for the Obesity Medicine Association, and I am the medical director for Ascension Wisconsin's bariatric services. So this is a new industry insight series, and we'll be interviewing industry experts on timely and important topics in obesity medicine.
Today we're joined by Doctor Kevin Trice. Dr. Trice, thank you so much for joining us. He's the executive director of Global Medical Affairs, Cardio Metabolic Health at Lilly, and we're going to discuss the SURMOUNT OSA trial and its implications for clinical practice. Doctor Trice, welcome and thank you for being here.
1:04
TRICE: Thank you, Doctor Weber. I'm, I'm excited to be here and of course excited to share with you and your members, of course, some of the data behind our kind of pivotal clinical trials from SURMOUNT OSA and some of the other, you know, recent trial developments in the area of obesity medicine, particularly in patients with moderate to severe obstructive sleep apnea.
1:23
WEBER: Yeah, perfect. I know we're hearing all sorts of interest for this. So, this, this will be great. So as, as you know, obstructive sleep apnea or we'll call it OSA, so we can save some time here. Yet It's highly prevalent in people with obesity. Yet, it's under diagnosed, under treated. Right, So the, the SURMOUNT OSA program, it was designed, Oh, and you know what, just give me some background information here. I'll hand off to you as the expert. But it was to look at Tirzepatide and, and its effect on sleep apnea. So, what was the rationale behind developing the study and, and what you all were looking for?
2:01
Trice: Sure. Well, I think you hit the nail right on the head. You know, there are other clinical trials and studies that have shown that weight loss is associated with an improvement in the AHR. The apnea hypopenia index, the value we use not only to diagnose but also to determine the severity of obstructive sleep apnea. And with some of the prior successes with our compound Tirzepatide in the area of obesity, we look to see could it have an impact on patients with an obesity as well as moderate to severe OSA. So the goal was really to try and have address a dual burden, both the metabolic burden and the respiratory burden at the same time by addressing a root cause and in this case being excess adiposity.
2:41
WEBER: Yeah, very good. So for the study, what criteria were used for participants?
2:47
TRICE: So we focused on adult patients in the SURMOUNT OSA clinical trials. These are patients who also had to have obesity. So a BMI of greater than or equal to 30. They had to try it and lose weight at least once and have moderate to severe obstructive sleep apnea, which was an AHI of greater than or equal to 15 events per hour. And that was confirmed by polysymnography or you may consider in lab testing. In the clinical trials, home sleep testing was performed. However, when it came time to do the analysis, we relied on the gold standard which is currently in lab polysomnography.
So this SURMOUNT OSA program is actually 2 trials. The first trial included those adult patients with obesity monitored severe OSA who tried to lose weight at least once, who in addition to diet and exercise could not be on PAP therapy. And this randomized either get to Tirzepatide or placebo.
And then there was a second study, very similar, however, in this case these were adult patients beginning with obesity who tried to lose weight, monitor severe obstructive sleep apnea, who were on PAP therapy and again got diet and exercise along with either Tirzepatide or placebo.
We excluded some patients from the clinical trial, like those who have type one or type 2 diabetes, patients who had planned or prior surgery for obstructive sleep apnea, complex ear, nose and throat surgery and a few other criteria as well.
4:05
WEBER: So a question I often get with these medication clinical trials is what does diet and exercise mean?
4:12
TRICE: It's a great question. And this of course, this is a very difficult thing to kind of monitor in the in the real world and even in a clinical trial setting as well.
But in this case, the diet had to have a reduction of 500 kilo calories and exercise was self reported by the patient every week they were looking at reports.
4:30
WEBER: I think that's pretty similar to some other trials. All right, very good. And So what was, the hypothesis, the theory, what was how was Tirzepatide expected to influence OSA pathophysiology in the study?
4:47
TRICE: Well, again, we know that again, excess weight is associated with an increase in AHI and conversely that when the weight goes down, the AHI also tends to improve.
And because of that excess risk, we presume that maybe some of the upper airway excess adiposity, the increased collapsibility of the upper air way, the kind of reduced ventilatory control, all may improve as well as the AHI in patients who had moderate severe OSA and obesity.
Now Tirzepatide is a dual agonist. It's not a single agonist. It works on both GLP-1 receptors as well as GIP receptors to target both appetite and glucose metabolism. And so that reduction in weight can lead to maybe some synergistically improvements in OSA outcomes
WEBER: and, and what were those outcomes and what were the key findings that that you want our audience to take away from the SURMOUNT OSA trial?
5:39
TRICE: Absolutely. There's always primary in this case also secondary primary was that in both study, one of the patients who had PAP therapy who got Tirzepatide, there was a reduction in AHI that was significant compared to placebo.
In study two patients who had PAP therapy and Tirzepatide, again diet and exercise, in both trials there was a significant reduction in AHI when compared to placebo and what a substantial proportion of those patients actually achieving clinically relevant and meaningful improvement or OSA remission.
So an AHI of less than 5 or an AHI of 5 to 14 with a normal upward sleepiness scale score, which is again kind of used across multiple studies when you're looking at obstructive sleep apnea severity.
6:22
WEBER: Yeah. I'm curious if you know that the participants who were not on PAP therapy, do we know why they weren't on PAP therapy?
6:30
TRICE: So there's a host of reasons. So the patients could have never tried PAP therapy or they could have been intolerant to therapy. What was outlined in that study once that they had to be off of it for at least four weeks prior to enrolling in the study and then agreed to not resume PAP therapy during the clinical trial. That's to not confound it.
6:47
WEBER: Very good. And then between those two groups, the groups that were the group that was on PAP therapy and the group that was not where there significant differences in the outcomes,
TRICE: well, in both groups, in both clinical trials, I'll say instead of both groups.
So I don't want to confuse practitioners. I think that these are the same groups in one trial because we don't like to look across clinical trials. But in study one, the patients not on PAP therapy who got Tirzepatide, there was significant improvement. And also in study two, those on PAP therapy. So whether or not a patient was on PAP therapy, it's kind of difficult because it wasn't done in one clinical trial, but two different trials, both had very similar outcomes, significant improvement with Tirzepatide as compared to placebo in the patient's that got diet and exercise.
7:27
WEBER: OK, very good. And you may have mentioned this, but just to, to emphasize it, what was the average reduction in AHI across both studies?
7:37
TRICE: Across the studies was around 15 to 20 events per hour with a baseline of around 50. Now I think the key to take away here is that that's an average. So that doesn't mean that everybody came in with an AHI 50 and had a reduction of 20 down to 30, but it was an average reduction, which is a significant change in in both populations of patients as long as they were getting study drug, diet and exercise when compared to placebo.
8:01
WEBER: So I hear this all the time in my clinic. And, and I would imagine maybe you have heard it and, and our audience members also, some people don't like PAP, right? Some people love it, a lot of people don't. So, you know, I'm getting at patient reported outcomes. I know that was looked at in in these studies. So what did that data show?
8:24
TRICE: So it's great that you mentioned that because you know, as you said, there are patients who do great on other therapies and this was not designed to say this is superior or not inferior to another type of treatment. It's another tool in the toolbox. But what's really important is to listen to what patients are telling you. And in both study one and study two, we know that patients reflected having better sleep quality, reduced daytime impairment, which is I think is also crucial for how patients feel. And they were not only statistically significant, but also cleaning meaningful when you look at different thresholds.
So these are validated study thresholds when we're looking at how patients report outcomes in clinical trials and in multiple different nationally known kind of thresholds. Patients reported improvement.
9:08
WEBER: Yeah. So that's great to hear because I mean, we all should care about the the patient's reported outcome, right, And how they're improving quality of life or how it's affecting quality of life, the promise scores. So patient reported outcomes improved. Was there clinical relevance to that? And you can tie that in with the rest of it.
TRICE: There was there was clinical and statistical, you know, from a statistical standpoint, these are again validated studies that have been done with FDA guidance in the past.
But from a clinical standpoint, these are a certain amount of changes considered clinically meaningful, which means patients actually say there's a benefit to that. And both of these were seen in study one and study two in patients with Tirzepatide. So not just numbers, people reported better in a range that was clinically meaningful.
9:55
WEBER: So the, the AHI improved, the patient reported outcomes improved. Did those correlate at all, the AHI and the patient?
10:05
TRICE: That's a great question. Great question, doctor. Yes, there's actually a moderate correlation between those PROs. We call them our patient reported outcomes and the objective measure.
Since PROs are more subjective, what somebody tells you and AHI is a measurement that can be repeated and the patients with greater AHI reductions tended to report better sleep and less impairment, kind of reinforcing that clinical impact. As I mentioned that AHI was really that primary outcome, but there were multiple secondary outcomes like the patient reported outcomes and others.
10:36
WEBER: So we're throwing around a lot of letters here. So I have a question about, about one that was in the study or several letters.
10:42
TRICE: Sure.
10:42
WEBER: MWPC What is that?
10:46
TRICE: So MWPC stands for meaningful within patient change and it's a threshold that helps interpret whether a change in that patient reported outcome score is meaningful to that patient.
So for example, in the SURMOUNT OSA clinical trials, we anchored that meaningful within patient change to another scale that has known endpoints around sleep quality and fatigue. And this is an approach that the FDA has given guidance that enhances the kind of interpretability of those patient reported outcomes. So that each study is not just kind of doing it on their own, it's kind of anchored or something that's already been validated and proven before, right.
11:25
WEBER: So we, I think, you know, a lot of providers are familiar with to some degree that the STOP-BANG score, right, Screening for sleep apnea. You know, I, every new patient that I see in, in the obesity medicine clinic, we, we screen for sleep apnea with the STOP-BANG score. Is that similar at all to this PROMISE questionnaire and tool or talk to me about the differences or similarities?
11:46
TRICE: So the PROMISE SRI and the PROMISE SD and those are kind of acronyms, PROMISE being patient reported outcomes, SRI sleep related impairment, SD short for sleep disturbance, are again these kind of federally validated patient reported patient outcome tools that you can use across multiple different disorders. And they have been validated of course. And as you mentioned in the clinical setting, providers may be more familiar with things like the Epworth Sleepiness Scale score or the STOP-BANG, which are more diagnostic, diagnostic or kind of screen focused. But these Promise instruments assess kind of the real lived experience of the patient in terms of sleep impairment and its impact on daily life. And they're especially useful in evaluating treatment benefit from a patient's perspective, not so much from provider's perspective.
12:37
WEBER: Yes, that that leads me kind of down the healthcare systems route here because as an obesity medicine specialist, I and, and my colleagues, we've been prescribing these medications right, for obesity. And now there's this approval from moderate to severe sleep apnea. We screen for sleep apnea, but the Sleep Medicine teams treat sleep apnea with, with PAP potentially. So how, how do these two groups work together? Who should prescribe it? Who should screen? Who should diagnose? Do you have any, any thoughts or recommendations? I would absolutely like to know.
13:13
TRICE: I, I think this is kind of how do you bring it home? And it's, it's a fantastic question and this is not the first time we've heard this question. I think what's important to realize, as you said, there are multiple kind of stakeholders when you look at treating this disorder. So from obesity medicine specialist to sleep specialist, primary care physicians, ear, nose and throat, other specialist, bariatrics and each hospital system or private clinic that can be a variety of different practitioners who kind of take care of this disorder for patients. I think what's the most important thing to realize is this is the first of its class kind of dual agonist drug and it improves weight loss and AHI. So I think ultimately what behooves for us as providers is to figure out amongst ourselves who's going to take care of the patient. And it may require some collaboration that maybe hasn't been there in the past instead of maybe a handoff and saying, hey, well, you all have capacity or we don't. We tell practitioners that's really for them to kind of figure out what works for their particular system along with the patient.
But recognizing that collaborative approach is usually better, reaching out to those kind of specialists and those experts in your particular area, whether that's obesity medicine specialist or sleep specialist or combination of the two. Try to find out what's better for the patient, not just on paper, but realistically what's going to help them. And we know that an integrated approach to managing obesity and sleep disorders can potentially reduce the patient's risk for other downstream things like cardio metabolic risk as well. So it really helps to just have this conversation with other providers and figure out what's the best based on where you are right now.
14:40
WEBER: Perfect, very good, thank you. So from an obesity medicine and obesity treatment perspective, we have a pretty good idea how long someone needs to be on Tirzepatide for. How about if we're using it for obstructive sleep apnea? I know the study wasn't looking at this in particular, but if you could comment on that.
15:00
TRICE: Sure, great question. And as you said, the study wasn't particularly looking at that one. So we can't comment on that specifically in in the realm of this clinical trial. But I think this is where, you know, we still get to be clinicians and we have to decide when is appropriate follow up, not only to see response to therapy or what's appropriate therapy when a patient may be well enough controlled that therapy is either no longer indicated or again a change in therapy. So whether that's, you know, a holistic approach and lifestyle changes, Weight Loss, Diet, exercise or changes in other therapies like Tirzepatide or other options for patients with moderate to severe OSA and obesity. I think what's exciting is this kind of a new era where we know that treating obesity can have such dramatic impacts on comorbidities like OSA and other disorders. And it's kind of an exciting time, little disruptive, but exciting time for the field overall.
15:49
WEBER: Yeah, absolutely. And I guess kind of along the same lines again, not that the study looked at this, but you know, all patients who start Tirzepatide for moderate or severe sleep apnea and they want to stop their PAP. So I guess do you have any thoughts on that? What do you do redo a sleep study at some point or after a certain amount of weight loss or how do you handle that that question for patients?
16:11
TRICE: This is tough. You know, as a board certified Sleep Medicine physician, I have my thoughts, you know, as someone who's really kind of working in industry and making sure that I'm staying within those guardrails and not telling providers how to practice care. Just saying that here's one tool in the toolbox. And I say, if you're not sure and this is where your clinical acumen really comes in.
And one of the things it's done in this study, like most studies, is the ability for the provider, the physician or nurse practitioner or APP to really use their clinical judgement as the patients not only response, but possibly even side effects.
Thanks again, doctor, where we're so excited to be here and just have the opportunity to really, you know, talk with your members and you know, as clinicians, you know, industry partners, We know that this is an exciting time. It's a new treatment modality in a in a space where there hasn't been a lot of change. It gets practitioners another option to really kind of give their patients with obesity and moderate severe obstructive sleep apnea, another option that can address the root cause. I think the biggest take away is, you know, for the practitioners out there, have conversations with your colleagues, figure out what works best for you. Don't just, you know, hand off to another provider and say, it's not my problem because ultimately, the patient that we're all trying to take care of. And it may behoove us to work a little harder, a little differently, outside of our comfort zone to make sure that we're giving them the best options possible.
17:26
WEBER: All right, again, thank you so much, Doctor Trice, for your time and your input. It's been a pleasure. And thank you to our listeners also for joining us on this industry insights episode of obesity, a disease. We look forward to having you with us again soon.
