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Conversations in Pulmonary, Critical Care and Sleep Medicine by the American Thoracic Society
[00:00:00] non: You are listening to the ATS Breathe Easy podcast, brought to you by the American Thoracic Society.
[00:00:18] Amy: Welcome to the ATS Breathe Easy podcast. I'm your host, Dr. Amy Attaway. And I'm very excited to be here to discuss the URA trial, with Dr. Paneer and Heather, who is an asthma advocate. so Dr. Paneer, he is vice Chancellor for translational medicine and Science at Rutgers University. His interest include the cell, cellular and molecular mechanisms at regulate airway, smooth muscle growth in asthma and COPD, and he also co-led the Pura trial, which we'll be talking about.
We will also be speaking with Heather. she is an asthma advocate. She has discussed her personal journey with asthma before, including a near fatal [00:01:00] attack at age 11. and outside of advocacy, she works as a hospital software builder and once showcased her talent on American Idol. so welcome to you both, for being on the podcast.
we're going to be kind of diving into discussing the Pura trial. So this was a fully decentralized phase three B study evaluating Air Supra, which is a combination of albuterol and budesonide as a rescue therapy in patients with mild. Welcome to you both. I think Dr. Pener, we kind of wanted to start and kind of hear what your thoughts were on the rationale of the stor of the study, given the historic use of albuterol alone for mild asthma.
[00:01:42] Rey: Yeah. So, thank you so much. and this is a, a. Extension of the previous, two studies that were registry studies for the approval for the approval of AR supra and the management of asthma as an acute [00:02:00] medication. This is a big deal because if we look. Historically at new rescue therapy, it was about 50 years ago, five Oh, that we had had a novel new approach to rescue therapy, and that was back in the day.
It was theotropium back then. but we've had nothing since then. We've had derivations of mimetics like albuterol, but this. Is a game changer. And the reason this is a game changer is we're combining an anti-inflammatory and a beta agonist as rescue. So. For my patients, they really want to control their disease.
So what better way to control the disease than giving the patient a combined rescue inhaler of an anti-inflammatory? Budesonide with albuterol that makes the patient feel better, [00:03:00] but they're also able to control the inflammation on demand. So in the registration studies, those studies were, for 18 years and older.
This study extended that into, into the mild asthmatics, whereas the others were the, moderate to severe asthmatics. And we even find in those patients with the most mild asthma that the drug works. It works by decreasing symptoms. Decreasing exacerbations. So this is a new kind of rescue therapy that could benefit not only the severe asthmatics and moderate, but those with even intermittent and mild asthma, improve their outcomes and give them the ability to control their disease.
So in a nutshell, that's what this did. You did mention that this was the first, minimal touch decentralized study, which is a. [00:04:00] Again, a game changer in asthma where. No study patient was seen in a tertiary care unit or in a clinical research unit. These studies were all done in the home and it was a, wonderful study.
Had great engagement of thousand patients, and this is a wave of the future as we think through how do we get patients more access to clinical trials to improve outcomes.
[00:04:32] Amy: Yeah, that was, I thought that was really fascinating. And I think when I, when I think of an asthma, when people with asthma, a lot of them are younger, they're tech savvy.
so I think having, I thought that was like, not only was the, the treatment innovative, but the design, to me, it seemed like you were kind of hitting two birds with one stone. But I, I thought that was really. Fascinating. We wanna ask you a little, a little bit more about the de the decentralized aspect though.
Was there any [00:05:00] drawbacks to that? Anything you learned given it's so kind of a new strategy?
[00:05:05] Rey: Well, you know, being first is great except when you're first, so there's always challenges, right? So you're rolling out a study nationwide. Into people's homes, not into professionals who do this day in and day out for clinical trials, so they understand sort of the notion.
so, you know, the ch the, the opportunity here was to be able. To resonate with the individual to understand the practical aspects that you need to hit the marks for, you know, when data needs to be acquired, using electronic monitoring, approaches like questionnaires and surveys and be available for the calls.
So that is always a challenge, I think, to perform such a study [00:06:00] nationwide, we have to take into the, account. The state specific regulations on clinical trials, you know, we think the, you know, we're the US and we can do this, but each state actually has regulations in the use of experimental medications.
So how do you now take a study that you're gonna roll out, in a minimal touch, decentralized way to states, all of the 50 states that have different regulations. So I think that. Is the major challenge. It'll be a challenge for all of us as we embrace the idea of decentralized, critical, clinical trials.
But it's also the opportunity. If we can do this more often, then we should be able to decrease the hurdles, making this easier in the future, and allowing patients to enroll in clinical trials that helps their own outcomes.
[00:06:59] Amy: So we [00:07:00] have, Heather here, who has, you know, she's a asthma advocate. She also has asthma.
Were, were you in the, the trial? Were you a part of the D Oh, okay. I was not. I, okay.
[00:07:12] Heather: I
[00:07:12] Amy: came
[00:07:12] Heather: to air supra via my pulmonologist just recently.
[00:07:17] Amy: Oh, okay. Okay, great. Well, yeah, we're gonna go back to that, but I was just, I was just curious if you had any perspective on the decentralized design. So again, I think that's really fascinating.
The, um. The virtual aspect and seems like it's, it is hard, I think, to be the first at anything. it was exciting though that the study had an early termination, due to efficacy. and so, and there was, can you talk a little bit about that, like how it's.
[00:07:48] Rey: Yeah, so you know, many times, many times when you do clinical trials and, and I've been involved fortunately in many, many of those, you know, you have to go through the entire length of the [00:08:00] study, and complete it and then sort of lock the database and then examine the outcomes and see where you better than standard of care, right?
In this case, it was a comparison to albuterol versus albuterol budesonide. That is air supra. But in some instances we get it so right. And we have such stunning outcomes that it's hard to. Randomized patients to a, to a drug that's could be inferior. In this case, it was albuterol compared to air supra.
So you know, the study had an early stop because the data was so stunning. You know, I wish every study clinical trial was like that. We get it right. Not all the time our studies stopped, but in the past decade, there's many, many studies where the therapy was so profoundly better than standard of care versus [00:09:00] placebo, that it was unethical to continue to enroll people in the placebo or the standard of care arm because you got a drug that works so well.
So that, that was really refreshing, exciting. And it even showed an improvement in outcomes over the phase three study that compared albuterol to albuterol budesonide combination. So not only did we, show efficacy early, but we showed. And efficacy. That was actually a bit better than that. That was seen in the phase three trials.
This was a slam dunk. You know, it was really exciting and patients are gonna benefit.
[00:09:45] Amy: Mm-hmm. Yeah. And I think we, we were gonna, we were gonna talk about how this, the implications for patient care and maybe also the asthma guidelines, but I think, so Heather, can you talk a little bit about. Like your journey, how you said that you, you were prescribed the [00:10:00] medication and how, how you it's been for you?
[00:10:03] Heather: Sure. I'm, I'm a lifelong asthmatic. so I've actually been asthmatic technically since birth, but they, back in the eighties, they did not diagnose right away. So I was diagnosed in 1990 at age five. so my journey has been a really long one because I'm about to be 40 and, I just recently came to Air Supra.
It was the first medication that a pulmonologist said, it's gonna do this for you, and it actually did it. And so I was just blown away because I, you know, when you're used to your asthma being a certain way and behaving a certain way every year and you know what to expect every year, it's kind of, it's, it's almost.
You don't wanna hope for better when this is just the norm. So when I got this inhaler and things became better, I was shocked, knowing that I made it through one of the Texas flare up [00:11:00] seasons and I did not get sick. That was the first win in my category, you know, and I have check boxes of my little categories of wins, and to me that was like.
Exciting because, you know, you wanna be part of life and as an asthmatic sometimes you feel like you do live life on the sidelines. And this was the first time that getting a medication that allowed me to be part of the fun instead of on the side was just wonderful. And hearing, Dr. Panter, what you've said about how wonderful it was for everybody in the, in the, clinical study, I, I can only echo those sentiments because from the first day, the first time, it was different.
It was different in a great way. and so I just, I've been excited to continue to take it and I'm actually excited to tell people about it because whether you think your asthma's stuck in a rut and you've been on the same treatment plan for so long, really just take that step. I was a little nervous to take that step and I'm really, really glad I did.
Now.
[00:11:59] Rey: [00:12:00] How important is it for you to be able to control your disease on demand? You're controlling it. You've been told to take your maintenance therapy right day in and day out, but the maintenance therapy can only control some of the symptoms, especially when you approach seasons where there's a lot of triggers or you get a viral infection.
Knowing that your rescue can now affect the change on inflammation, whereas before it was a bandaid. Does that feel better to you also,
[00:12:31] Heather: not only to me, but to my whole family. I do have children, and my children, quite frankly, used to watch me go to the er, go to the hospital. They've seen me admitted more times than I care to admit sometimes.
but this was the first year that I, I actually forgot that it was a flare up, like it would've been a flare up. And we were out walking and I said, it's March. My husband looked at me kind of funny [00:13:00] and I said I didn't get sick. And it was the first just like realization, just this moment of clarity and it was so nice to not have my son and my daughter look at me with sad eyes anymore.
And so for the first time it felt like, you know, mom can be whose mom's supposed to be, and this has just been a life changer for me. So yeah, it's definitely nice to not be Heather with asthma, but be. You know, yeah, I have asthma, but Heather's in control of it now.
[00:13:32] Amy: That's wonderful. No, I, and, and I think especially thinking about how it impacts your family, how, how it impacts your kids, and, I think we, for, you know, I think a lot of times we're, we're so worried about other people, right.
And that, but then it turns out like how much your kids can be impacted or, or they can internalize things. So, no, that's wonderful to hear. I, I, and I do think it's, so were you prescribed the medication by your pulmonologist, or do you have, was it your [00:14:00] primary care?
[00:14:01] Heather: It was my pulmonologist. Okay. I had, I had just recently switched to a new pulmonologist as well.
Mm-hmm. And and usually that is kind of scary for me because when I walk in sometimes they say, let's try to spin the wheel on meds for you and. When he said this, I kind of looked at him and he said, no, trust me. This one's got really good, you know, trials, it's got really good ratings. Patients are saying wonderful things about it.
And I said, I will trust you. And so I took the medication and it's been almost a, a full year now, and I, I don't wanna look back at this point. I don't wanna go back to my little red inhaler that we all know and love.
[00:14:41] Amy: That's great. Daca. Yeah, yeah. No, I, we, it's interesting to me because, I think the implications for this study was in mild asthma.
So I think a lot of times as a pulm, as a pulmonologist, I'm not seeing the patients who are quote unquote mild asthma. a [00:15:00] lot of times those are primary care or the emergency room or urgent care. So, it just seems like a, the study itself was a great opportunity to. Think about reaching out to our colleagues in those, you know, kind of the front line, of asthma care and how we can, how we can reach out to them and so that they understand that there's, you know, these new therapies, new guidelines, things we should be thinking about.
Can you tell us a little bit about like, the whole journey? It's been a long journey, right? You know?
[00:15:29] Heather: Sure. Yeah. I was actually, I was born premature. I was born with collapsed lungs, and so that started my, respiratory illness right from the very beginning. my mom, only had me, so I, I was her only child, and so, she noticed that I just could not breathe.
I mean, just really, that's what she used to say. I would, she couldn't put it into words saying that I was wheezing yet, because she had never had an asthmatic child. She had never had an asthmatic sibling. I was the first one in the family that had asthma. So for her, she [00:16:00] really was just watching it all unravel, and then she just kept going to, we had a, a, like a primary care doctor that we would go to repeatedly and finally she said when I was five, she said, I think she has asthma.
And we started a very, arduous process at that point. I did get an allergy and asthma specialist at that point. I did start allergy injections at age five. The reason why I say it was arduous was because my very first medication I had to swallow. I didn't swallow pills yet, and they opened it in. My mashed potatoes and mashed potatoes are not supposed to be crunchy, so that's why I could not, I did not enjoy that.
but as things developed, I, I did take allergy shots subsequently for. Oh gosh, we were at six years and then my mom got transferred overseas, so we went and lived overseas for a while and that completely changed my asthma and unfortunately that's what led to the near fatal attack in, when I was 11.
And unfortunately, I, I don't think we could have prepared for [00:17:00] that because it was the mid nineties and there really wasn't a lot of. I don't think we communicated weather as well as we did now, perhaps, or even, you know, we're cognizant of allergens in the air and how travel really does impact your asthma.
And so when we lived there, of course my asthma just got consistently worse and worse and worse. We subsequently transferred back to the states, after being there for three years and my asthma found a new pattern again. I ended up kind of being on the same, you know, two year, two times a year. That was my flare up plan, and that's what I considered controlled.
I mean, I'm using air quotes here because. Controlled. Really in my mind now, I think means no flareups, but at that time it was, that was two times a year and that's what I had. I considered that to be pretty normal until I, I actually got married, had my first child. Everything was fine with my asthma, but my second pregnancy really drastically affected my asthma.
Did not know that was a possibility either. And so my son is now 10, [00:18:00] but between. His pregnancy. And now I had had uncontrolled asthma for 11 years. We tried everything and I, literally went from, you know, biologics. I tried four out of the, or excuse me, three out of the four biologics I tried, so many different types of therapies along the way and I just really tried to listen to my physicians as much as possible.
But it didn't matter what we did, things weren't working. And, and so. I have been on steroids and antibiotics for every four to six weeks for the past 11 years at this point. And so it's done a lot of damage to my body. You know, my bone, my bones of course, have broken down a little bit. but start since starting Supra, I have a countdown, or excuse me, a count up now, and it's days since prednisone, and this is the first time in 11 years that it has six.
It has gone past six months. Wow, that's amazing watching. Wow. Yes. I love watching it go up now. And so, you know, the longer we get out from [00:19:00] prednisone and the longer we get out from those lifesaving measures and you know, of course not having to explain to my daughter, I just can't breathe, but it'll be fine.
And so, you know, things like that along the way. So it's been a journey for sure. But I'm glad that we ended up here.
[00:19:15] Amy: I, that's one of my favorite things, is when I, we somehow we can break the cycle of exacerbations. It can be so hard, but I think it's just such an amazing feeling and for you, for, for your doctors when you can do that.
So, knock on wood, but that's amazing. so, so, um. I guess we were, say this, one of the things, we actually spoke with Dr. Leggo at University of Michigan, one of our previous podcasts, but we were thinking like what the implications were for air supra and asthma, and then maybe in other lung diseases. So we kind of wanted to think, ask what your thoughts were, Dr.
Penit Terry, like what are kind of, what's, what's the future hold? And then what does this mean for other diseases?
[00:19:57] Rey: So, it's a great question, right? [00:20:00] So in all diseases where a rescue inhaler could be used, especially this we're talking about obstructive lung disease, obstructive lung disease is asthma, COPD, also chronic bronchitis, emphysema, and even adult non CF bronchiectasis.
You know, these are diseases punctuated by exacerbations, and flares. So. If you were to reach for an albuterol rescue the question. Are these other diseases amenable to the use of a combination ICS Albuterol? Now to be transparent and fair balanced, none of those other diseases, is AIR Super approved for its use.
So that would be off label. I think, I'm sure AstraZeneca is excited about pursuing indications in these other diseases that'll give opportunities, to patients. each disease [00:21:00] that I mentioned is a little different, but I do wanna come back to something Heather mentioned and it's so important when I see my patient.
With asthma who are steroid dependent OCS or oral corticosteroid dependent. They hate oral corticosteroids, but they also know their life threat. their life saving. So. Indeed what Vitu showed, none of those patients were on chronic oral corticosteroids, but they showed a 50% decrease in the amount of prednisone necessary in the observation time.
How did that work? Well. Every exacerbation patients get steroids. If you decrease the exacerbations, then what you've ultimately done is decrease the need for oral steroids, and therefore you see a 50% decrease in the oral corticosteroid burden. Steroids my patients hate. It's the diabetes, the mood change, the [00:22:00] fluid retention, the cataracts, the hypertension, the truncal obesity, that all of these things are associated with oral steroids, so anything that can decrease exacerbations that require oral steroids.
By extension means we decrease the exposure of the patient. So that's a real, that's a, that, that, that's really important for my patients. And, and we heard from Heather, who eloquently told us, she knows steroids are necessary but hates them.
[00:22:32] Heather: Mm-hmm. Very true. My husband isn't a fan of them either.
[00:22:39] Amy: Oh, that's, I, I mean, I, I think I totally agree with you. I think that, you know, there's, it'd be interesting to see the indications and other diseases. I, I think CI think COPD in particular, we need to be a little bit better about phenotyping it, because it seems like some have this inflamm, you know, this inflammatory phenotypes.
Some don't. but I do, [00:23:00] and I mean it's, I think asthma has just moved so far, into like a way, you know, things that will treat. Asthma without steroids. It's just so exciting. All these new biologics, these new inhalers, so that's, I think asthma is just. It has, you know, the last 10, 15 years. It's kind of, the whole field has just been revolutionized, so That's so exciting, I'm sure for all of you.
[00:23:23] Rey: Yeah. And Amy, what you're talking about is the ex extension of this drug laterally into other diseases, but I'd also suggest probably the. Thing that should be examined is can we get children on this drug? Mm-hmm. Because I think if we can extend its utility has to be proven. And this drug is not approved right now for under 18, but it would be wonderful if patients.
younger patients have access to this drug, who could intermittently use an ICS LABA to [00:24:00] control their disease without having to be on maintenance therapy potentially. So I'm excited about that potential. The studies that all the studies were done. In 12 and above, but the studies weren't powered to be able to determine efficacy in the 12 to 18 group.
So we don't, we can't, they, that is AstraZeneca can't claim to, have an indication or a utility in that group. So studies have to be conducted, but I am. Confident that those studies will read out positively so that our patients, our children with asthma can benefit from this rescue inhaler.
[00:24:41] Heather: Mm-hmm. Yeah.
I think next step I have to, oh, go ahead. Oh, sorry. I was gonna say, I have to admit, that does intrigue me. My son has asthma and he is 10, and he, he does take a maintenance inhaler right now, but I, I believe he would be so much better off if this was. Accessible to him. And so I, I feel [00:25:00] like he's going to outgrow it, Lord willing, but I do think, you know, he, he wants to get on with his life too.
And so he's been slowed down a couple of times. Thankfully, not nearly as badly as I have, but I, I would be very interested to see how that, how air Supra can affect the younger guys now. 'cause I don't know, he's, he's there.
[00:25:20] Amy: Mm-hmm. And I think for you, so you've kind of been on this journey, you kind of know what to look for, you know how to help him, and so that's wonderful.
Yeah.
[00:25:29] Heather: Yeah. That's what my, my physician that took care of me during that pregnancy. each time that I got pregnant, I hoped that my child would not have asthma. And she said, you know what? If they are though, you're the single best mom to take care of that. And I didn't think of that at the time. My daughter did not have asthma, but when he did, and I spotted it immediately, and he.
Received a fire truck nebulizer for his first birthday. You know, I, I realized that he had it, and, and I was able to spot it. And so we've kept him. He's never been [00:26:00] admitted to the hospital. He's always been, you know, pretty controlled. He's only had two rounds of steroids his whole life, and we're, we're in a good spot with him.
But yeah, it'd be very interesting to see how Supra can help the, the kids underage. 12.
[00:26:16] Amy: Yeah. Yeah. I think, and then, then also that 12 to 18 age, seeing if that, if it will be approved for them too. Yeah, definitely. I just wanna thank you both for, giving your time to the podcast, Dr. Pennet, Terry and Heather.
Heather, thank you for telling us about your journey. and you know, I, I think we've had seen so many people improve the last 10, 15 years in a, in their asthma therapy, so I'm just. So happy that yours has improved as well. So, and thank you Dr. Pen Terry for, giving us your expertise and how the study design, it was a really fascinating study.
So thank you both for participating in the podcast. Thank you for having, Hey Heather,
[00:26:54] Rey: thanks so much. That's really brave to stand up. You're true hero. Thank you. [00:27:00]
[00:27:00] Heather: Oh, thank you. And I just from a, from a. An old asthmatic standpoint. I really loved hearing how the clinical trial went. That was really fascinating for me.
So that was really fun. Thank you so much for having me. I appreciate you both.
[00:27:15] non: Thank you for joining us today. To learn more, visit our website@thoracic.org. Find more ats, breathe Easy podcasts on transistor, YouTube, apple podcasts, and Spotify. Don't forget to like, comment, and subscribe, so you never miss a show.