All right. Good afternoon. I'm Ryan Weisvening, Vice President of Investor Relations for Medtronic. Thanks for joining us for our Structural Heart Investor Briefing here at the CRT Conference in Washington, D. C, and welcome to those joining us around the world on our webcast.
Before we get started,
go to the
next slide here, I want to note that we could make some comments that may be considered forward looking statements, and actual results might differ materially from those projected in any forward looking statements. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports and other filings that we make with the SEC, and we do not undertake to update any forward looking statements. I encourage you to go back and read the slide, and the slides that we are presenting today will be available on our website, which is investorrelations. Medtronic.com. Today's webcast event will last about an hour.
Nina Goodhart, Vice President and General Manager of Structural Heart, will make some introductory remarks and then Doctor. Peter Capitaine, our Vice President and Chief Medical Officer of Structural Heart, will also make a few remarks. And then following our presentation, Nina and Peter will be happy to take your questions. And we plan to wrap up around 2 p. M.
Eastern this afternoon. So Nina, do
you want to get us started?
Well, thank you all for joining us here. We don't usually do an investor have an investor discussion, I'll call it, at CRT. But with ACC coming thank you. With ACC coming and the focus of ACC, of course, we believe will be on our late breaker trial, both our TYRX late breaker and our EVOLUENT low risk late breaker. We thought this would be a great opportunity to talk about things other than low risk.
We've seen a huge amount of momentum in our TAVR program, and so we wanted to share a little bit with you about what we're seeing and why we're seeing it and be able to answer some of your questions. Clearly, with ACC just a couple of weeks away, we are not going to talk about low risk. I don't think any of you expect us to do that. But what we thought we would do is just walk you through the study design. We I think as some of you may know, we have a Bayesian design essentially that allows us to take our 2 year endpoint and take an interim look at that at 1 year.
Professor Kapitan will talk a little bit more about that. But the design is just a little bit different than the traditional trial design. So we thought it might be helpful just to walk you through that prior to you all getting to ACC. So essentially here, what you see is that, we as I've said, we're really seeing very, very strong momentum in the TAVR program. And we think that that's attributable to a couple of things.
1st and foremost, the markets that we operate in, about a $5,000,000,000 market we're projecting by fiscal year 'twenty two growing in the mid teens in that same timeframe, primarily driven by new indications, things like low risk, assuming the trials are positive, bicuspid, again, assuming our trials are positive, but also penetration into our current indications, our high risk and our intermediate risk indications. We've been seeing very strong performance from the valve. We've been very, very pleased with the performance of the valve. We've been talking a lot about our hemodynamics. We're going to talk a little bit about that today because we think that's been a primary driver for why we're seeing share gains, and we'll talk about that.
We think that as we've educated physicians around the world about the benefits of this valve design and the hemodynamics that it offers, physicians are really seeing that as a benefit for their patients and thus are using the CorVel platform more and more across their spectrum of patients. We're seeing excellent procedural outcomes. We've got a strong PDL solution, as you know, and this valve is recapturable and that's a benefit that physicians have continued to see as they've gotten more and more experience with the EVOLUDE program. And then we'll talk a little bit about our pipeline. As Omar mentioned in our last earnings call and as Mike Coyle mentioned about CDG, this may be the strongest pipeline that we've seen at Medtronic in a really, really long time.
The same is true for our structural heart pipeline, extraordinarily strong, both on the TAVR side, and we'll talk just a little bit about where we are with our mitral program as well. So we've talked a bit about share. And I think in the last couple of calls, we've talked about our share growth for the Evolut program. And this is something I think that we've been very, very pleased with, very proud of. We have a share position.
I'm not sure that he's always aware of this, but we have a share leadership position in almost all of our geographies, all of our regions with the exception, of course, of some of the big ones, the U. S. And Japan in particular. We are seeing, however, share gain in those two geographies and again, primarily driven by the benefit of the valve. I know we've gotten questions about whether or not any of that share gain is coming from any price supplies or any aggressive pricing programs that we put in place.
And the answer to that is no. Our pricing has remained stable. We've been very pleased with the price stability of the market and of our program. And so the share gain is truly coming from the valve and the benefits that the valve provides. And so when we talk about why we're gaining share, we get a lot of questions about why we're gaining share, and it's really primarily about the hemodynamic story that we've been talking about pretty extensively across the globe.
And essentially, what we see here is that size matters and being big is a good thing here. And I'm going to let Professor Kapitan talk you through what the hemodynamics are, why they matter and why we're seeing such strong hemodynamics from the Evolut platform. As Ryan said, Professor Kapitan is our Chief Medical Officer for our coronary and our structural heart business. He's a cardiac surgeon out of Rotterdam, has been a key thought leader in this space for a very long time. I won't say how long, but a very long time.
So we were ecstatic when Professor Kapitan joined the Medtronic Structural Heart and Coronary Group. So why not let you walk through that? Thank you.
Well, thank you very much, Nina. Thank you all for joining us here for this meeting. Actually, it's an incredible journey. If I think back in November 2005, we did the first corveld implant in my center, in the Erasmus Medical Center in Rotterdam. And that time, it was a really collaboration between surgeon cardiologists.
We went on bypass. We used a heart lung machine to implant the first valves. The first three were using a heart lung machine. Then we did 2 with just left heart bypass. And then we also figured out that you could do it even without rapid pacing.
So if you think back 2,005 and where we are today, it's an incredible journey. Now we're doing those implants just on the local anesthesia, the patient is fully awake. And of course, the valve has changed as well. So it has been better performance what we see nowadays. And as Nina mentioned, I'm a cardiac surgeon by training.
So as a cardiac surgeon, we know very well about the issue of patient procedures mismatch. That actually means that if you put a valve in a patient where the orifice area is actually a little bit small on the small side. Of course, what we want to do, we want to release aortic stenosis that a patient has. So the area where the blood can go through the valve is too small. But if you implant a valve that is too small, then you don't really gain a lot of for the patients.
And I think the beauty of now is what we have seen out with Evolut R and Evolut Pro that we see this great hemodynamic performance of the valve. So a larger EOA actually means that you have more area so that the blood can go from the left side of the heart towards the aorta and then to the rest of the body. And it means also that the left ventricle, the work for the left ventricle is less. So what you see also that you get better remodeling of the left ventricle, and that's especially for long term follow-up is important. So in surgical data, we have already shown that actually if you have a a patient prosthesis mismatch or if the valve is too small for that particular patient, that has an effect on long term outcome.
So mortality even is higher in patients that have severe patient prosthesis mismatch compared to moderate or no patient prosthesis mismatch. And actually, what you see here on the graph is that the smaller the area gets, the higher the gradient. And of course, we're always concerned about gradients. When you see a gradient with an aortic stenosis, but you may also get a gradient when your valve is actually too small for that particular patient. So a larger EOA is important.
So we were figuring out with our superannular valve that maybe we have a better EOA compared to some of our competitors. So we were also very pleased actually with data that was published by an independent group by Becky Han, who's a very respected echocardiographer from Colombia, that they published the data. They used the data from the most partner trial and from our trials and to see what the hemodynamic performance was of our valve compared to SAPIEN. And what you see consistently over the different sizes of the valve, actually that the EOA, as you can see here on the upper one, is better. Evolut R has consistently a better effective ORBC air compared to SAPIEN.
And that results in a lower gradient with EVOLUT R and EVOLUPRO compared to the SAPIEN heart valve. Now what does this mean for patients? So you have a better effect of Orpheus area, your grade is lower, so your hemodynamic performance of your valve is better. But does that really translate in a heart endpoint? Well, it does.
So Harvey Hermann from Philadelphia has published the data to show that actually there is an impact also in transcatheter heart valve on the heart endpoint as mortality. And as you can see here in this graph here, you see that if you have severe patient prosthesis mismatch compared to moderate prosthesis mismatch or no mismatch at all, actually your mortality is higher. So I think this has resonated very well now with clinicians in the United States. If you implant a valve in a patient that actually needs a long term follow-up, that needs to live much longer than, let's say, the 85 year old, it's important to consider the patient disease mismatch and that you have a valve that performs very well. So I think that is really the beauty of the new platform that the hemodynamic performs is so great.
So having said that, we have done a lot of studies to show that our valves performed well. It started already with the NOTION trial. The NOTION trial was actually investor initiated study out of Denmark by Professor Sundgaard from Copenhagen. But the monitoring process, the analysis of the trial was all done and supported by Medtronic. This was already published in 2013 actually in a kind of all commerce study with a lot of low risk patients included in the study where we showed that actually the patient did very well with the TAVR device.
Now the study has been followed up to 7 years, and we see also still that there's a great result with TAVR. There's no difference with surgical AVR. And this is really a low risk mostly low risk patient population. Of course, when this study was being performed in Europe, Europe was a little bit ahead, of course, compared to United States. Then in United States, we started with Xtreme and high risk trial, randomized trial, 1 year endpoints and then followed by the intermediate risk trial, which we also called Sertavi.
That was a global TAVR trial versus surgical AVR randomized trial, a 1 year endpoint, and those patients will be followed up to 10 years. Both the Surgical arm and the transcatheter arm will be followed that long. And now, of course, we're all waiting for what the lowest trial will show us at ACC, so that is in 2 weeks from now, and that will be presented there. Then besides those trials, we also have the registries, which are extremely important as well. So there's you see here at the bottom of the slide 4 different registries, expanded use, a U.
S. Single arm study, 5 year follow-up on patients with a higher surgical risk. Then we had the FORWARD, real world registry, 1 year follow-up, multicenter European data on EVOLUT R. We had the forward PROS registry, the real world registry again, 2 year follow-up operation with all surgical risks, so this includes all patients. And then we have the bicuspid study, which is, of course, a little different than just risk profiles.
This is really focusing on a special anatomical subset of patients. So as you see, we put a lot of effort in those trials, generating evidence. And the good thing is also we follow those patients, and we also publish these data. And that sometimes not all our competitors do this the same.
Yes? That's why I'm trying to
Yes. Yes. So low risk what we see is at low risk patients, the incidence of bicuspid death is much higher than in the elderly patients. So if we move towards a lower risk patient population, patients will probably also be younger, and they will also have more bicuspid valves. So therefore, it's important to generate evidence that you can also treat patients with bicuspid valves.
In general, what we see is that patients who have 3 leaflets, which is hopefully everybody in the room has 3 leaflets that they already have, bicuspid patients have only 2 leaflets. And what you see is that actually it's a kind of congenital malformation of the aortic valve that they are more prone to calcification. So they get more often stenosis. But not only that they get stenosis, the calcium is also not distributed symmetrically. So there's sometimes big piece of calcium just on one side of the aortic valve.
And so therefore, it might be more challenging to treat those patients with packed with valves. And therefore, we think it's important to generate that data as well that our device also works in patients with paccus medulls.
So
just a question, yes. Yes, right. Yes, so there are challenging and less challenging bicuspid cases, absolutely. So you have bicuspid cases where you hardly see normally, what you see bicuspid cases is also that you see the start of where the 3rd lesion should have been. Those probably are a little bit easier than if you don't see any indication where actually nature, modern nature would have thought that their third lesion would have begun.
And the majority of patients, fortunately enough, they have good anatomy where you always see kind of what we call a RAFA, so the start of where the third leaf it should have been. And so we think that from the 50%, a lot of those patients can be treated with transcatheter heart valves. But to find out the right methodology to do it and the sizing methodology, that's why we do those studies. So if we think about low risk, we also want to look back a little bit to Certavia. Maybe you remember that the Certavia trial that we presented had what we call a Bayesian analysis.
And Bayesian is this kind of statistical methodology where you can use data to predict also outcome. You can actually have an earlier look that waiting until all patients have completed their follow-up. That's the beauty of Bayesian analysis. So you still have the same number of patients that you originally estimated that you should need for a trial, so it doesn't mean that your sample size will get smaller, but it allows you to take an earlier look at your data and to predict actually what the 2 year outcome will be for all your patients. So we had a similar statistical technique, Bayesian analysis for our Sertaghi trial.
And of course, what we did, we presented the Bayesian analysis that was published in the New Age Journal of Medicine. And we're trying to also have the FDA has given guidance on that we maybe use Bayesian analysis more often. But we also follow those patients until we had the complete 3 year follow-up. And of course, what was very interesting to see, did our Bayesian analysis predict what we saw in real life, you could say, so until we had the complete follow-up. And so these are the 2 curves.
You see here TAVR is the yellow line and surgical AVR is the blue line. This is the interim analysis from Certavi. So this is what you call the Bayesian analysis, and then this is what we call in statistical terms the frequentist analysis, So the real follow-up of 2 years. And actually, what you see is actually there's hardly any difference between the two. So the base analysis predicted exactly what the frequency of analysis showed as well.
That's important to keep in mind because now if we go to the next slide, you will see this is our low risk trial design. So LOWEST is a heart immune evaluation, again. So we also had in the previous trial, surgeon and Cardiolis had to agree that this patient could be randomized because both should be able to perform either surgery or transcatheter heart valve implantation. So when the heart team had confirmed that they thought the patient could be randomized, then there was a screening committee that would check whether all the inclusion, exclusion criteria were met. Once they were met, the patient was randomized, then the patient was randomized either to transgafen aortic valve replacement or surgical aortic valve replacement.
We allowed patients to also be revascularized. So you see the TAVR arm, we have 2 groups, TAVR only or TAVR plus PCI. And in the surgical group, we have surgical valve replacement only or surgical aortic valve replacement plus coronary evascularization. So we're all looking forward at ACC, the late breaking trial session. So it's at 8:15 early in the morning of Sunday in the main hall, the grade tent, session 404.
So there will be we will present our data. At the same time, Edward will present the data, and then there will be followed by a discussion. So we're looking forward. Probably, we'll all be there in New Orleans and discussion there.
Thank you. Rick Warren, Stifel. Just a couple of questions. On the data we're going to see at ACC, how much of the low risk trial was Evolut versus PRO? And just is there some way to talk about that?
And as we try to get ready to assess the PACER rate impact, I assume it's going to be less withdrawal. Yes.
Unfortunately, we're not allowed to deal with those data. Yes. All the data is actually from the lowest. That's why we have this meeting here to give you a little bit of an update on the design work.
I know, Vincent. I'll ask a today question. You talked about hemodynamics and the importance of it, and I've heard that over the last couple days here. And I'm not sure what I'm exactly asking, but if I reflect on smaller orifice and the hemodynamics are obviously better but larger, what's it mean for your smaller size implants? I mean, does this say something about implanting the choosing to implant a 23 millimeter valve?
And are there implications there that we should be thinking about going forward given the hemodynamic story?
Yes. So I think especially in the lower sizes, the smaller sizes, we have a major, major advantage over SAPIEN. There are even people that have called and said this morning, it's criminal to implant the 20 or 23 safety and heart valve nowadays. If you look at the data, the human demand performance of Evolus. So you really end up with a higher gradients.
And especially in lower spatial, you should think that if you have a gradient at rest of 15 millimeters or 20 millimeters of mercury when you exercise, that gradient goes up to 40 millimeters 50 millimeters or 60 millimeters of mercury. And so you have more cardiac output, so your heart is pumping more blood. And if you have an orifice that is too small, your gradient becomes more higher. And so that has an impact on your left side of the heart or young muscle. And so you get less what we call left ventricular regression, which means that your heart goes back to the normal state like hopefully we all have here in the room.
And so it has an impact on long term mortality, especially young patients because they exercise. They go shopping. They walk the stairs, etcetera. And then every time that you do that, your grading goes up, goes up to 30 or 40, and that has a major impact. And just one other
topic and I'll be done. Coronary access seems to be another very critical topic just as important as hemodynamics. Maybe talk about the Evolu and Evolu Pro and just how you all stack up in your opinion and what you're doing to make sure that subsequent generation valves have that access?
Yes. So the Corning Access, of course, is something because if you have a larger frame, people are afraid that your coronary axis might be an issue. It's also not zero with SAPIEN because the of the SAPIEN valve may be just at the coronary calcium as well and may also have a more difficult access. What we have learned also from a lot of cardiologists that have intended a lot of LEMS is that there are special techniques to get better coronary access. And so what we will also focus on to learn those techniques to other physicians as well so that they can have a better access to the coronary Ostea.
And of course, Nina will talk a little bit about our platforms and where we are going with the next generation. She will address this issue as well with coronary osteoarthritis. The other thing what I want to say is that sometimes, of course, it's very intuitive to think coronary osteoarthritis might be a problem. If you see how many patients actually need repeat revascularization after anortic valve implantation, it's a very low percentage actually. And we noted from surgical aortic valve replacements, which are mimicking the low risk trial population, there are not that many patients that need during a follow-up a repeat revascularization.
Okay. First, Nina, and then we will, yes, answer all the questions. Okay.
Thank you. So as we think about the platforms and the programs that we've got coming to address some of the unmet needs in the market, You're all familiar with the current Evolut Pro and Endeo Pro platforms that we currently have on the market. So that's what's giving us is really strong hemodynamic performance that Peter has talked about. Our next program coming forward is what we are calling Evolent Pro. That is and that will do a couple of things for us.
As you know, we have a wrap or a skirt on almost all of our valves that's led to some of this increase and improved performance. Physicians have told us that they are very pleased with the performance that the skirt delivers. We did not have that skirt or that wrap on the 34, our largest size valve. And physicians have told us that they would be interested in utilizing that doll more if it has that skirt. So we will be wrapping the 34 in this program and that will be coming somewhere in the mid fiscal year 2020 range.
We've also taken our profile down. So if you remember, when we started all these valves, we took the profile up by 2. We're now bringing that down to a 14 French size across the platform, so we'll take down the profile. And as we've talked about before, we've made an acquisition of an expandable sheet, something physicians have told us that they liked. That will be a 12 French sheet that will also be coming in that mid fiscal year 2020 timeframe.
Programs coming after that, we have not yet set timing for that. It's a program we're calling Evolut FX. I don't think that we've talked about that specifically here. It's a strong program for us in development. That's where we're really looking at improving the positioning of the valve and giving providing a little bit more visualization.
So putting some radio opaque markers on so that you there's a little bit more clarity when you're looking at where you position that valve. And that's something that physicians have also told us that they're looking at. So, we're looking forward to bringing that program into the market. And then next comes our what I would call our next transformative program. We have called that Horizon.
You will never see a product called Horizon, but that's the program name. And that's where we're looking at things to your point about coronary access, whether or not we can start to build valves that start to meet some of those needs. And so we're looking at things like taking the frame size down a little bit to provide better access to the coronary. We're looking at things like widening the windows a little bit to again potentially provide more access to the coronaries. And so that's a program I think we're pretty excited about currently in development, and we'll be talking more about that as we go forward.
I thought I talked just a little bit about Mitchel while you're all here. You all know where we are with Mitchel. We have talked, I think, pretty publicly about our belief that we're going to need a toolbox of approaches, if you will, as we think about mitral. Mitral being much more complicated than the aortic space, I think you've all seen that. We've indexed down hard, as you know, on replacement.
And so we have our current APOLLO program running, our Intrepid valve performing well. After TCT, as you know, we saw the COAP results. I think everybody was ecstatic about those COAP results. We were very pleased because I think what that told us was a couple of things. One is you could treat these patients.
We weren't really sure prior to COAPT and that we can treat them with device therapy, which essentially opens up, I think, a whole new market. Discussions around repair and replacement, our feeling has always been that if you can reduce MR, that's good. If we could eliminate it, that would be better, and that's been our focus on replacement. The trial is continuing to run. We've gotten some questions about as to whether or not we've seen any changes in enrollments, declines in enrollments after COAP, I have to say we haven't.
Physicians have remained really enthusiastic about this program. And so we're continuing to see that enrollment. These are hard trials to enroll. They're early trials. We saw that with COAPTIGENEL, a very long trial to enroll.
But we're pretty pleased with where we're going. We've had discussions with FDA on this program. They're also pleased with where this is going. So we'll continue to move forward. In terms of repair, we're also looking very, very strongly at repair.
We do have an investment that we've made in repair. Our program is doing very well. We're looking at some of the unmet needs in the repair space. Specifically, we think about things like ease of use. We think about lifetime management.
If you remember with MitraClip, a lot of times physicians are starting to see sales MitraClip come back. And once the MitraClip fails, there's no place else to go. You can't do a replacement in a sales MitraClip. And so we're looking at providing options that give physicians and patients more options once they have a mitral repair. And so we think the program we have is very is pretty differentiated.
We're not going to talk too much about it until we're a little bit further along. But we're excited and enthusiastic about what we see, and we're going to continue to move that program forward. So what you'll see from us coming forward is both replacement and repair technology solutions. And so I think with that, we'll close out here. When we think about structural heart, at least for Medtronic, we think about solutions for all four valves.
So you know we have a strong congenital program. Our HARMONY trial is continuing to run. That will be closing out very quickly. Our congenital physicians are really pleased about having a new option. We've talked about where we are in TAVR.
We're excited to see what the low results low risk results will look like. I think we're pretty excited about the fact that we started so much than our competitor in terms of getting that trial up and running and sort of be at the same on the same podium, I think, is a tribute to both our clinical team and our investigators. And I think that will be great for the clinical community to be able to see both of these trials coming forward as we move forward. And so with that,
oh my goodness, are there any questions?
Go to Bruce.
Sorry, just a quick question. Could you explain what you're going to be putting on at ACC in terms of the Bayesian analysis or the final frequentist analysis, what's going to be presented there?
It's the Bayesian analysis. And then
would you say what percentage of patients or?
Currently, we cannot say that. I mean, you will see, but it allows us to present data. That's the only thing we can say.
Bruce Nadeau from SunTrust. One definitional question on the protocol. Is the rule out for all bicuspids inclusive acquired bicuspids or just congenital bicuspids because the prior trials were all really congenital bicuspids for the rule out, I think.
It's hard to distinguish whether bicuspid valve is congenital or acquired. Acquired means actually fusion of the leaflets, and those are actually considered tricuspid valves because you see you can clearly see and as I'm sure, I can tell you that you can clearly see 3 leaflets and 3 commissures. So the congenital ones that we identify are mostly, let's say, CT scans, the congenital ones. I mean like we would like to get 100% through by customer trials.
And then my second follow-up is on you brought up the EOA as being an important success factor. You spoke to the coronary access, but there's also when dealing with long term implants, pacemaker rates, ability to expand in the face of heavy calcification and maybe lethal thrombosis where you may in fact have an advantage. Could you just comment on those three other elements?
Yes. So to start with the last one, I think the lethal thrombosis, of course, it is very speculative, what I say, but we think that better hemodynamics, the superannular performance of our valve, that you get better washing effect of the leaflets and that valve leaflet thrombosis might be lower with our platform. So that's the only thing. So when you talk about face masking, of course, that is something where we have a close look at. We see still a wide range of face masking implantation.
We see centers that have a face masking implantation rate as low as the surgery, and we see that it has higher. So currently, we're doing also some studies to understand better what is now the predictor for conduction disturbance. And when we know that once we know that better, we hope we can drive that down further. Completely agree with you that the lower, the better it is. But we see already low rates in the 5%, 6%, 7% in some centers.
So we Expensive force. Yes, so the expense of force. So we think that with the self expandable valves, you have enough radial strength to really treat bicuspid patients. So it's not that we have 0 experience. Actually in Europe, a lot of patients with bicuspid valves are currently treated.
And it's, of course, different in the environment in the United States where you have to get FDA approval to get an indication for it. But in Europe, lots of patients with bicuspidata are successfully treated.
Thanks. Josh Jennings from Cowen. I was just hoping to follow-up on Rick's question earlier just about the small annulus population. I mean, one, can you size it up for us in terms of the percentage of small illness patients that get surgical valves or open surgery historically? And then is that where you're really seeing the share gains take place is in that segment?
Yes. So again, of course, and I would love to answer your question directly. How many patients were at a low risk population with a small size? I cannot tell you at this moment what that percentage actually is. But of course, there are lots of patients it depends on the population we're looking at, but roughly, it will be about onethree of the patients that have a small size.
But with the low risk data presentation, look at those 21s and the 2023, etcetera. But about
high risk, intermediate risk, a little over onethree. Yes.
Great. And then just
Yes. So I would say 2 things there. So Mike is absolutely right. So we have seen significant share gains as physicians, whether they are strong electronic users or they use competitive belts, really understanding the benefits of the hemodynamics in those small annulus patients. So even physicians who historically have not been strong core valve users, as this data continues to come out have moved their small annulus patients to CorVel.
As they are getting more experience with that, they're seeing the benefits of those hemodynamics. We're now seeing that beyond just those small annulus patients. And then to Mike's point, as we skirt the 34 and we start to see some of the improved performance there, we're relatively optimistic that we'll see that as well. So I think the telodynamic story, to your point, absolutely playing well from the small annulus, but it's sort of creeping across the rest of the continuum.
Great. And just a question on
the LORIS trial design. Can you just remind us, in terms of the decision not to include rehospitalizations versus the PARTNER 3 design? And then any thoughts, high level, on the LRT data that was just presented today, particularly the hospitalization rate?
Thanks a lot.
Yes, excellent point. Actually, across all our trials, we had mortality and stroke as endpoint. So we kept that also for the lowest patient population. What I really urge you to look at the repeat hospitalization also at ACC and the description around it because there are different repeat hospitalizations. What is exactly the definition and how to adjudicate repeat hospitalization is actually it's not easy.
So it's a much softer endpoint. You can have repeat hospitalization for all causes. You can say, well, we just focus on repeat hospitalization for health reasons or you can say for heart failure or you can say repeat hospitalization. So there are many different definitions. So I think that makes it hard to compare if you have repeat hospitalization in your endpoint to compare one study versus another one.
And so therefore, we focus really on mortality and stroke, which matters, of course, very much for patients. They want to stay alive and they want to stay happy. And so that's across all our trials. And so then therefore, we choose that. Of course, we have also secondary endpoints, so we also report other endpoints as well, including repeat hospitalization.
But please take attention to how it is defined because that will be different. Ron's data. So actually, I think it gives us a good feeling with the data that he presented. I think, of course, our trial is much larger sample size, so I think it's more robust. It's mostly SAPIEN data that he presented, But I think it's heading in the right direction, yes.
It's a good outcome, I think. It points to the fact that it's really a good alternative, what he presented compared to Surfin.
Robbie? Robbie Marquez, JPMorgan. Two questions, maybe one TAVR, one TMVR. With TAVR, you have some new types of self expanding valves coming out in Europe and moving into the U. S.
And some new competitors coming in. Can you give us your thoughts on, A, how you feel you're positioned versus those competitors? And then, B, what you can do to hopefully maintain and prevent loss of share?
So I think we're going to remain focused on the story that we've been telling and the data that we've been generating around this whole, again, this whole hemodynamic story and the benefits that the ProValve has. We're seeing competitors into the market. We are not yet seeing a lot of traction in Europe. So we'll continue to watch that. We're expecting the same kind of entry into the U.
S. I think depositions are going to evaluate these on valve performance. And when I look at the performance of the Pro valve right now, we're feeling very, very confident about that. So of course, we'll continue to watch it, but we're feeling good about where we are in the story that we're continuing to tell.
Do you think pricing is going to come down in the U. S. Or Europe with new entrants?
I think if we look at any market, the more untrans you get, right, we'll see some pricing pressure. This has been a pretty price stable market. It's been a pretty price disciplined market. I think we'll look to maintain that as much as we can, and we'll continue to watch and see what our competitors do.
And then on TMVR and the Intrepid program and your repair program. Intrepid, can you remind us where you stand in terms of getting transfemoral access, how far out that is? And is it a reality? And then on the repair side, some of your competitors are going different flavors of repair. Can you give us any sense of which type of repair device you're going at and are you going after multiple options?
Yes. So on the Intrepid side, remind me of your question again, the first one.
Where you stand in terms of transdermal access? Yes.
So our belief is that in order to be successful, we're going to have a transdermal or transhepral system. So we have set our focus very specifically on the ability to develop a transdermal system. So, I think we've got really good line of sight to that now. We've got a strong engineering team working on that. So, we will our goal is absolutely to come to market with a transthermal system.
And then, repair. So, I'm not going to talk a lot about repairs, because as I said, we're feeling really good about what we have right now. We're really focusing again on things like ease of use and lifetime management of our repair technology. It's moving I think it's moving at a good speed. So we're comfortable with that.
I think that this is early times in this whole market, and I think we're seeing a lot of things coming. We're seeing some things fail very early, As you would expect, we'll see some things come a little further and potentially fail. I think this is a market we're just going to watch really closely.
I'll just add just to maybe help Nina's comments, but part of the reason why we're being so vague and not sharing more on the repairs because we do have approach that's different than some of the other approaches you've seen out there. And so we want to keep it as close to the vest as possible for as long as possible.
Thank you. Jason Mills, Canaccord Genuity. Thank you for doing this meeting. On the Mitro side, Nina, first, I appreciate at this point, it seems silly to try to ascertain whether or not enrollment is accelerating or accelerating. What we have heard though is it's very, very hard to enroll that surgical, both your trial and others.
Maybe talk about that, whether that's true and what you're seeing and maybe what that does to inform how you'll design trials in the future as it relates to mitral. The FDA and I know they're holding town halls today and other days on structural heart and they continue to do that. You think it's possible we're going to see for replacement devices getting away from this randomization to surgery? I mean, it's not done that much. And I'm wondering what your thoughts are on that.
And I'll ask Eric Bang in the back to come. He's the Director of our clinical program. This is it's a slow enrolling trial. We expected it to be a slow enrolling trial. It's again, early, early days.
We saw COAPT and various slow enrolling trial. I'm pleased that we're enrolling faster than that, which is good. We continue to have discussions with FDA about the design of the trial to see whether or not there are any protocol adjustments that we might want to make. We may make some small protocol adjustments as we go forward, but we'll be able to disclose that I think after we continue to have FDA discussions. I don't know, Eric, if there's anything you want to add?
Yes. And so as we work with FDA on the current APOLLO trial or as we look at alternatives, certainly, FDA is open to the designs of the control arms primarily because there is not a standard of care for these patients. And so as we see it today, we still have an option forward with their current trial design, but we're definitely going to continue to explore opportunities moving forward.
So just as a follow-up to that, on the mitral side, appreciate that you don't want to disclose too much about your internal programs. Will over the next 3 years your mitral program be developed both via internal programs and M and A in your view? Is that a fairly high probability sort of going both ways?
I would say yes.
Matt Miksic from Credit Suisse.
I had a couple
of follow ups. 1, just on expectations, Doctor, if you could, on the when we see the inflection or when we see the sort of uptake, what this looks like in the community, assuming that we get positive data in a couple of weeks and assuming that approval comes for both valves by the end of the year or something like that? I mean, help us understand maybe that process and maybe what how it might be different from the process around intermediate risk? And I have one follow-up.
Yes. So I think with the low risk, what's I think is also will also be important to look at the baseline characteristics, what is the age of the population. And I think when you when we show that low risk is non inferior, suppose that it's non inferior to surgery, what is then the reason to do surgical AVR in certain type of patients? I think when we have proven this, the only question that remains is the durability and where people may be a little bit concerned about, have you proven it? On the other hand, surgical data is also limited on durability.
And we have always claimed that we had a 13, 14, 15 year follow-up, but it's not based on echo data. It's based on reoperation free data. So everybody currently understands that actually there's a shortcoming in the surgical literature. So I think that points to the fact that durability might be an issue, might be a concern, but actually, it's maybe we just have to wait for a longer follow-up. The good thing is about NOTION, the NOTION trial, 7 year follow-up actually showed that TAVR had a better durability than surgical ADR.
So that takes away a lot of the concerns that people currently have on the durability of transcatheter heart valves. So we have a long term follow-up now already, and there will be patient up to 10 year follow-up for both of them.
Just to push on the inflection, I mean, does this take 6 months in the community? Does it take some what is middle of next calendar year, I mean, early next calendar year, when would you expect kind of an uptick?
Yes. So of course, everybody will be aware, I guess, after the AC presentation what the results are. And so people are already anticipating what am I going to do once we get approval. And I think the uptake might be pretty fast after that. I think also that patients will ask for it.
Patients will hear this as well. I mean, there might be COVID-nineteen in the New York Times. And so maybe those trials will also be published in I don't know, but the ejurmis may pick it up. And so the clinical the patient will pick it up and will go to their physician and say, can I not have a chest cavity aortic valve instead of surgery?
I think we're seeing that shared decision making is going to become a bigger issue and low risk assuming again that the trials are positive. Once patients start to realize that there are options, and although physicians hate when we say this, right, a patient walks in and says, I don't have my chest cracked open, I know that there's another alternative. And so physicians are telling us that they are anticipating longer discussions and patients really coming in with requests for TAVR versus surgery. And so they're going to have to take that into account.
And what I also so I'm also Chief Medical Officer for Cardiac Surgery. And so what I'd say was to the surgeons that we have the discussion now is that we should focus on those patients that still need a surgical aortic valve replacement. That means those with extensive coronary disease, where you need a coronary bypass operation at the same time, those patients with double or triple valves and those patients that also need a replacement of the ascending aorta. And that is a little bit more difficult type of operation, but we need those surgeons. So I think as surgeons, we should focus on those type of patients and how to educate the next generation of surgeons.
There will still be plenty of surgery that is needed. And there will be patients, for example, with a transcatheter aortic valve that develop endocarditis. It's the same rate as with surgical endocarditis, but the option is not replacing the transcript. You have to take it out. And so there will still be surgeons are still needed for the future.
Mike, Venezuela?
Yes. I would just say, for those that were for this, I was in the room for Waxman's presentation. And you heard one of the questions from the panel, just okay, this is great, you're showing us 30 day in 1 year data, but we're talking about patients that are going to live 10 to hopefully 20 years. So
what we're
going to see at ACC is going to be 1 year into your projected data, right? And so it's still for surgeons, it still doesn't answer that question. And because if we go into this dynamic where patients are asking, well, I don't want to have surgery, I saw the I read the USA Today article and I saw it on Good Morning America, and I don't want to have to crack my chest anymore. Then the conversation we don't have 10 year follow ups on these valves. So which valve do I feel most comfortable putting in a patient that I believe is going to last for 10 plus years?
And so maybe and so that's part of what our messaging has been, particularly post the papers that came out last summer. I know that's going to be covered in the symposium tonight. That's a Medtronic sponsored symposium part of it. There's a Doctor. Herman has a session, I think at 3:30 today on mismatch.
But maybe just spend a minute, Peter, on just coming back to say, why when valves fail, why do they fail? And so I think educating people on that because ultimately if we're talking about patients asking for TAVR and physicians making decisions based on which valve they are comfortable is going to still be working a decade out. So the question of why might A valve fail is an important one.
Yes. So good points because when I discussed the face prosthesis mismatch issue, I pointed out to mortality. But in surgical literature, we also have shown that if you have patient's mismatch, that also has an impact on durability. So the better your hemodynamic performance of your valve is, the longer it will last as well. So those are important factors to take into account.
So why would a heart valve fail at a certain moment? It will mostly calcify or you may get an infection. Infection is something you almost cannot prevent. We always tell patients, you have to go to your dentist, you have to be careful with your valve. If you get a wound, it should be cleaned, etcetera, those kind of things to lower the infection rate and lower endocarditis rate.
But if the valve calcifies, that's something you can hardly prevent. The only thing is when we think that if you have a valve that opens semantically, so if you have the forces are distributed on all three leaflets equally, the valve will last longer. And that's something we have mimic in our laboratory in Orange County, where we put the valves in. And if you have the valve that is not completely circular at the base where you implant it, it's still circular at the level where the valve leave its function. That is because of the superannular design.
And then your 3 leaves its open somatically, and the stress on the leaflet is less than if just one leaf that gets a lot of blood instead of the other all three at the same time.
Yes. Just
follow-up, if that's okay, on the NCD. Just your thoughts, business planning on expectations for the NCD
and 3 months. That's my knowledge. We'll see the NCD at the end of this month. I think 27th is the date that has been talked about. I believe that we will see volume requirements less than what the societies initially proposed, slightly more than what we currently have.
We've been aligned with the society that at this point, we still need some volume requirements until there's an outcome that we can tie this to. And so I think it's going to be in line with everything we've been saying since the start of the NCD process.
Bruce?
One of the funny things that happened on Saturday is they showed the relationship between SAVR outcomes and volume, and they were indistinguishable from the TAVR outcomes in volume. So it made the whole MCAP seem a little ridiculous. I wonder if you'd comment on that. And also secondarily on, let's say, both trials when you combine them at ACC show just strong trends on hard outcomes. What does that mean for the SAVR patients over 65?
Will doctors have to tell them that TAVR is a very legitimate alternative?
I think to start with a last point, yes. I think if it's a heart endpoint like mortality, which is different, I think doctors have to tell that if they are honest with their patients, the patient will ask, so what is the benefit then of surgery? I think for a surgeon, it's hard to explain at that moment what is then the benefit. So I think, yes, rightfully so, they have to tell it. And your first point Yes, right, exactly.
Yes, sure. Well, suppose that there will be a 3% or 4% difference in mortality. I mean, then you maybe that's hard, of course. But yes, you're rightfully so.
You're talking to the surgeons. Yes, you're right.
You're right, surgeons. So it's hard for me to express myself, but it's you're absolutely right. Yes?
Just one more question for me. This morning, Doctor. Kathain, we saw your friends in Rotterdam. Assume they're your friends. Yes, yes, sure.
Do a live procedure and using the SENTINEL device and they were stressing the importance of protection. They showed us the clots and there are several docs on the panel that basically said one said, I do every single case with protection. Another said, no way because it's so expensive. What are your evolving thoughts about the importance of this? How would you how should we think about it?
Gosh, it sounds important, and yes, stroke rates are low,
and what the future holds? I think you just hit the conundrum right on the head, right? So the stroke rates have been very, very low and so physicians will point to that. There's a, I think, an emotional reaction with that device when you see debris that's pulled, right? So the data was negative, as you all know.
It's hard to believe that somebody is going to do a stroke outcomes trial because they're so big and they take so long. But even our neurologists, as we have a strong program at Medtronic, and I talked to our neurologists about this. And they will say, we want to see data, but it's hard to argue with that going taking that from the brain, not having a go to the brain, that has to be a good thing. There's still we're not sure if you see just a little bit of damage with that device. I think that the jury is still out on that.
And so I think overall, what physicians have been telling us is intuitively, you want to do everything you can to protect the patient from stroke. One stroke is if the stroke too many, They don't see a lot. Their feeling is that the Sentinel is expensive. Boston will figure that out. But from an overall embolic protection, I think we're going to see growth in that.
I do. I think we Well, a stroke is devastating when you're 90. I don't want to put quality of life on people's ages, but a stroke of 65 or 75 could potentially be considered more devastating. So, there may be opportunity
there. Kristen Stewart from Barclays. I was just wondering if you could maybe just share your thoughts on the total size of the mitral opportunity bulk repair replacement. I was struck that your market estimates of $4,000,000,000 by FY 'twenty seven weren't very different from what you guys had talked about this past summer despite the CO OP trial results. So just trying to think about how you guys still view the split between replacement and repair?
Because it seems like some other people are rethinking, it sounds like you might be too, what repair might be as a percentage?
I don't think we really know yet. I think it's a market that we continue to watch and to size. So we're showing you what we're looking at right now. We're continuing to watch MitroClip. There's no approval yet.
There's no reimbursement yet. And so I don't think we really know what's going to happen there. So we'll watch that carefully, and we'll continue to size if we think that a change is warranted.
I think the beauty of confidence was that it shows that reduction of MRI works. You have a better survival. And you could say with a repair device, you will reduce MR but not completely eliminate it. And maybe with a replacement, if you completely eliminate MR, maybe you get a better survival. But that's all so therefore, Molina said, we don't know actually which market and how big it will be.
And with degenerative mitral regurgitation, so far, it has always been repair as a preferred approach. So but maybe replacement has also worked out very well. Still a lot to learn. And then
what's been the main challenge in terms of moving the Intrepid device trans septal? Because you guys had thought about getting it in some sort of program by the back half of fiscal 'nineteen. I didn't I don't think I heard from you today a specific time line for that. So what's been the main challenge? Is it just you could do it, but you're trying to size it much
smaller or So I think we're looking at 2 things. We're looking at making it transheptal and we're looking at making the system smaller and we're looking to do that together. I don't know that a 43 transcep system is going to be very helpful to the market. And so we're looking to do both of those things at the same time. And there are engineering challenges that get raised when you do that.
I think we're working through them. And I think the team is feeling pretty good about their ability to get there. Deer? For first in human? Yes.
Say within the next 12 to 18 months. Okay. Thank you.
One more question here
before we wrap up, Adam.
Adamator, Wells Fargo. Thanks for taking the question. I just I wanted to follow-up on the NCD commentary. Any sense for how much greater you think the TAVR requirements will be versus the current NCD? And just any thoughts on how that will impact TAVR volumes?
In terms of the volumes that will be required in the NCD?
Correct.
Everything that we're hearing is that it will be less than the 50 that the societies originally proposed, a little bit more than we currently have now. So I'm guessing somewhere in that mid-20s range, but it's conjecture on my part, we'll have to wait for the 27 to see what that looks like.