All right, everybody, thank you very much for joining us tonight. It's an exciting evening for Edwards, and glad you could be here to enjoy it with us. Just real quick, I want to call attention to the forward-looking statement. If you could just spend a second reviewing that, some important information here that we'll adhere to as we go through the presentation this evening. In terms of the format of tonight's event, we're going to spend about a half hour with the team you see here on stage, and then we'll transition to the TMTT portion of the presentation. As a reminder, tonight's event is being recorded, and a replay will be available after the conclusion of the event. Again, thank you all for joining us. Really appreciate it. With that, I'm going to turn it over to our CEO, Bernard Zovighian.
Yes, you know, good evening, you know, everyone, and thanks, you know, for being here. It has been an exciting day, you know, for the company today, and maybe, you know, more, you know, most importantly, for all of the patients we serve. What you have seen, you know, between yesterday and today is, in my mind, you know, the result of our very unique innovation strategy, where you know us, you know, very well. You know, what we want to bring all the time is highly differentiated technologies, our commitment to innovation and evidence in everything we do. You know, TAVR, mitral, tricuspid, and soon, you know, AR and heart failure. You know, like we have said in the past many times, it takes time to build, you know, strong category leadership, you know, like this.
And in my mind, in our mind, you know, today is an inflection point, you know, for the company. You know, for TAVR, you know, for EVOQUE yesterday, I'm sure you have seen the data, and for mitral replacement and M3 today. So, like, you know, Mack said, for the first part of this session, we are going to focus on PARTNER 3, seven years, you know, this amazing, you know, data set that you have seen today. I'm very proud of the data. We are very proud of the data, and very proud about the many physician partners that have been part of this TAVR journey, and the teams, you know, the Edwards team, who have made, you know, this, you know, possible. We are joined by two physician partners. We need, you know, very little introduction, Dr. Martin Leon and Dr. Mike Mack.
I'm going to start with Dr. Martin Leon, Professor of Medicine at Columbia University, Director of Cardiology at New York-Presbyterian. Also joining me on stage is Dr. Mike Mack, Medical Director of Cardiac Surgery at Baylor Scott & White Health. Both have played a major role in advancing structural heart innovation. Obviously, you know, they're highly, highly published, they're respected globally. But also, you know, I know that, you know, they care a lot about this. Millions of patients around the world were able to get access to treatment because of their leadership over the last 20 years. So also with me on stage tonight is Dan Lippis, our leader of TAVR. Dan joined, you know, the Edwards TAVR team about 15 years ago. So he has seen every step of a SAPIEN journey.
So I'm going now, you know, to turn it to Martin and Mike for a quick overview of the data, and then, you know, obviously, you know, opening up, you know, for, you know, questions. Mike, you want to start first or Martin?
I think everybody heard from me earlier today, so why don't we start with Martin?
Sure. I think today's been an exciting day. I've been involved in this journey since the, you know, first development of the first TAVR in the late 1990s, and have worked very closely with Edwards since 2004, and the beginning of the partner trial in 2007. So it's an 18-year journey. It's over 10,000 patients, and it's a series of clinical trials that have netted more than 200 publications, and I think have helped us to establish the field and really to pave it with the kind of clinical evidence that makes people feel confident that we've developed a therapy that is a meaningful contribution for the management of patients with aortic stenosis. Not to the exclusion of surgery, but incorporating with a surgical platform how we can best manage all patients.
But I must tell you, even in this period of de-escalating randomized trials and publishing a lot of manuscripts in New England Journal of Medicine and whatnot, everybody had always said, well, the early results are nice, but what about durability? What about the late results? And almost as if there was an expectation that something would fall apart suddenly after a period of time, and all of the good faith and goodwill and trust and success that we've achieved would suddenly be dissipated with later results. So today is the first time that I would say that we really are beginning to show late results. Beyond five years to me means late results.
This is the beginning of the vulnerability window where you're seeing some of the early failures with surgical aortic valves that have not done so well begin to express themselves by five, six, seven years, certainly by 10 years. So if there's going to be something that suggests that other than the more orderly structural valve deterioration that happens to every bioprosthetic valve over a long period of time, accelerated valve failure, we should begin to see signals of that. That's why the seven-year trial is so important. But I will tell you that doing long-term follow-up studies is not so easy. And we're learning that, and I think that it's one of the reasons in great deference and respect to my surgical colleagues, that the clinical endpoints that have been used to really define durability for surgical valves have been fairly simplistic.
It's basically a head count, are you alive or dead, or have you needed a re-intervention? And the data is relatively incomplete, so it's a little bit hard to look for predicate parallels in the surgical literature. But the PARTNER 3 trial is a younger, lower-risk population. Mean age is 73-74. So we had the expectation that we might be able to look out to 10 years and get some real insights into durability. We published the data at one year, two years, five years, and now today we have a manuscript in the New England Journal of Medicine at seven years. And I sat next to Jane Leopold, the senior editor of NEJM, as Mike was presenting the data.
It really gives us a sense of both pride, comfort, and excitement that we've been able to demonstrate with a very careful analysis of the data that this device does sustain clinical endpoints out to as long as seven years with results that appear to be similar to, not inferior to, comparable to what you'd see with the best surgical valves. That we're seeing that re-intervention rates are almost identical to what we've seen with the surgical randomized cohort. That this index of bioprosthetic valve failure that we laboriously defined in a VARC-3 document, including careful echocardiographic assessments, showed again stability of the improvement over the course of seven years with results that were almost identical to what we saw in the surgical valve.
With careful analysis of looking at mortality and other indices by a variety of statistical techniques, we feel very confident in saying that the two therapies are very similar out to seven years. There was a subtle attenuation in the difference over the course of between one and seven years, but still the point estimates are almost identical at seven years. An index that we look at that really speaks to the totality of benefit in long-term follow-up studies over a period of time, something called a restricted mean survival time, suggested that there was at least equivalence and maybe even a slight benefit accruing to TAVR versus surgery, at least over the first seven years. We come away feeling confident, not cocky, but confident. The results are as we had expected.
There was no reason to imagine that there would be some change in the valve later on that would speak of significant premature failure, and we think that the data that we currently see certainly reaffirms that. In addition, later tonight, we suddenly got very, very aggressive and decided that we wanted to show all the data as quickly as we can and to be extremely transparent. For the first time, we're going to be showing randomized data in over 4,000 patients at either seven and 10 years, 3,000 patients with intermediate risk categories. Now, that's even more difficult because they're older to start with, so at 10 years, the mean age of these patients is over 90 years, so you can imagine that it's very difficult to get that kind of long-term data.
But we're going to show you two studies that were done out to 10 years and really expose those results for the first time, which again, to us, reasserts the confidence that TAVR is a durable procedure out to 10 years, comparable to surgery from the standpoint of durability, with early benefits accruing to, again, the less invasive nature of this procedure that should give us confidence in terms of being able to inform patients and to inform the public and referring doctors that this is not just a convenient, easy-to-perform therapy that is generalizable now in almost 900 cath labs and hospitals in the country, but one that is durable as well.
Thank you, Martin, for this very comprehensive and putting everything into perspective here. So now, you know, let's open for, you know, Q&A.
So, Travis Steed, Bank of America, maybe just high level, you still recently have seen the surgeon community, you know, say we're doing too much TAVR in low-risk patients. Is this the data? Do you think this is definitive evidence now where you can say TAVR is durable and you can start to see more referrals come in the low-risk population?
We should have a surgeon answer that question.
Yeah. What I would say is the following. First of all, as Martin said, previously, we didn't have systematic follow-up of surgical valves because there's no reason to. It was the only therapy. But now, for the first time, we do have systematic follow-up of surgery and TAVR. And we know what the durability of surgical valves are now for the first time. I think the bottom line of all this today is reassurance. Reassurance that the performance of both biologic valves in both surgical and TAVR are great at seven years. Now, I don't think this is practice changing. I think it's reassurance that practice will stay the same as it is, you know, which is an 80/20, 85/15 TAVR versus surgery.
But it gives you confidence that if a patient isn't optimal for TAVR, bicuspid valves, non-transfemoral access, concomitant coronary artery disease, that surgery is a great option. You know, I think it's the basic rule of thumb that when you have two therapies and one therapy is less invasive than another, it's like baseball. Tie goes to the runner. A tie goes to the least invasive therapy. So all the less invasive therapy, and this is TAVR, has to do is tie in order to win. I don't think that this should justify continuing going down into younger populations because, you know, this is data just on the population study, and there was only a few percent patients under 65 years old. We know from surgical experience that biologic valves tend to have more structural valve deterioration the younger that you get.
So that was going to have to be a group that studied no matter, you know, it's the bioprosthetic valve independent of the route by which it's delivered. Thank you.
Thanks, Mack.
Thanks. Robbie Marcus, JP Morgan. Congrats on the positive trial today. Question for me. In the appendix, it showed the data. The headline data was very good and comparable and statistically not significantly different on the main trial at seven years. There did appear to be some worsening trends on cardiovascular mortality and disabling stroke and mortality as you moved into years five through seven. So I was wondering how you're thinking about that. Are the numbers substantial enough to make any kind of decisions off of that? Because they did hit in the landmark analysis statistical significance. So just getting your thoughts there and how that might impact or not impact practice. Thanks.
So I think there's no question that there's catch-up between years one and seven. I mean, TAVR clearly outperformed the first year. There is some catch-up of surgery either doing the same or slightly better, including with death from years one to seven. But that's why the restricted mean survival time is important because it does show that the events with surgery occur earlier, and you can go 134 days longer over seven years before you have a primary event. Now, the figure that you're referring to in the supplement is the landmark analysis of death. And the first part of that shows it without the vital status sweep. And I'll just take a second to explain that. So there's such a loss to follow-up as you saw. There was a disproportionate exit of patients on the surgical side that biased the outcomes.
The FDA mandated a vital status sweep. What that is, is that the clinical sites, not the sponsor, but the clinical sites are allowed to go to try to find those patients that had exited the study by a whole variety of resources at their hand, including LexisNexis, obituaries in the newspapers, things like that. They're able to find 13 more deaths in the surgery arm and three more deaths in the TAVR arm. When you look at that, that landmark significance went away. It still trended in favor of surgery, but it was no longer statistical significant. I think this is one of the major learnings of this, is that all trials should include this tool to be able to have completeness of follow-up because it does significantly impact what the findings of the trial are.
And it was interesting that that separation of mortality a little bit was both cardiovascular and non-cardiovascular deaths. And why there should be a difference in non-cardiovascular deaths is beyond me. Why there should be more cancers or respiratory disease? So there's a little bit of a play of chance here. And we're still talking about absolute differences that are in the 1%-2% range over seven years. So I don't think that that's either clinically or biologically important.
Yeah. I guess I'd say one other thing regarding long-term follow-up. You'll see the data being presented in the symposium to follow here that when you get into an intermediate risk population, that mean age was 81 when they entered the trial. By the time you're 10 years out, about 85% of the patients have died. So the competing risk of death overwhelms any potential benefit you're going to see to long-term follow-up. So it is one of the caveats that it's not like you snap your fingers and know how a valve's functioning at 10 years. It all depends on the population.
Thanks, Josh Jennings from TD Cowen. Wanted to just ask about SAPIEN 3 Ultra RESILIA, which is the current device commercialized, and SAPIEN 3 was studied in PARTNER 3. I mean, how is the clinical community going to translate these seven-year update data to SAPIEN 3 Ultra RESILIA? I mean, it seems that the hemodynamics may be a little bit better at the RESILIA anti-calcification action going on as well. But maybe just help us think through that. And should we be thinking that the impression will be that the current commercial device is actually better than SAPIEN 3? Thank you.
Yeah. It's certainly challenging because in med tech, things continue to change and they continue to improve, and how to factor what that level of improvement is going to impact in terms of clinical outcomes is always a little tricky. It's challenging. The RESILIA tissue, which has been available now on surgical valves for seven, eight years.
Exactly.
You know, now has a reasonable number of patients with follow-up that suggested several things, and even on the transcatheter platform, we have seen an improvement in the hemodynamics, especially in the smaller valves, so I think the improved hemodynamics, I think that the tissue difference and what's been seen in the surgery data suggests to us that there may be a further improvement in long-term structural valve deterioration. We'll obviously have to study that, but I think that it can only get better is what we're saying. How much better is a little bit difficult to imagine, but it can only get better.
We have already published seven years on the surgical side of RESILIA with the COMMENCE trial. We are going to continue following up with these patients.
Thank you, Joanne Wuensch from Citibank. Thank you for this presentation. I think some of the data points surprised many people and think some of them didn't. But I'm curious, what was your read when you saw the data being printed, published, pulled together? What were you like, "Yeah, I knew that"? And what were you like, "Oh, that's interesting"?
I mean, it's a good question. I think the first reaction was reassurance, you know, feeling confident. When we started this journey, as I said, 18 years ago, to imagine that we could take these valves and implant them in ultra-sick patients with very little understanding of what the optimal implantation technique was, what the imaging needed to be, and a whole variety of things, and that we could achieve this level of quality results with initial benefit and sustained equivalence to what has been more than a half-century of excellent surgery, I mean, I felt relieved. I felt reassured. Was there anything that surprised me? We look at the data very carefully. And whenever you slice and dice data, you're always going to find something. So we did find some things that were kind of interesting. And I'm, you know, and we're still trying to sort it out.
And there are going to be many, many sub-studies. That's what we do. We publish manuscripts. We do sub-analyses. So we'll try to see if we can point out some of those things. But I will say that we certainly learned some things that I think are meaningful that we'll have to continue to look at. And it's a little bit of a tale that in the first year, there's no question that these less invasive transcatheter valves perform better than open surgery from the standpoint of clinical outcomes. And from the standpoint of, as Mike said, it's not even a tie. It's superiority. That superiority difference tends to narrow over time. The point estimates are very close now at seven years. They're flattening out.
To a certain extent, and this is perhaps a bit whimsical, but I call it kind of the patient vulnerability hypothesis, which is you've got patients, and these are somewhat older patients. They have many comorbidities. They're vulnerable to any major procedure in the setting of severe symptomatic aortic stenosis. With open surgery, they're more at risk to having serious early events. They can't tolerate open surgery. So the ones that can't tolerate it expressed themselves early, and that accounted for the difference. But, you know, that said, this is a randomized trial. Those same vulnerabilities are in the TAVR arm that begins to express itself a little bit later. So we see a little bit of a catch-up over time so the two become much closer. So that's one of the things that I think we're observing, which I think is an interesting observation.
We did see some interesting late events. We saw an increase in early spontaneous myocardial infarctions in the surgery arm, and then between five and seven years, we saw a clustering of events in the TAVR arm. We scratched our heads, didn't quite know what that meant. These were not major MIs. These were patients that ended up having angioplasty and stents, and so they were not life-threatening, but it was something that we didn't quite expect, and we wondered that the surgeons, when they do the operation in patients with concomitant coronary disease, they often do bypass surgery as well. We tended to shy away from that, and we didn't do as much angioplasty in those patients with coronary disease. Maybe that difference in the concomitant procedures expressed itself a little bit later during the course of follow-up.
So that was one of the interesting observations that I think was something that we'll have to explore further. I think the echocardiography was also important to us. First time that we've had randomized echoes to look at seven years by a core lab. And, you know, the core lab is pretty blinded. They don't know what devices are being implanted. And I have to say that was extremely reassuring that we weren't seeing evidence of either structural valve deterioration or bioprosthetic valve failure that would indicate that there was a change. The expected rate of increase in structural valve deterioration that occurs with every bioprosthetic valve began to occur with both surgery and with TAVR between five and seven years. The frequency of SVD and BVF doubled during that period of time. Still very, very low in the range of 5%.
We're seeing what we expected to see. We see some subtle things that are interesting to continue to observe. The message to referring doctors, to patients, is going to be one of confidence and reassurance.
And for me, you know, and for us, you know, as a company, you know, what we know is that most valves, you know, mostly surgical valves, when they fail, you know, they fail between five and seven years. And we have seen many of competitor valves, you know, failing between five and seven. So for sure, you know, I was looking at this study with a lot of interest. And knowing that, you know, the vast majority of the surgical valves are also Edwards valves in this study. And so to see this kind of outcome with, you know, basically, you know, Edwards technology on both arms is also, you know, very reassuring about, you know, what we do for a living as a company.
We've got about five more minutes in this portion of the session. So maybe just sneak in two questions. First, Marie, and then Larry.
Marie Thibault, BTIG. As we think about this data, how does it sort of play into potential developments with the NCD and who needs to be part of workflow? Is this data that CMS is looking at? Is this something that you make available? Just any comments, probably for Bernard and Dan.
Yeah. You know, maybe it's a question we can tackle on Thursday. You all know that on Thursday, you know, we have earnings, and we can talk about, you know, NCD at this time. You know, how about we use this time with the physicians to make sure you have all of your clinical question answers, if it is okay with you?
Thanks. Larry Biegelsen from Wells Fargo, congratulations on the data. Just a question on, so the FDA posted the six-year interim data, as you probably know. It got some attention in the medical and investment community. You're not going to be presenting, you know, until the 10-year data is available. Do you know if FDA is going to keep posting seven-year, eight-year, nine-year data on the post-approval study site? And if so, how are you going to address that? It's partial data, you know, but people are still looking at it. Dr. Leon, did you understand my question?
Yeah. It's a little bit of a, I don't want to say it's a dilemma, but it's, you know, I can understand how it might create some confusion.
When the eight-year comes out, people are going to look at it, but it might not be complete.
It won't be complete because there are not going to be any eight-year echoes or nine-year echoes. There'll be echoes at 10 years. Really what we're talking about is durability. Durability is going to require that kind of imaging study to make those comparisons. The only thing you're going to have is you're going to have a partial reading of the reintervention rates, and you're going to have some of the data on overall mortality. That's the extent to which you're going to see very much during the eight and nine-year periods.
So you would, this audience, you would recommend to basically take it with a grain of salt? Like how, because a lot of people here are going to be looking closely at that data.
I think we'll all look at it. The FDA is going to look at it. You know, if there's something that's strikingly different that we need to explain, then we certainly will look at it more closely. But unless there's something that suggests an unexpected finding, you know, I think it's going to be very incomplete. It's not going to be adjudicated in ways that we would normally do it. We're not going to publish it. It's going to be on an FDA website.
Just to complement, you know, this conversation here is, like Martin said, you know, right after this event, we are going to show, you know, the PARTNER 2 10 years. You are going to see some 10-year data in about a few minutes from now.
In 3,000 patients, so.
All right. So we're right about at the halfway mark. So with that, maybe, Bernard, I'll turn it back to you. I know you wanted to close out this portion of the session, and then we'll ask the TMTT panel to come up afterwards.
No, thank you. You know, great conversation, you know, great questions. You know, so let me try to wrap up, you know, what we heard, you know, today, and what we heard, you know, today, you know, during this conversation, but also during Dr. Mike Mack, you know, presentation. I want to start with what we knew before today. We knew that, you know, the SAPIEN platform was, you know, the most studied valve. More than 15 years of trials, thousands of patients, 12 New England Journal of Medicine publications, more than 1.2 million patients treated globally with this platform, and we know what's happening every day. You know, we get the feedback, you know, from physicians, you know, globally. We know that what we knew before today was that TAVR at one year with SAPIEN for low-risk patients in the PARTNER 3 study was superior to SAVR.
This is what we knew today, before today. What we learned today is that the excellent performance of TAVR is now proven at seven years in terms of durability and valve performance. And this impressive valve performance and durability is further supported by what you are going to see, you know, with the 10-year data. It is also great news, you know, for patients where physicians and the heart team, and we like, you know, very much, you know, the heart team concept, we have options between a great SAVR option or a great TAVR option. So in our mind, you know, it is a great day today with a lot of confidence.
What you can expect, you know, from us is we are going to continue to partner with world-class physicians, with societies, with regulators, with payers to innovate and ensure that any patients who deserve a treatment, it could be a symptomatic patient, it could be an asymptomatic patient, it could be a patient on a waitlist today, and there are many, you know, there are many global patients like that, they will have access to a great option, SAVR or TAVR, and after, you know, what's, you know, probably, you know, the more exciting, you know, to me and to all of us at Edwards is after, you know, 15 years of leadership, there is still a lot to come. There is, we are still, you know, super excited about it. You know, we are going to bring, you know, more, you know, more innovation, more evidence, more partnerships.
It is an exciting field, you know, 15 years, you know, later. I want to thank both Dr. Leon and Dr. Mack, you know, for their dedication to advancing this field the way they did it. It is unprecedented. They have been pioneers in having the vision that TAVR could be an alternative to SAVR 20 years ago. Today, everybody gets it. 20 years ago, you know, they were, you know, the pioneers. Again, you know, Mike and Martin, you know, you led, you know, 20 years of unprecedented world-class evidence impacting millions of patients. And we all thank you for that. Thank you. We are now going to transition to the TMTT session. Martin and Mike, thank you so much. Dan, thank you. Let's transition to the TMTT section now.
And also the exciting, very exciting data we have seen over the last two days, EVOQUE yesterday, and M3 today. We are joined with Dr. David Daniels and Rahul Sharma. Dr. Daniels is the section chief of Sutter Heart and Vascular Service Line. Rahul Sharma is the director of structural interventions at Stanford Health Care. We have Daveen Chopra, our Corporate Vice President for TMTT and surgical, and Dr. Ted Feldman who is the CMO for TMTT. So we are going to follow, you know, the same process. I'm going to turn over to David and Rahul to talk a little bit about, you know, what you have seen, you know, yesterday, yesterday and today. So maybe we can start with you, Rahul, about, you know, EVOQUE. And then we go to you, Dave, about, you know, M3, and then we will open up for Q&A.
Certainly. First of all, pleasure to be here. Thank you. I had the privilege of presenting the TVT Real World Registry, the outcomes in over 1,000 patients with the EVOQUE transcatheter tricuspid valve replacement yesterday across 82 sites in the United States. Most of you, if not all of you, will be familiar, of course, with the results from TRISCEND II demonstrating the safety and efficacy of the EVOQUE replacement system. And I think, you know, following the results from that study, following commercial approval, there was cautious optimism, I think it's fair to say. There was a little bit of hesitation around bleeding rates and pacemaker rates.
I think what the TVT registry data showed us was that even in an expanded practitioner population and certainly an expanded patient population, we confirmed the safety and efficacy and actually saw improvements in those two endpoints in terms of bleeding and pacemakers. And so the takeaway message for me, and I think for a lot of people was, you know, to use the word that was used in the last session, reassurance of the safety and efficacy of the device, including, I would argue, a higher risk population. We included patients with dialysis, which were obviously excluded from the original study. And for a number of reasons, we can get into, as I mentioned, mitigation of some of those risks of conduction disturbances as well as bleeding.
And I think, you know, the drastic improvement we saw in terms of reduction in tricuspid regurgitation was both acute and certainly sustained to 30 days, which in turn translated to significant clinical improvements whether you look at NYHA class or KCCQ. So I think optimistic. We have another device in the armamentarium with addition to edge-to-edge repair to build out the toolbox. Many more devices coming, but certainly this is a big step forward for patients who have tricuspid regurgitation, clearly no longer the forgotten valve. And so very excited for the near future and tricuspid valves.
Thank you so much. You know, maybe, you know, Dave.
Yeah. Thank you. Well, it's a pleasure to be here and honored to be here with all of you. I think today was honestly an unprecedented day and a really monumental day for therapy of the mitral valve. You know, the data that we had a privilege to be a part of demonstrated for the very first time a trial that achieved its primary endpoint in a fully percutaneous transseptal mitral valve replacement. The ENCIRCLE trial studied a population of patients who really had no other good options. These are patients who were very, very undertreated.
I think, you know, as we reflect and look back, you know, at the advent of TAVR, who extended therapy and allowed patients who had aortic stenosis who were undertreated and not able to be treated due to being high risk or otherwise unsuitable for surgery, at least initially, I think we're going to see that sort of a transition with TMVR, with the M3 valves specifically. The outcomes with respect to reduction in MR were really striking. We had essentially near elimination of significant MR in this patient population. That's not something we've been able to do in the transcatheter treatment of MR in the past, not to this degree. With that, we saw direct evidence of reverse remodeling or improvement in left ventricular dynamics as a result.
We also saw patients have a significant improvement in both the physician-assessed New York Heart Association heart failure classification or symptom classification, but maybe as importantly or more importantly, the patient's own self-assessed quality of life improved significantly. One of the two components of the primary endpoint, mortality, of course, is always very important, but our heart failure hospitalization as part of our primary endpoint was a really significant outcome. It was not just that they had to be admitted for heart failure. This was greater than 24 hours of admission. Patients had to get, in order to qualify for the primary endpoint, intravenous therapy or mechanical heart or mechanical therapies to improve their heart failure. These are outcomes that are very, very significant for our patients and for the healthcare system. So I think that's pretty much all I have to say about that.
Thank you so much, Dave. So let's open up for Q&A.
Thanks so much, Matt Miksic from Barclays. So just on EVOQUE and tricuspid, what are some of the most significant, and this I guess is for, you know, Dr. Sharma and for the team, is, you know, constraints to further roll out at this point? You know, how much is imaging a part of that challenge and imaging teams? And what over the intermediate and long term can be done to kind of simplify that, you know, execution of the interventionalist and the imaging team? Thanks.
For all, do you want to talk about your center maybe, and I can talk about it a little broadly.
Perfect. Yeah.
If that makes sense. Yeah.
So I think, you know, one of the things being involved from TRISCEND I to II and now commercial use is the appreciation of how pivotal imaging is to this, both in terms of screening these patients, but also intra-procedurally. I would say, like with any new technology, as we iterate ourselves procedurally, we start to understand better what we're looking at and how to judge, you know, how we deploy these valves and how to assess these valves. And so I think early on in our learning curve, we all struggle a little bit with the imaging in terms of imaging the valve, imaging the device. Fast forward to today where, you know, our procedure times are sub-30 minutes in terms of device times.
We're treating a more complex range of anatomies, some anatomies that were actually excluded from the initial studies that we're now treating commercially with great success, and so I think while imaging remains pivotal to this procedure still, it is by no means the barrier that it may once have been. There are cases, and I'm going to be careful here, that have been done successfully with intracardiac echo, where early in the piece, for a variety of reasons, where transesophageal echo could not be performed or at least not performed adequately to go ahead with the procedure in the trial, today in the commercial setting, we're able to either use intracardiac echo as an adjunctive imaging modality or indeed as a standalone imaging modality and complete the procedure successfully.
I think bottom line imaging is important, but it's by no means a barrier or a hurdle to expansion of the therapy.
I think what you see at Rahul's center is indicative that when you have a new therapy, you're always working on workflow and procedural kind of steps, and there's a continuous improvement. Rahul's talking about how it's improving at Stanford in terms of the imaging, but just the workflow of tricuspid patients being treated, right? That's something that when you first start a new therapy, it gets a little bit more convoluted, and then over time it smooths out, so I think for us, we at Edwards are both working on continuously to help open up new centers in the U.S. and throughout the world, help work through understanding their workflow, partnering with the team on ensuring that they get the best possible training for their imaging and the procedure, knowing that we're going to be there with them step by step as they continuously improve.
So I think that curve of improvement and opening up new centers is just continuing to undergo, and we hope to see the volumes continue to grow of patients being helped by this great technology.
Thanks. I wanted to ask about M3 in the ENCIRCLE trial. So two of the questions with this product have been ease of use and then applicability. We've seen very high screen out rates in some of the other mitral trials.
Yep.
Often that's because of LVOT obstruction issues. I noticed that was actually the minority of anatomical screen outs here. So can you speak to, is this a more broadly applicable device? And then usability, ease of use, procedure times did come down, but 4% of cases had to be aborted and there wasn't a valve implanted. So is this something that's going to be broadly usable across the physician universe?
Yep, so I'll start with the last one, so you know, in terms of the left ventricular outflow tract obstruction being a large, it's true. I think across the continuum of devices, that has been the biggest issue for transcatheter transmitral valve replacement. M3, 35% anatomic screen rate, I think is actually really low. The overall screen fail rate was higher, but in actuality, when we look through those specific patients, a lot of it was patients get consented and then treated with appropriate guideline-directed medical therapy. Oftentimes, their mitral regurgitation would improve. A pretty significant amount of that sort of screen fail was not really screen fail and was formally classified as such for the trial because they had been consented.
But it was what is already known in patients with secondary MR that oftentimes mitral regurgitation can improve with both medical therapy as well as cardiac resynchronization therapy. With respect to the question on usability and teachability, I would say that a few things have happened. Technology has evolved. The team at Edwards, the engineering team, is really the most impressive team I've ever worked with. We have had continuous evolution of this device from the very beginning. And I've been involved with this valve for a long time. Improvements in the dock with the hydrophilic sleeve, improvements in the performance of perivalvular leak with the PVL guard, and improvements in the valve technology.
And then I think, in addition to that, what we as a team and with the clinical specialist have added is proceduralizing the procedure and making it teachable, breaking it down into chunks that can be consumed. I think I said it in one of my sessions today. I still remember I proctored the first case at the Cleveland Clinic with Amar and Samir. It was 60 minutes. They had never done the case before. You know, they're quite good, but I think there's a lot of really good operators in this country. So as we've gone on and on and, you know, honestly, procedure times, you saw 77 minutes. We did a case the other day. It took 34 minutes. That's not uncommon.
I would say very confidently that the procedure time and complexity of the SAPIEN M3 implant is similar to M-TEER at this point as we start to gain, you know, more than a few cases, and that's going to expand and continue to improve as the device gets commercialized.
What you can expect, you know, from the TMTT team. I'm sure, you know, Daveen and Ted, you know, can talk about that. You know, it is, you know, what we have been doing in the last two years, you know, for EVOQUE. You can expect, you know, the same. You know, we are going to train physicians, support physicians, improve, you know, the procedure itself to make sure that it is going to be safe, very effective, easier to use, and to make sure we can scale, you know, basically, and having, you know, optimal patient outcome at the day, which is the goal at the end of the day.
Thank you, David Roman from Goldman Sachs. Dr. Sharma, yesterday in your presentation, you talked about the 56-millimeter valve only rolling into the trial later. I couldn't tell what you were trying to indicate with that. Maybe you could elaborate on your thoughts there a little bit. And then you just made the point about tricuspid valve no longer being the forgotten valve. I mean, that seems to be the case here with 82 sites and at least 1,000 procedures in the first year since approval. Maybe talk a little bit about the factors of what can make tricuspid valve treatment a little bit more mainstream and whether that's a referral channel question, a technology question, or something else we should consider.
So with regards to the sizing, the reason I mentioned that it was available later is because I wanted to provide context for the frequencies of each of the valve sizes. That graph that I showed, you know, the 42 and the 48 millimeter, sorry, 48 and 52 millimeter valves were the sort of most commonly used. The 56 was, you know, brought in a little bit later, but addressed one of the unmet needs, which was the larger annulus population. And so, you know, we're using quite a few 56 millimeter valves now. I don't know what the exact numbers are currently on, you know, the proportion of 56 millimeter valves used.
Maybe like about 30% now versus the 15% that was in the chart he showed.
Yeah. So that was certainly, and one of the limitations for all the tricuspid replacement therapies out there is treating these larger annular sizes. The second part of your question about the therapy in the space, I think that one aspect has been understanding the impact of tricuspid regurgitation and realizing the impact on not just morbidity, but mortality as well. Until the transcatheter era, you know, tricuspid valve repair as an adjunct to another surgical procedure was really the only option. Isolated tricuspid valve surgery was not really something that even our surgical colleagues were excited about.
I think with the introduction of now two commercial devices in our toolkit, and I'm sure that toolkit's going to grow, having an edge-to-edge option and a replacement option now allows for a very safe, minimally invasive approach, which we know successfully reduces TR, and we know that in turn makes patients feel better. I think that empowers patient, sorry, providers rather, who manage these patients to refer these patients that for the longest time have been languishing on medical therapy, and we've proven in both therapies that these interventional therapies are far superior to medical therapies.
Thanks. Matt Taylor with Jefferies over here. I'm just going to ask about the toolbox concept here. And I'm trying to understand how you're going to use the tools in the toolbox and how often. I guess I'll preface this question by saying we've seen some doctors to date take kind of a TEER-first approach because there's less risk of harm. But obviously, for a lot of patients, that's not going to be a complete solution. So after seeing these data, having the update on the EVOQUE data today, could you talk about how you'll approach patients in each position, how you think the split will be between TEER and replacement, and how you would segment those groups?
It's a great question and a very practical question. I think I don't see it as sort of a TEER or TTVR option. I think the reason I use the word toolbox is because, and I would challenge the notion that TEER is necessarily safer. I think ultimately, when we all see patients in clinic, our goal is to, first and foremost, identify what the problem is, and then our goal is to mitigate it. They're coming to us for a solution. So the question then becomes, what tool do I have in my toolbox to most safely, reliably, and effectively mitigate their pathology? And I think there's a whole host of factors that come into that. First and foremost, if we're talking about the tricuspid valve, the anatomy, you know, are there anatomical constraints that might limit me to one or the other, or sometimes, sadly, neither technology?
Are there patient comorbidities that, you know, might bear into the situation? You know, do they have conduction abnormalities? Do they have pacemaker leads? Do they have a degree of underlying RV dysfunction? Do they have pulmonary hypertension? What's their ability to tolerate an anticoagulant? What's their bleeding risk? So I think, you know, rather than thinking about comparing and contrasting devices in isolation, I think it's about balanced risk-reward with the devices that we have in our toolbox for the individual patient in the context of their comorbidities and their anatomy. If you talk about split, I can share in our practice, I would say our lean is more towards TTVR because we've had, we think we've got an excellent safety profile reflected by what we saw in the TVT Registry.
Ultimately, the reason we have more TTVR in our practice than TEER is coming back to that one fundamental question of how can I reliably get rid of that patient's TR. Because if I can do that reliably and reproducibly, that patient's going to feel better. In the majority of patients that we see in the context of their anatomy, in the context of their comorbidities, I'm able to achieve that with TTVR. That's why I have a slightly higher proportion of TTVR in my practice.
Thanks. Pito Chickering in Deutsche Bank. A question on the ENCIRCLE study. When you reviewed the trial design with the FDA and now you have the results, can you remind us of the FDA process and the timelines? Do you think we could see a similar pathway to what you saw with EVOQUE due to the success of the study?
Okay. Well, let me maybe just talk about the performance goal, but I'll let you guys talk about FDA, okay? So I think that the performance goal, so first of all, just to quickly review, we chose, the investigators chose, in collaboration with Edwards, a performance goal instead of a comparator group. And that was just, as I said before, because there was really no good comparator group for this patient population. These were patients who were unsuitable for TEER and unsuitable for surgery. So when it came down to looking at what the comparator group might be for an adequate performance goal, we looked at the medical therapy arms of the two largest randomized controlled trial studies in M-TEER at the time of trial design, which was MITRA-FR and COAPT.
These were patients with secondary MR, which was not all of our population, but predominantly so. And when you actually look at the means of those outcomes, it was actually slightly above 50%, not 45%. So there was a conversation around the advent and changes in medical therapy over the years and an agreement, so to speak, to reduce that to make sure that we maintain clinical relevance by challenging us to hit a performance goal of 45%. As you saw today, the outcomes far exceeded that with a wide margin with respect to the 95% confidence interval. And I'll let Edwards talk about that.
Yeah, as we've been talking previously about the timelines of our goals, I think at our last earnings calls, we said we were expecting approval by the middle of next year. But obviously, we're continuing to work with the FDA, and we'll give you updates at future kind of calls about how those conversations are progressing and updates on timelines then.
Thanks. David Rescott with Baird. I wanted to follow up on one of the prior questions around the toolbox approach, but more on the mitral side. You know, you saw ENCIRCLE data, and I think if you were to look at one of the more recent mitral M-TEER trials, the heart failure hospitalization rates and mortality rates were almost identical to what you've seen in some of those trials at 12 months. So when you think about, I guess the first part of the question is, why, you know, did you see such great outcomes? Does it have to do with the selections of patients in those trials?
The second part of the question is, when you think about, you know, expanding maybe the replacement applicability more toward a patient population that's getting TEERed today, how do we think about some of those trials and the evolution of the kind of dual toolbox approach for the market?
Sorry, just to clarify, are you asking why did we see such good outcomes in the M-TEER trials or in ENCIRCLE or in both?
In ENCIRCLE.
In ENCIRCLE, yeah. Well, I mean, I think that it comes down to reduction of MR. And what we saw is that greater than 95% of the patients had mild or less MR, and that was a really sustained improvement. So like Rahul was talking about on the tricuspid side, at the end of the day, resolution of the regurgitant lesion is going to be most associated with their symptomatology and their improvements. I think that, you know, as we think about expanding, you know, the toolbox approach, ENCIRCLE was in a population of patients who we thought were unsuitable for M-TEER. It's not black and white, right? It's sort of green, orange, red, so to speak. And so these were patients who were not ideal candidates for M-TEER, but it was also not impossible to do M-TEER.
And I think, you know, hence one of the reasons why we didn't randomize against M-TEER or medical therapy, because, you know, it's taken in the context of the patient that's in front of you as a clinician. And when we're enrolling patients in clinical trials, we're trying to manage the patient who doesn't come in with a stamp on their head, says, "I'm here for a clinical trial," or, "I'm here for an M-TEER," or, "I'm here for an M3 or TMVR." So I think that as we learn and as we digest the data and look into future investigations, I think that's what we're probably going to try to parse a little bit more, which patients are going to be best suited for each therapy.
One thing I will say is that TMVR in general, and I think M3 very specifically, has an opportunity to have a lifetime management conversation that we have not had before in the transcatheter treatment of mitral regurgitation. And what do I mean by that? What I mean by that, if you're a patient who has severe MR and you have an M-TEER, and it may be a little bit more common, in my experience and others, in patients with heart failure or secondary MR than with degenerative or primary MR, that they may have a recurrence of their MR. And when that happens with an M-TEER device or more often devices in place, that patient really has no good option, maybe other than heart transplantation, because their ventricle was already sick. They got an M-TEER device or two usually.
And then at that point, they can't get anatomically a TMVR. If we take that same patient population and we look to the future after having a successful, safe, extremely low mortality M3 based on the results from the ENCIRCLE trial, and we say five years, eight years, ten years down the line, I won't say exactly, nobody knows, but at some point, that patient may outlive their TMVR. Doing a repeat procedure in that patient is very, very simple. It's a repeatable event, just like doing surgical mitral valve-in-valve, and perhaps maybe even a little bit simpler. So I think we have a lot of options for our patients, and we're really excited about those options. And TMVR is bringing those options in a way that no other technology ever has.
I stole the mic from Dave. I was told to be very fast. So Danielle Antalffy with UBS. Just a quick question on mitral and patient, like the referral process, and what's it going to take? Because, you know, I was at the COAPT presentation years ago at this point, and I think it got a standing ovation, but, you know, here we are, and it's like so hard to find a mitral patient. So just curious, are we getting close to the point where, you know, the data is compelling enough that these patients are going to start coming in?
Yeah. I think it's, you know, it's a process. The same we saw, I'll make the analogy to TAVR, right, in the treatment of the aortic valve, that it took time. To be honest, I think physicians take time. We're a somewhat slow society, right? We are very conservative, I think inappropriately so, that we want to be cautious for our patients broadly. But I think that as we see technologies, and I'll, you know, again, I'll make the analogy, you know, TMVR really gives us the opportunity for the first time in the mitral space to have a surgical-like result in the abolishment of mitral regurgitation. And I think that's going to generate excitement. That's going to generate, and as this gets out, it's going to generate referring physicians looking at patients in maybe a different way, especially those suffering from heart failure, and it will incrementally improve.
But I think it's going to take time. It's not going to be overnight. But I think we have a lot to look forward to with this technology and the outcomes we've been able to achieve.
Thank you. So let me try to wrap up, you know, this session. I think it was another great, you know, conversation, a lot of excitement, you know, and I want, you know, to use the same kind of process. I want to start with, you know, what we knew before today and yesterday. We knew that, you know, we were having a very large unmet patient need in mitral and tricuspid. We knew that TEER, as a technology, was a great therapy, but also it was insufficient to treat all MR and all TR patients. We knew that EVOQUE was a great therapy to treat more TR patients. I am sure you have seen at ESC where EVOQUE, with EVOQUE for the most severe TR patients, we were able to show, you know, hard endpoint benefit.
But the question around, you know, the question on EVOQUE was around, you know, pacemaker and bleeding. So this is, you know, where we are as of, you know, yesterday and today. So what we learned today is the following: EVOQUE, even as a first-generation technology, has still excellent efficacy, is achieving hard endpoint for the most severe patients, and now is safe. And that's an important learning, you know, based on this, you know, 1,000-patient data set of yesterday. What we learned also today is that the M3, which is using, you know, the proven SAPIEN platform, brings the potential to physicians to treat, you know, more MR patients.
So again, what you can expect, you know, from us as companies, you know, we are going to continue to innovate so the physician has the best repair and replacement tool for both, you know, mitral and tricuspid patients. And we believe that each one of these categories, TEER for MR and TR, TMVR and TTVR, will be significant as category with high growth potential in the years to come. Again, so I want to thank our physician, Dr. Daniels, Dr. Sharma, you know, to be with us, to have been, you know, an amazing partner and PI and behind, you know, the studies and the platforms to bring, you know, this data to life. We hope that you are as excited as we are about our future as a company and the many opportunities we have in front of us to be able to help, you know, more patients.
And there are millions of them with today, you know, with no solutions. So if you have time, and we hope you do, you know, you can join us, you know, next door. I believe it is next door here on the right to this, you know, symposium about, you know, TAVR, seven years with SAPIEN, but also 10 years data about, you know, the PARTNER trials. And like, you know, Dr. Leon said, you know, more than 3,000 patients. Thank you so much for your interest, and I'm sure we are going to see each other on Thursday during earnings. Thank you.