Edwards Lifesciences Corporation (EW) Earnings Call Transcript & Summary

Here in Boston, and we appreciate you all spending time with us as well as for those of you online. We've got a great session, I think, lined up this evening. And it's really the reflection of a lot of great news that we had over the course of this week. On Monday, the FDA-approved SAPIEN 3 Ultra with RESILIA. On Thursday, we got FDA approval for PASCAL to treat DMR patients here in the U.S. And today, we presented, I think, some pretty compelling data at the conference itself. So that's going to be kind of the flow of the evening session. I'll start by calling your attention to the forward-looking statement. We will, as we do, and these events have a tendency to make forward-looking statements. I would just call your attention to this. It's also available on our website, so please familiarize yourself with it. This is the agenda itself. So I mentioned it's about an hour session, we're going to break it up into 2 parts. The first portion of the session, you can see we've gathered some of our TMTT leaders here on stage with Mike, and they'll go through, again, some of the events that you've heard over the course of this week as well as a synopsis of the data that was presented today at the conference itself. We'll have some Q&A after that, and then we'll bring up Larry Wood and Dr. David Wood to discuss the TAVR portion of our business. We'll also break there for Q&A as well. And we'll look to have you out of here in about an hour. So once again, thank you all for joining us in person. Really appreciate it. It means a lot that you're interested in Edwards, and I hope this will be good -- nice for you all. So with that, I'll turn it over to Mike.

Yes. And I'll just add my thanks and welcome to all of you. It's great to have your interest in Edwards Lifesciences. Fun to be back to TCT to be with all of the clinicians and with all of you, and it's been a fun time for us and getting a chance to talk about what's new in TAVR and what's new in TMTT, especially with the CLASP IID results is something we look forward to and being able to meet those trial endpoints are something that we're obviously very proud of. We've got a distinguished panel that's going to help us discuss that. But before we get there, I just want to do a quick introduction. One of the guys that's not with us, this evening, is Bernard Zovighian. He runs our TMTT business. He's very disappointed not to be here. He's attending to personal medical situation. It's going to knock him out of commission for a couple of weeks, and it just kills him because he's put his heart and soul and he's an amazing leader, and I know he's going to be coming back here in force. Let me turn my attention to Dr. Ted Feldman. He is our Senior Vice President of Global Medical Affairs for TMTT. So he's really been one of the partners for Bernard as we've crafted the broad TMTT strategy. And he's regarded as truly a leader in interventional cardiology with a particularly deep history in transcatheter mitral and tricuspid. He has been one of the pioneers in structural heart space for a long time and personally performed thousands of those catheter-based procedures before he joined the company. And also joining us on the stage is Dr. Scott Lim, and I know a lot many of you are familiar with Scott. He's the Professor of Medicine and Pediatrics at the University of Virginia, and he directs The Advanced Cardiac Valve Center. But in addition, he's just been instrumental in so many transcatheter valve trials and been one of the -- he is one of the principal investigators for the CLASP IID trial. So we're honored to have those 2 guys with us. And with that, I think, I'm going to turn it over to you first, Ted, for a little summary of what we saw today.

Yes, I would like to just very high level summarize the outcomes of the CLASP IID randomized trial and registry. Of course, a huge amount of work to get these trials completed and reported as we did today. These started just ahead of the pandemic, and we found the pandemic created an enormous challenge with trial enrollment, which led to our use of a Bayesian design to allow an early look at the data before we completed the full randomized cohort. And what you saw today was the successful result of that early look. So we were able to analyze the outcomes in 180 patients randomized 2 PASCAL to 1 MitraClip for noninferiority of safety and effectiveness. And both of those endpoints were unequivocally met with a very narrow confidence intervals which is the major success of the trial. The one surprise finding we had in the experience is that when we looked at the MR, the mitral regurgitation reduction, in PASCAL and then in MitraClip, we saw both technologies reduce MR to 2 plus or less highly effectively. The PASCAL group had a very stable reduction to 1 plus or less in a large proportion of the patients. And in contrast in the MitraClip group, we saw some degradation of the initial 0, 1 plus best results over the 6 months of follow-up. So those are the high-level major findings. And, Scott, I'd like to ask you to comment maybe on your couple of largest takeaways.

Yes. Thanks, Ted. Thanks, Mike, for having me. And number one, I think the most important thing is that we have not had clinical trial work in this space for what, about a decade. So I really want to say thanks, it took a village of my colleagues at Edwards and my colleagues in medicine all around the world doing this, and I'm sure this is the first you'll see it multiple now that we're going to invigorate this space. Number two, for TEER technologies, TEER therapy in general, this really showed, as you said, a very high rate of success in terms of safety and efficacy in both arms. And that's an important takeaway because as we're going to be looking forward, this is just in the very high -- the patients are at very high risk for surgery. But ultimately, we're going to start going in lower risk strata and that 1 plus or less group that we're seeing were also achieving a much higher rate of repair that maintained 1 plus or less than we've ever seen before. We need those kind of results to go on to the next step. And I think we saw that today.

So with that, maybe we'll just go right to Q&A related to TMTT. Hold your TAVR stuff to later. And Mark, why don't you MC us a little bit here.

Perfect. Sounds good. First question. Larry.

Larry Biegelsen, Wells Fargo. Mike and Dr. Lim, congratulations on the CLASP IID results. Mike, one quick one for you. Just do you think this data supports premium pricing in the U.S.? And second, Dr. Lim, the waning efficacy that we saw or the MR reduction that we saw in CLASP IID with MitraClip. I don't know if we've seen that in at least the MitraClip registries. So how real do you think that effect was? And do you think will -- that will be confirmed when we see the full data set? And if it is, if we do think it's real, what do you think is driving that?

You can do the first part.

Sure, I'll do the first part. So thanks for that, Larry. And much like we have dealt in Europe, we feel like PASCAL is a premium superior technology. And so our intention is to have a modest premium versus what's available in the marketplace today.

So as far as your second part, we, actually -- there are 2 recent, in the last few months, publications of registries out of Europe that similarly looked at head-to-head MitraClip versus PASCAL and similarly gave a finding of some decreased efficacy over time in the MitraClip arm and not in the PASCAL arm. Having said that, our trial, too, it's still in the early look. This is still only 180 patients, and it's still only 6 months. And that in the grand scheme of things, we really need longer term data, and this trial is designed to give us that. We'll follow the full cohort of 300 out to 5 years and ultimately report out on that. So...

Yes, I think that's right. Clearly an early look because this is certainly not definitive at this stage of the game. Yes.

Josh Jennings.

Josh Jennings from Cowen. Echo Larry's, congratulations to all of you on the trial results. Dr. Lim, I was hoping to just better understand or maybe you can help us understand just the percentage of TEER -- mitral TEER procedures that are being done today in the United States of FMR versus DMR maybe in your practice, just -- and just thinking about what this approval that we heard of earlier in the week, kind of opens access to for PASCAL, what percentage of cases that -- case volumes today will PASCAL have access to? And then do you expect off-label use FMR, there's 3 questions in there, but ask me to repeat any.

Good to see you again. So a couple of things. One is, my practice is a little bit different. It's -- I'm at a small city, a very academic center. And so it's expected by referral lines from all of the state and surrounding states. And so for a number of years, when we were first getting into this, we were the only game in town or the state or surrounding areas. But I have to say, Abbott has been very aggressive about opening up small hospitals all around us. And so my referral patterns have shifted a lot. And so the straightforward FMR I tend not to see so much anymore because, I think, the mall community hospitals all around us are doing a lot of that. Having said that, I still think they're scratching the surface in the total volume of FMR that's out there. And it's going to take a longer-term educational effort by our colleagues at Edwards and so forth of trying to really show the value to our heart failure colleagues of treating functional mitral regurgitation.

Scott, let me stop you. I mean, Ted, do you have an impression in terms of your experience in terms of how much DMR versus FMR, you can speak about it either in the U.S. or more broadly or...

Yes, We have a lot of information broadly from particularly the TVT Registry. And just look at the national trend, I think, what Scott sees is very clear from the perspective of established sites look at the aggregate of now several hundred sites, I think the total is over 500 at this point, performing mitral TEER. The split is typically now about 70-30, 70% FMR, 30% DMR. What is uncertain there's a group of mixed etiology where they truly have features of both pathologies. And that proportion is an eye of the beholder kind of thing. And to give you an idea about that, our [ core abs ] argue about individual patients, whether they are FMR or DMR or mix. It's not always a very clean dichotomy. So that 70-30, if you used to have lens it might be 60-40 with 40% patients who would meet the indication that we now have, it might be 75-25, and that is something we'll understand better as we gain commercial experience.

And to go on another part of your question, I mean, it's clear what Edwards is going to do. We're going to be super straight on this. We are only going to promote this clearly for our label, which is degenerative patients only, not functional patients, not mixed patients are going to be our only promotion. Physicians have the opportunity to do what they wish. And I don't know if you want to comment on that, Scott.

Sure. I mean, I've been really encouraging my colleagues. We have an ongoing trial in FMR, the CLASP IIF trial, and we've been actively trying to educate and recruit patients into that trial because I think that's important. We need -- we've only had a few shots on goal in terms of the FMR world, and I think, we need to add to body of [indiscernible].

Thanks, Scott. Joanne.

Joanne Wuensch from Citi. Two questions. First one for Mike. Now that you have FDA approval, a little bit ahead of schedule. How do you plan on the commercial rollout? And I'll ask my second question for the doctors. It looks to us like the TEER market has stalled. Do you have an opinion on why that has happened? And what has this data due to the market growth rate?

Yes. Well, thanks, Joanne. As you guys might imagine, getting ready to launch is not a 2-day or a 2-week or a 2-month exercise. We plan this well in advance. So the idea of actually hiring a team, not only of salespeople but clinical specialists is something that we start to work on probably nearly a year ago, if not more, and we go through the very rigorous training. People don't get fully certified to be able to do their job at Edwards for more than 6 months' worth of work. So this approval clearly came earlier than we thought. We have a team that's ready to go, but that's a smaller team, and that will be growing over time. But although I'd say we're ready, we have the supply, we certainly have the will and the desire to do it, this is going to be more of a gradual ramp given the early timing. Yes.

Do you want to take your question?

Please talk about what you're seeing for...

Sure. I don't think it's the TEER market for the TEER. What I do in TEER, it has stalled, I see it shifting. We're actively seeing a lot more referrals for clinical trials in intermediate and lower-risk patients as well as increasing for complex patients that then we also are looking at other options if they are not TEER candidates to like TMVR.

So that said, I think many centers are still struggling with staffing shortages, and it's typically nursing and technical staff so that there may be operating room time that has to just be left idle.

Absolutely. No, we've -- our number of TEER procedures may actually be holding steady, but our length of time to scheduling is significantly increased because we have staffing issues related to pandemic.

Cecilia.

Cecilia Furlong, Morgan Stanley. I wanted to continue just on the topic of staffing. As you think about just getting the patient ultimately on the table. The challenges that you see on a relative basis versus TAVR, how we should think about that? And then just as you think about to rolling this out, patients today MitraClip -- or that really aren't eligible for MitraClip, patients then could transition to PASCAL. How do you think about just that bifurcation and really new centers bringing this on, how they think about the ideal clip for specific etiology?

All right. So the first one is about staffing, particularly as it relates to TAVR. And I think one of the challenges we found is TAVR AS has a mortality cost to waiting. And mitral valve disease, while there is, if you wait long enough a mortality cost, usually, it's this, they just can't breathe. They don't have a good quality of life. So as a result, we're trying really hard not to significantly extend out our TAVR waiting time at a cost of. Yes, for our patients with mitral and tricuspid disease, they have to wait longer. It sort of sucks for them, but at least it's not a mortality cost while hospital systems are trying to adjust to this new reality. I'm sorry what was your second part of the question?

[indiscernible].

So, yes, the decision we've got now essentially 2 devices approved. So the data has been embargoed to today, I couldn't talk to my colleagues. I kept my mouth shut. And we will function as a heart team. And so that's one of our to-dos when I go back. Now with my whole group, we'll talk about the data we now have and come up with an algorithm, how we're going to approach patients. But I think we've really bought into that heart team concept. And so that's the next step on our to-do list.

I'd say another really big factor that I hope comes out of this meeting is a recognition that the TEER outcomes overall keep getting better, and they've reached a remarkable outcome level now. And I think that's going to raise all boats in terms of this whole process of decision-making about which device. We had a noninferiority trial and met that end point, what -- a trial like this doesn't capture our user preferences, ease of use and special situations. And certainly, early on before we have our full data set, those are going to drive a lot of the decision making.

Yes. To add on that, to be fair, it is really hard to quantify that sense of getting stuck in cords with the MitraClip and the OSH moment that unfortunately, in this trial translated to 1 patient mortality too versus with the PASCAL, it's smooth, rounded edges and you're able to slide in and out of places that previously you'd get stuck. So I don't know how to quantify that, but that does matter.

Vijay Kumar from Evercore. Congrats on the IRD results, impressive. Maybe Dr. Lim, my first question for you about -- you spoke about MR 1 in the sustainability, durability of response, a higher percentage of patients on PASCAL did better. You cited those 2 registry studies in Europe. If you had to guess your opinion in why PASCAL is doing there, is that a design, and how important is this MR 1 or lower? Is that big enough clinically to more market share?

So I'll answer that part of the question first. I think from -- and I'm not going to speak as the market share. But as far as the physician and the patient in front of me, ultimately, what we're all trying to do is get surgical-like results, not just any surgeon, the best surgeons in the world results, which have 0 to 1 plus MR after repair of DMR. That's what we're shooting for. And the ability to get that and sustain that, I think, is very important. Mechanistically, there are certain design features of the PASCAL that we've all been hoping would get us there. And perhaps this is an early indication that we're on to something. But it absolutely needs to be followed up more. This is still a small number of patients early look.

Robbie Marcus, JPMorgan. Two questions. First, you had a question before about slowdown in structural heart and mitral. How much do you think is staffing versus maybe data? And is there a difference in the U.S. versus OUS with the positive overwhelmingly positive COAPT data with functional and MITRA-FR in Europe? And then second, how do we think about where you stand in enrollment for the functional trial?

So as far as the slowdown in being able to do cases in structural heart disease, I think it absolutely is a real issue as it relates to our staffing in the United States. As far as it relates to data, I think the interventional cardiologists in the United States have really bought into the COAPT data who hasn't as much as in the heart failure community and in part because the heart failure world has shifted very rapidly even since the COAPT data came out with the new drugs that really are significant SGLT2 inhibitors and so forth. And so I think that needs more of both study and more education to really figure that out for them. I think we'll get there, but that is part of why it's not exploding even more. There is a difference in U.S. and the EU when I talk, particularly with my French colleagues.

Yes. So I might take a shot at the EU and kind of feel free to jump in here to provide more of a clinical perspective. But MITRAL-FR definitely has some kind of impact on the mindset in Europe. And so when we go through some of our -- this COVID that we've been working through, we definitely feel like the growth rate we would have expected in transcatheter mitral which should have been higher than we've been seeing in recent quarters, and part of that is COVID and part of that is just this overhang that goes with less than convincing evidence. And it's one of the reasons why we think just the fact that this CLASP IID trial is out there. And here's another randomized, highly scientifically performed trial says that actually both therapies are performing at a pretty high level. It's much more contemporary. And you would argue that MitraClip today is performing at a higher level than MitraClip was 5 years ago and certainly comparable, at least with PASCAL, that, that has the possibility of transferring across the pond and actually having some kind of an uplift, but it's very hard to quantify, right.

Yes. I would say, additionally, a really important factor is that therapies for complex diseases typically have not moved to guideline Class 1 level indications, which is what really drives overwhelming adoption until there are several concordant randomized trials. And a good example of that is cardiac resynchronization therapy for heart failure, where there were something in the order of 5 randomized trials that drove the Class 1 indication for that therapy. And I don't know that we need 5 trials, but for the heart failure community to really enthusiastically embrace TEER for functional MR we'll probably require additional, not necessarily randomized trials, but large trials with very powerful clinical outcomes. The CLASP IIF trial enrollment is ongoing. And now that we have completed IID and have commercialization, the emphasis on IIF is going to be really greatly amped up. So we just have to keep working on.

But no updated status, Robbie.

Shagun Singh from RBC Capital and congratulations. I was just wondering, how you're thinking about patient selection and building the patient funnel. Is there a pent-up demand? Or will it take time to source these patients? What's your approach there? And then also with respect to the learning curve, is it just one procedure that is required? Or is it the longer [ ramp set ].

So I'll answer the second part first. There is a learning curve to PASCAL. I personally went through it myself too. The data we have, which I think tomorrow go into even more so on a deduct is that it's overcome after the first patient, and the second, third and fourth and so patients, then it's down, it's flat. It's very similar to what very experienced MitraClip operators are getting in terms of their procedure times with MitraClip. So there is a learning group. It's just relatively short, at least from the data we have. And I have to -- the caveat to that is that was 54 sites of the world's experts of TEER therapy. Sorry, what was the first part of your question. Funnel...

Funnel in terms of patient demand.

Yes. So I think that's a really hard one to tell you. We're seeing the patients in clinic. There's a lot more patients just out there, and those that we're seeing in clinic were not -- there is a funnel to getting them their procedure. How much that is? I'm scheduling about 3 months out right now.

On a broad scale, the population of patients with severe mitral regurgitation and symptoms who might be considered for TEER therapy is larger than the TAVR population. So the challenge of diagnosing these patients efficiently and then translating those diagnoses into thorough evaluations and ultimately, referral is enormous.

Marie Thibault from BTIG. I wanted to ask a question here on the forward-looking trials, things like primary where we're comparing TEER to surgical, is CLASP IID in your mind kind of an inflection point for TEER? Or do we need to wait for those kind of comparisons against surgery?

No. Well, I think, CLASP IID is going to greatly boost the potential for enrollment in those trials. There's been some hesitation among some TEER sites to randomize patients in these trials because of lack of confidence in TEER as equal to surgery and in other centers kind of the other way around. And now that we see these results with very high rates of 0, 1 plus MR acutely from TEER, I think many interventional cardiologists confidence that they can randomize the patient in this trial and that we might see outcome results that are on a par with surgery are tremendous. There are differences between the 2 trials comparing TEER and surgery. The primary trial is patients over age 65, and it's looking at a non-inferiority outcome. And with the results we see now, this could be quite achievable. The primary trial that I get these -- which reduce MR -- repair MR is the non-inferiority trial. Primary is the superiority trial, all comers, any age group, any risk level. And I think from a trialist perspective, because it's a superiority trial for surgery, if surgery doesn't win, then TEER effectively doesn't win, but achieves noinferiority by default, not by trial. And that's -- I don't think we would have thought about it as clearly that way before today's results were shown.

All right. How about time for one more TMTT question, then we'll shift gears to the TAVR team here. I'm going to go to Suraj.

Suraj Kalia from Oppenheimer. A question for Dr. Lim or Dr. Feldman. So if you look at the mention about deterioration of MitraClip's performance over 6 months. And please correct me if I'm wrong, some of the literature says that prognostic factor is the transvalvular gradient, like 5-millimeter of mercury or above. The CLASP IID shows about 2.5 millimeters and a substantial amount of the devices were the Gen 4 MitraClip. Is this just lot of small numbers and we shouldn't really read too much? Or is there something else that I'm trying to reconcile that the transvalvular gradient was relatively similar. So it shouldn't fall into the category of bad outcomes like other papers I've talked about and what possibly could be going on?

Let me -- the very simple answer to that question. In the randomized cohort of CLASP IID, the patients were all selected with a minimum valve area of 4.0 square centimeters, which is generous. It's easily enough for 1 and often 2 devices and greater than 4 square centimeters usually tolerate 2 devices or sometimes more. So that this group doesn't reflect a stress on the potential for gradient formation after either therapy. So the mean gradients at 6 months for both devices were below 4.5 millimeters of mercury. Our registry group had 18 patients with valve area between 3.5 and 4 square centimeters. And that group had slightly higher gradients with PASCAL, but only slightly higher. So definitely gradients are rate-limiting step, at least 1/3 of the COAPT patients had gradients over 5.

Yes. Although I think a little bit that's mixing apples and oranges because clearly, the data from COAPT in functional MR says those patients as long as you reduce the MR, they'll tolerate increasing degrees of MS. But the other data we have is for degenerative, which is CLASP IID that they don't tolerate creation of significant MS. Having said that, I think we're still just, we're learning about this and this device. So everything that we've said so far and learned about gradient relates to the MitraClip, which is a very fixed rigid device. PASCAL is bigger and it's flexible. And so when you put it in and you step on the fluoropedal and watch it throughout the cardiac cycle, it flexes open and close, so that in systole it actually closes where the force is coming, it closes the valve a little bit better, so you have less MR. And in diastole, it flexes open a little bit. So you have less MS, mitral stenosis. And I think we're still learning about then how do we interpret your question in gradients in the setting of this newer flexible device. So I'd say we need some smart people to help me dig down on that some more, and then we can come back to you.

Ted, thank you...

Yes. Thanks so much, Dr. Lim and Feldman, really appreciate it. Great work. All right. We're going to transition to talk about TAVR. This will be a fun part. We're going to get a chance to go deeper with that. And I'm joined by our global leader, Larry Wood, who I think many of you know and also Dr. David Wood. And Back to David Wood is a leading interventional cardiologist at Vancouver General. He's the Professor of Department of Medicine at the University of British Columbia, Co-Founding Member of the Centre for Heart Valve Innovation in Vancouver and a real expert and have been a big part of this journey. The fact that we've got David wood and Larry Wood, I'm like yes. So you guys have got a chance to knock on Wood with questions. That was the best joke I come up with a short notice. Sorry about that. Anyway, wanted to take us to TAVR. Want to kick us off, Larry?

I'm really glad he's an amazing CEO. All right. So thanks, everybody, for being here. It's always a wonderful opportunity to talk about our Transcatheter Aortic Valve Program. It's been an amazing journey, and it's been a journey not just of technology but really journey of evidence. When you look at the series of trials that have been run in the TAVR space, it's really remarkable when we reflect back on it now from the days of PARTNER I in inoperable patients all the way through PARTNER III, where we're treating low-risk patients. But you've seen how the technology has evolved during this period of time as well from our original SAPIEN platform to XT and then SAPIEN 3 and our SAPIEN 3 Ultra platform. And sometimes technology evolves, but it doesn't necessarily demonstrate huge benefits for patients. But when you look at this data, you can see the benefits with all-cause mortality that's fallen precipitously. You've seen disabling stroke fall very, very dramatically especially from the early days. And then when you look at moderate or severe PVL, you're down to under 1% now. So it's really remarkable how far this has come. But the patient experience has also changed dramatically. The procedure time now is the median times under an hour. 80% of our patients are discharged the next day. And, I think, most importantly, for patients, 96% of them go home, and that's home to the home they come from. And that's something we really learned from the early trials. We always think about patients getting discharged from the hospital. We didn't necessarily track where they went. But if you're a patient, you can come in and you can have a relatively quick procedure, you can get discharged the next day and you can go home and begin living your life again. It really is a testament to this procedure and how much it's changed over time. So with that, I'd like to turn it over to my good friend, David Wood, who will go a little bit deeper on some of this stuff.

And I have to remain seated. Anyone who knows me, I'd like to stand up and walk around. So very briefly because I think it's always good to know who you're chatting with. I spend the vast majority of my time doing procedures seeing patients in Vancouver, Canada, structural heart procedures. I run large clinical trials. So we did the 4,000 patient complete TAVR -- complete trial. We're now doing complete TAVR looking at concomitant coronary disease. And I was fortunate enough to be part of this kind of global optimization part of the benchmark program. So we kind of optimized 70 TAVR sites around the world before the pandemic, and then we switched to virtual, and we're now over 200. So those are kind of where I'm coming from, primarily doing cases, running large clinical trials. And the final thing before I start is we are not related. Well, just because we look quite similar is all what I'm saying.

Not really [indiscernible].

Here we go. So we get builds in there. We're in the midst of a massive paradigm shift where we truly, truly, truly now are seeing TAVR as the default strategy. And whereas we were treating patients in their low 80s. We're now treating patients in our low 70s, and the guidelines have been updated in both North America and Europe to reflect that. We can now do TAVR or SAVR, surgical valve replacement in anyone over 65. That is incredibly exciting, and it creates opportunities and some challenges given that we've just been through a pandemic, where a lot of staffing, especially research staffing, if you're running trials, nurses to kind of come up with that. But the vast majority of patients now are not too interested in anticoagulation, and they're very aware when you talk with them, whether it's here in North America or around the world, about minimally invasive heart valve surgery, and they'd like to go home the same day or the next day. That is their preference. I think this is just amazing that the patients we're treating now, we expect might outlive the valve. That was not our thinking. Again, when I shave my beard it was gray, but during the doing early cases in Vancouver in 2005, 2007, we were just happy to do the valve. And if the patient survived till discharge, that was fabulous too. We are now doing people in their early 70s who have options and want to live another 20 years. The stat there that if you're 80, on average, you're going to live another 9 years. So the technology needs to match that. The durability of the valve needs to match that. And then when valves do fail because all valves do fail, we've been part of the VIVID Registry and others. We need a good solution for repeatability. So those are the 2 big, I would say, hot topics in the structural heart TAVR world is repeatability and durability. So with that, the repeatability we'll get to you in a moment, but the durability, that's why this is an exciting announcement, is we're now using this anticalcification treatment that is used in the surgical valves. Edwards valve is now coming over to both our workhorse valve, the SAPIEN 3 Ultra as well as to X4. So I'll take those in turn. But this is incredibly exciting to us because you already have a low frame valve, so you can do THV and THV easier than if you had a big tall valve and you have to put another big tall valve in, but now we're getting the ability to have that first short same valve to last longer, which is incredibly exciting, and it allows you to then think about sequencing. You have a 70-year-old patient, the valve lasts say, between 8 to 12 years, you now have planned for putting that second valve in. And if we can get that first valve to even last longer than that because of anti-calcification treatment, that is a huge boon for our patients. So here at SAPIEN 3 Ultra, our workhorse. This is the exciting announcement. We now have SAPIEN 3 Ultra with RESILIA. This is the [ workhorse ] valve all about the world. They've added in the extra seal insert to the 29, which is very, very nice. Those were some of the early issues we dealt with 15 years ago, rates, pacemaker rates, leaks. Those have largely come down nicely over the last 20 years. So it's very nice to see this in the SAPIEN 3 Ultra, and then this is the one that I think is a paradigm shift. This is huge. So you have RESILIA, so hopefully, the tissue will last as long as possible anticalcification, but this is the tick box that we've been talking about, I guess if it's 20 years old for the last 10 years. We wanted to do bespoke sizing. So if you come in as a patient, whether it's in Vancouver and in the world, we can give you the right-sized valve without paying a penalty. So basically, that variable valve sizing that I can go up by 0.5 millimeters to give you the right valve for your specific anatomy is huge. The fact that we've maintained that low frame height. So if I need to get coronary access because you have a coronary blockage in the future, you come in with a heart attack, that's greatly facilitated. The RESILIA tissue, obviously, lets these valves last as long as possible. And then the commissural alignment. I cannot tell you how important that is. We're basically trying to make transcatheter valves. When a surgeon goes in and opens your chest, they put it in, and they would never put a stent post in front of your coronary artery by being able to adjust the valve safely in the trial before you put the valve down and do your final implantation, you basically can have surgical-like results, but transcatheter, which I think is huge. So I think that's all I was supposed to say. We're on conclusions now. Patients are living longer than before, absolutely. So the way we now envision if you're coming in and you're 80, if you're coming in at your 70, you will need a second valve. So that sequencing now is front of mind. That wasn't the case 5 years ago. The lifetime management requires being able to do THV-in-THV. That's why in Vancouver, we like a short frame valve. And with regards to now adding in RESILIA to both the workhorse, SAPIEN 3 Ultra as well as in the trial. I'm on the steering committee. I sit in on the case calls every week for X4, the ALLIANCE trial, it's very exciting, where this is going.

So why don't you go a little bit deeper in the commissural alignment because it went kind of fast on that. So what does that mean? Are you talking about aligning the commissures of the SAPIEN valve with the commissures of the native valve, and what are the how do you do that? And why is it important?

Yes. Well, one of the things is you want to make sure you maintain coronary access. And so as David said, when a surgeon puts a valve in, he lines up the commissures -- and the commissures are where the leaflets attach, okay? Those are where the stent post is, where the leaflet attachment is. We call those the commissures. So your native valve has those, the transcatheter valve has those. And right now, when you put in a SAPIEN 3, the valve just goes in randomly, you can't align and so it just goes wherever it goes. But being able to line up those commissures helps ensure that you're going to be able to get good access to the coronaries, Usually, you can come behind the frame with the short frame and get behind it. But in the cases where you can't come behind it, you want to make sure you can come through the frame, and that's one of the reasons we have the larger cell design, so you can come through the frame and be able to access the coronaries. But if you put a commissures right over the coronary, obviously, that's going to be more difficult. So being able to wind it up. Now there's a lot of people who speculate there's other theoretical benefits of doing that. Because of the way the coronary blood flow is, there are some thoughts that you could get improved leaflet washing, that you could reduce perhaps instance of HALT and other things by having a more physiologically aligned valve now. Those are hypothesis right now. They have to be something that would be proven out in the trial. But I guess one of the things I'd say is commissure alignment can't possibly hurt you. There's no downside to doing it. So it's one of those things where we get to add a feature that could only benefit from you with no real downside provided it's easy to do and you're not doing it across the valve. You're doing it up above the valves. So when you cross, you know it's in the right location. Is that fair, David?

Absolutely. So I think having a simple system to gently move the valve, so it's commissurely aligned. So you're basically like it was during the first valve, the valve you were born with is huge. That's obviously more challenging if you have a tall frame valve and you're then trying to manipulate it. So this -- we've been working with you guys for years to come up with this commissural alignment, we did the first 30 run-in cases.

So Wood ready for questions?

Yes.

It's a great segue.

Usually, ask the question first David.

We'll try to get to as many of you as possible. Matt.

[indiscernible] from Barclays. So just following up, Dr. Wood on durability. So if you could talk a little bit about the conversations you have with patients under the age of 80 and its consideration of how long do these valves last and I don't want to do surgery first, which ones go, what percentage of those patients wind up kind of still going for surgery first TAVR later. And how do you see this RESILIA data and change kind of potentially changing that? And then I won't follow-up, if I could. I don't have a follow-up actually.

So I've had a privilege, not only in Vancouver, but to hear these stories going around, those 200 sites around the world. And patients want to immediately feel better, and they want to have the most minimally invasive procedure they can have. So if you tell them that the valve you're putting in, it's going to be easier to repeat the procedure and also it's hopefully going to last longer because we're putting in a treatment that's worked well in the surgical valves, and we're now putting it over to the leaflets of the transcatheter valve, that very much resonates. I think some operators need to be very careful that they're going to tell people that just 1 valve, they're only going to acquire 1 valve for life. I don't think that's borne out by the registry data or the data that's coming out. So I think we really need to plan for repeat transcatheter valves. A lot of our -- the research on doing on these trials is about when you would pull the trigger to do that second valve. We want it to be as long as possible without causing harm but also to make sure that sequencing-wise, hopefully, the portion will only need the 2 valves. But people want minimally invasive surgeries. And if they have a second procedure, they don't want to go for open heart surgery, they would like another minimally invasive procedure. That's very clear, not just in North America but around the world.

Adam.

Adam Maeder, Piper Sandler. This one is for Mike and Larry. I guess a similar question, but I'll ask it through the commercial lens and how do we think about the commercial impact of the RESILIA tissue on the SAPIEN 3 Ultra platform? And how much of a step forward is this does this result in share capture? And then just any initial feedback that you can share from clinicians at this meeting?

Yes. Maybe I'll start, and I'll just remind you of our surgical valve experience. So in Edward surgical valves, we introduced RESILIA into the INSPIRIS valve several years ago now, and it's an aortic valve. And the primary advantages were RESILIA tissue and it also had the ability to expand to accept a transcatheter valve later. And then more recently have introduced the MITRIS valve, which also has RESILIA tissue. The INSPIRIS valve sell at a premium versus our other valves, the significant one, and it's become the #1 selling tissue valve in the world. And the MITRIS valve is still young and -- but it's on a fast trajectory.

Yes. So in terms of the rollout, we just got the approval, and so we'll be scaling everything to begin rolling that out over the next several months. One of the things is we are going to make an increase to the list price. So we are going to go for a price increase with that. And so we'll need to work with our hospitals and work through contracting and run that all process. But we think the value proposition from RESILIA is very, very strong. And so we think patients are certainly going to benefit from this procedure. I think for us, it's -- we don't get share fixated. We we're focused on always making sure we're innovating. We're focusing on trying to making really meaningful innovations for patients. And we think the byproduct of our innovation is share goes where share goes, but we think we just strengthened the best-in-class platform. And that's always our goal to just make sure we're always ideally 2 or 3 steps ahead and let alone 1.

Rick Wise, Stifel. Dr. Wood, when patients come to you and ask you how long we might -- I'm asking this as a question, what do you say, how long will my SAPIEN 3 last? I know these are difficult questions. What do you answer? And now your thoughts and impressions what do you think -- what would you expect the answer to be with RESILIA and with SAPIEN 4 with RESILIA, what would your hope and agreement aspiration be for longevity for that device? Don't look at Larry before you answer.

No, what I was going to say it's the same thing I talked to all my residents and fellows that always talk to every patient like your own family member, and that's who I want treating me and my family. It's clear. We are very fortunate in Vancouver to do the first SAPIEN, the first SAPIEN XT, the first SAPIEN 3, the first X4. So we have some of the longest follow-up. We published 10-year data before anyone else in the world just because we've seen that. So we've been fortunate to see patients obviously a minority in the early group last 10, 12 years and then come back and get a repeat procedure. So while we're waiting for the partner data to catch up, especially the intermediate and lower risk for the long-term follow-up. Yes, I've been saying very similar to what we see in the surgical data from the different registries like TVT and VIVID that, on average, the valves are going to last 8 to 12 years. 1/3 might last less than 5 years for a variety of reasons like renal dysfunction, concomitant comorbidities, but that with the platforms we're using and hopefully, RESILIA is going to get us even longer than that. We have a good plan for how we're going to do the second procedure, and we're going to be able to do that without having to open heart surgery. That is the #1 thing people want to talk about right now in 2022.

I think the way we think about durability fundamentally is changing. When we only had a surgical valve to offer patients. Durability was everything because you had an open heart surgery. And if you need to get that valve replaced, it was a second open heart surgery, and no patient wants to undergo one open heart surgery let alone 2, so durability was everything. And even the way we think about durability, if a patient didn't have a second procedure, the way we used to measure was freedom from reintervention for open heart surgery. So if a person didn't have a second surgery, the assumption was their valve was durable during that time. Now that we have a TAVR option, patients tolerance for symptoms, if their first valve starts to fail is changing. And the fact that we have an interventional solution for these patients, they can get their valve fixed without undergoing a second surgery. I think it changes the way we think about durability. But if we can give you a valve today in 8 to 10, 12 years from now, we can come in and we give you that interventional procedure. Again, we just bought you 16 to 24 years worth of durability without invading your chest. And that's just a very different paradigm than when you're thinking about it just one surgery and then a second surgery. So there's a lot of good debate. And I think the jury is still out on it, I think there's arguments made on both sides about how this procedure should be staged. But for sure, the way we think about durability is evolving and changing.

Chris.

Chris Pasquale, Nephron. A lot of discussion about managing the patient over their lifetime. When you think about putting one balloon-expandable valve inside another one, how -- what percentage of patients have a large enough annulus at baseline that they're still left with a sufficiently large EOA after that second procedure. And how do you think about the puts and takes of that approach versus putting a supra-annular valve in there during that second case?

Yes. So great question. And there's a whole bunch of valve-in-valve both that's already available as well as that's coming down the pipeline. Within the X4 study, there's a 150 valve-in-valve piece there. We found and others have found that doing a short frame in a short range is pretty easy, and you can get a pretty nice result with pretty good hemodynamics. We're doing studies to look at that, comparing invasive and echo hemodynamics. It goes back to the earlier question that it's very important that when we're talking about this type of 20-year sequencing that you don't pull the trigger on the second valve too soon that you get on [ Goldilocks ] you find that sweet spot when you're going to do that. I'm not a huge fan of putting in a tall frame valve, especially if there's going to be another option for doing THV in THV or a valve-and-valve procedure because I do think that limits your options unless you're going to talk about valve modification and things like that.

I think the other thing, too, and you can comment to this, David, is I think the idea is people think this is like Russian dolls. You put in the first valve and then you put in the second valve, and everything just get like a lot smaller and smaller. With our balloon-expandable platform, you can over dilate that first frame somewhat. And so you can create a slightly larger opening for that. And remember, transcatheter valves tend to be larger than a surgical valve that would go into that same application. So if you're doing TAVR first and you have the ability to do a second TAVR and get a very similar results to the first TAVR I think that's been your experience as well.

And that's why I said like truly, I believe X4 is a paradigm shift because you're putting in the exact right size valve as big as possible without causing any mischief, rupture of pacemaker, things like that. So when you come back with the second valve, you can put the biggest valve in possible. Now we're talking about it being commissurally aligned the same as with surgery. That's a huge value proposition for getting it right the first time and getting it right the second time. I think that's the switch is that, instead of just being happy that you've got a valve in and the patient got home and they lived a few years. It's now, no, no, no, you need to think 8 to 12 years out. And that has started to resonate globally. And it happened during the pandemic. I don't know, maybe people were -- had more time to really think about that. So now this whole lifestyle management is the biggest kind of topic at all the meetings we're going to.

[indiscernible] it sounds like the best approach here.

Richard Newitter, Truist Securities. Just wondering on the durability comments here in RESILIA. How do we think about next-generation systems with RESILIA potentially accelerating adoption into some of the newer patient populations you guys are targeting that are less penetrated like low risk?

Yes. I think, first of all, I think there's a big head fake here that durability only matters to young people. If you're 80 years old, your life expectancy is about 8 or 9 years. And so if you get a valve at 80 or 82, you don't really want to be coming back at 89 or 90 and getting another valve. So durability matters to everyone. And probably the place that we see the longest interval between diagnosis to treatment and sort of almost a bias against treating as sort of the 80-year-olds. And we really need to make sure we have a durable valve for them. I think a little bit what David talked about. I think no matter what valve you put in a 60- or 65-year-old, if that patient reaches their normal life expectancy, you're looking at a 2-valve strategy. So then it becomes what do you, how do you stage that and what do you pick? And when I think about our valves, it used to be a lot easier in a sense because all we had to do is make a valve that was good for treating the index aortic stenosis and then we didn't really think about it after that. And because the procedure has gotten so good, we don't really talk so much about the interprocedural complications anymore. We don't really talk about those things. So now we've moved on to this lifetime management issue. And so we do think about the valve. It not just has to be a great valve for that index procedure, but it needs to be a great host for a future intervention. And then it also needs to be a great guest when you're going to use it again for that second procedure. So the demands on our valve development programs are a lot more than they used to be, but that's really what's feeding into this lifetime management program. And so making the valves more durable to where a young patient, you can have a 2-valve strategy rather than a 3-valve strategy, is still really important, but durability matters for everybody.

I think we haven't heard from [indiscernible].

Maybe just a question for Dr. Wood, and I apologize if it's naive here. But just on the commissural alignment feature with [ X4 ] TAVR outcomes are pretty strong right now. Do you expect an improvement in outcomes here? Or is this just more preserving coronary access and durability?

So it's an investment in the future. I think there's a whole bunch of theoretical considerations, better sinus washout, maybe it's going to translate also into better durability because you're putting in anatomically like surgeons do. We won't know that for years. But I think just like in that benchmark program where we talked about early on, 1% mortality, stroke, vascular complications, those are the leading centers in the world. 80% next-day discharge, readmission rates less than 5%, pacemaker rates less than 6%. We've now added in planning for THV in THV. Even though we don't have the evidence data, the basis yet, I think it's that important that you need to plan for that second procedure. So having a simple thing where you don't pay a cost for commissural alignment, it's going to allow you then in 8 to 12 years to do a better second THV in THV. That is absolutely worth it in 2022.

Maybe time for one more. Anybody who hasn't asked Mike, Bill or Travis. Anybody now. Josh.

Just one quick question on THV in THV. Dr. Wood, I'm pretty sure I heard your good colleague, [ Dr. Webb at TVT ] started talking about or citing that he is seeing more and more TAVR and TAVR cases come in, that we better get ready for more and more cases as we move forward. Maybe can you just help us understand where you sit, your practice, where you are in terms of the percent of your case or valve-in-valve or TAVR in TAVR, and what he meant with that TVT, if I heard correctly?

Yes. I think we're right here on the inflection point for when we're going to start seeing more and more cases. And so we had a meeting in Vancouver last week where leading surgeons all around, we're talking about in implanters a tsunami of THV in THV cases. That's not going to be for some time, like 2028, 2032 in that, that's when we would start to see the big. We've seen more in Vancouver just because we implanted so early on that we started seeing patients come back because we had patients out to 10, 12 years before other centers in the world. But I think the big increase in transcatheter valve in transcatheter valve we're still several years away for them. But everything we're doing now is going to prepare us to get better patient outcomes when it really starts to go up because no one thinks these valves are going to last for 30 years, right? They are going to fail, and we're going to need to treat them. If we could do it minimally invasively, that's better for patients.

All right. well, thanks very much, gentlemen, and special thanks to all of you in the audience. I think for those people who think that TAVR is mature, that's certainly not the way that we think about it at Edwards. We think there's much more to do, and we're excited about attacking the future. I really appreciate your interest in Edwards and special thanks to Dr. Lim and Dr. Wood for joining us this evening. Have a great evening.