Renal Denervation: Unlocking a New Era in Hypertension Care | LSI Asia '25

Chris Eso  0:00  
John, thank you for for joining us today. We are here to talk a little bit about renal denervation and how do we unlock value, but also this new era of hypertension care. So maybe we start with a little introductions of who we are, and I'll hand it over to you, Jie, and you can kind of introduce yourself.

Jie Wang  0:30  
I think you are the moderator. You will first.

Chris Eso  0:35  
All right. Chris Eso I lead M and A and venture investment for Medtronic. Been with Medtronic for about 15 years, and most of my time has been on the cardiovascular side. I actually came into Medtronic right after the acquisition of Ardian in 2011 in our cardiovascular portfolio. So my

Jie Wang  0:59  
name is Jia Wang, I was professor at Columbia University, and then now I'm still sitting on the faculty of Columbia. I started Reno denouevation with Marc, Marc Galvin on the Harvard Levine. A lot of people do not know their names. Actually, they are the really, the true inventors of the renal denouevation. So the preliminary clinical studies we did with the Hanson Gifford and Josh win trop and also Harvard Levine together in Nanjing. A lot of people did not know that we did seven patients there. And also I did all these very early animal studies for renal denervation in my lab at Columbia. Later on, I started a company named semap Because we believe there is a very, very urgent need for renal innovation criteria still needed to have feedback during the procedures. And also you need to map renal nerves and to do selected innovation to take sympathetic nerves away Kip parasympathetic nerves, that's what, where we started. The device already got approved in China, just one month behind the Medtronic is seeing cell in China. It's about a million dollar sell per month, more or less. And I stop here. So I leave all the questions for Kris. He's going to barbecue me up today on the stage.

Chris Eso  2:34  
And you're being obviously a little modest, right? So maybe take us back to that time. You know, back in 2005 I think it was or so, when it started, and how and why this came about in hypertension,

Jie Wang  2:50  
right? We had a patient who had renal policies, and combined with renal kidneys, she had a terrible pen, and we use every drug to treat her pen, but was not able to so Josh win Trump, the interventional radiologist that suggested I say that Jay and Harvard, forget about this. Let's do, you know, put a big 24 gage needle through here around the renal artery, inject the lidocaine. And her pen stopped, and we did not know her blood pressure. So before we went home, we went to see this patient. She told us, said, I feel very comfortable now. We said, of course, you did not have a pen. She said, No, no, no, my blood pressure gets better. That's why, where we started, that's really, really the renal innovation started because I have a background in physiology. I have a PhD in physiology. Harvard was a PhD student, an MD student. He quit from physiology. But we all have this basic knowledge about how the renal nerves regulate cardiovascular events. That's where we started.

Chris Eso  4:11  
And I don't know if many people know that back that backs No. So I think it's important that you start there and you and then we talk going forward of how do we actually unlock this new era of hypertension care, because for the most of us, right, we've only thought about hypertension care by pharmaceuticals and and the interesting fact, right is basically one in three piece patients are not controlled on their with their drugs, and they cannot get to a target, hypertension, high blood pressure score. And so there needs to be new therapies that actually come and address this, this major, major need. And so fast forward to call it 2010 2011 right? Medtronic. Make some investments into a company called Ardian at the same time, you know, you start your work in China and elsewhere, and it really kind of kicks off a lot of clinical effort. And so let's talk about the journey that we've been on up until where we are today. Right?

Jie Wang  5:21  
We all know renal denervation up and down. It had some good times. It also has some bad times, and people start to deny renal denervation concept. But however, we do know any new medical device therapies need about 10 years to develop. It's not not only for the renal innovation, it's also for drug with stance as well. So one more thing here we need to understand, as Christia said, the drug therapies, yes, it's very effective, and also it's already proved that safety and efficacy, but however, people in the pharmaceutical industry was for years, still looking for so called Super drugs, which is you have one therapy the last for many years or many months, and also it has a 24 hour always sound effects, and also less side effects. So we should look into this. Rdn actually is another super drug. But however, why is up in the down? Because it had, you know, please forgive me, you don't feel offensive here, Medtronic made some mistake. Okay, the mistake was to use drug therapy, to use a device therapy to beat drug therapy. That was a wrong concept, because renal generation just another drug therapy is not to replace drug therapy, but as a another alternative for physicians and also for patients to take drug this device therapy, the therefore, to avoid what we just said, the sad effects, the not long, lasting and particularly drug compliance issue.

Chris Eso  7:13  
Yeah, I mean, obviously, with the therapy and the ablation, it actually is an always on therapy. You're not having the ups and downs with the medication that you have, but obviously there's a desire that you continue to stay on the medication to stabilize and control your hypertension, and so that's the benefit of of the hypertension care today, having the combination of both the drugs and the ablation. So let's talk a little bit about the journey the last 10 years that we've been on Medtronic, you know, for the most part, leading the way, when a lot of other companies, after HD and three in 2014 kind of went to the sideline and said, Look, this is going to be a long journey. We don't know what that's going to look like, and we don't know the true pathway. Medtronic, true to form and wanting to create a new therapy and make sure that we adjust address huge unmet need, continued to invest heavily into the technology. Redid, the clinical program conducted five different clinical trials. I think that the total in the in the patient population that was treated was over 10,000 patients, and had a huge amount of data to go back to the FDA to seek approval. So let's talk about site map and what what you know how they're looking at this opportunity and how that played out over that same time, 10 years,

Jie Wang  8:44  
right before I talk about the summit, because I just criticized, I said Medtronic made a mistake, but however, now have to admire Medtronic, what they did in the Last 10 plus years. We have to realize the device therapy or device trial become a drug trial. It's really a drug trial. Is not a device trial anymore. The reason made a mistake because it did not realize is a drug trial. So if you look at a metro study, off Med, on med study, meaning patients did not take drug only look at it into the pure biological effects of the device therapy and also on drug meaning the device plus drug therapy is basically is a drug trial is follow the same principles as a drug studies, therefore to establish the really the safety and efficacy of the therapy convince physicians and also patients. This is a safe is very effective, but however, however, there is a clinical need, because right now the therapy is, you go to the. Renal innovation. You up late, renal nerves, mainly in many arteries, all the branches, and then the patients will ask you, said, Dr Wang, how is my procedure? Do today? I will say you have to wait. You have to wait, maybe days, maybe weeks, sometimes a month, you will see the effect of the therapy now, therefore, we developed this therapy called renal mapping, selected innovation. The therapy is really based on the very solid anatomy, physiology and histology of the renal nerves around the renal artery, because we know around renal arteries there are parasympathetic nerves, sympathetic nerves and the sensory nerves, and the responses of these nerves to intra renal artery electronic stimulation is different in terms of increase, decrease or no change in the blood pressure. For instance, if you stimulate the spot, which is sympathetic nerve, you will see increase in the blood pressure. Therefore, this spot should be ablated. So we call this spot as hot spot. The term is not only we use the now the old industrial use that, for instance, the people write the reviews, the pioneer in this field, Murray askler, post sabbatical, they all use these terms called hot spot that should be applied after ablation, in the same spot, you deliver the electronic simulation, you will see no increase in the blood pressure. You know you have very effective ablation. Otherwise you have to do another ablation. Therefore, the procedure is mapping ablation and the conformation you start this procedure from the very distal of the renal my artery, and also treat the entire renal artery, if you say, decrease in the blood pressure, you should not do ablation. Why? Because, if you look at the Medtronic data, alpha, Matt, unmat. And if you look at record data, which is the ultrasound ablation, only do ablation the renal battery, no matter what energy platform you use, the responder rate is about 60, 65%

Chris Eso  12:36  
initially, initially, and then it advances from there, right

Jie Wang  12:41  
now, still, I think 65 70% the reason for that because the percentage of the sympathetic nerves around the renal artery is about 70% if you do unmat, unmapped ablation, The probabilities is about 70% okay, so we did this renal mapping, selected innovation. We published this paper on length and E clinical medicine, we can increase the responder rate to about 80% so that's what we do now. So the device has been, as I said, prove the in China, we start to have our clinical program in us as well. Yeah.

Chris Eso  13:28  
And from the Medtronic side, the data that we've seen, it continues to increase in terms of the response rate out about a year, year and a half, we'll start to see it approaching that 80% and so you continue to see an increase of that response, which is, which is critically important, obviously, when you're talking this size of a patient population,

Jie Wang  13:53  
yeah, one of the differences I would like to emphasize here is we do not have a huge data yet, but because the therapy is already in the clinical practice in real world, and we do see the responders of these patients much quicker than on med rdn. So you we do see the reduction in blood pressure on the day one of the procedure. It continues now, one month, two months, up to three months, because we just seen the clinical practice in about four months. That's the data. We have more than 100 patients, yeah.

Chris Eso  14:41  
So let's pivot a little bit and talk about modality and the different modalities that are out there, RF, ultrasound, obviously, alcohol, right? Let's, let's talk about the differences in the pros and the cons of them.

Jie Wang  14:54  
Okay, I really love to talk about this, this topic. Because many engineers, they use a different energy platform, we answer into the renal arteries to do their innovation. So I think Rf is, I still believe RF the best. The reason I say the RF is the best because we understand much, much better, much, much clearer in terms of biophysics and the biology of RF, because every EP physician has to read biology and by by physics of RF in cardiac vascular therapies in terms of the parameters, the temperature, the impedance, the power, the blood flow and the structure of the arteries, almost in the everywhere You can use mathematical equation of physics, equation to define the RF and ablation, how much we understand about other energy sources or platform, much less than RF. Now, the data it showed, as I said, it's very comparable between RF and ultrasound. It's much better than alcohol. You know, alcohol, as far as that, they say, the data, I don't think that's good data, okay? Because you only see three millimeter different mercury, different between treating and the shame group. And also, P value was a point four, nine, right? It's, it's failed study. But for the ultrasound, they only tell you the half story. They said we need about eight seconds to do ablation, yes, eight seconds. That's after the broom in the right position. The time you cope you pull their trigger. So they only tell you the time to pull the trigger. They did not tell you the time to justify the proper balloon catheters in the proper size of the renal artery. Remember, there are seven sizes of ultrasound balloon catheters. Once you inflate the balloon and you need to shut contrast from the distal and if you don't see any contrast goes through, you can do the ablation. Otherwise you have to change another catheter. So the time to use the balloon Catherine, the proper renal artery. It takes time. So you look at the procedure, time is very comfortable between RF and ultrasound. That's my preference.

Chris Eso  17:52  
Now, some would some would argue that the ultrasound provides a 360, circumferential ablation. What do you say to that,

Jie Wang  18:00  
well, again, you need to look at the anatomy of renal nerves. Okay, so for RF, it's not difficult to do 303 60 around ablation, if you can do a lasso. You know, small lasso there. But why you don't do that? Because you do not want to create a damage in the endothelial cells around the 360 degrees. That's why Medtronic spiral device design as distributed longitudinally, five millimeter apart, and the 90 degree go around. That's the standard procedure. So again, the 360 degree ablation did not further increase the responder rate. So that's why come back to same app technology again. You need to do selective innovation. Need to map those nerves. You need to know where you should up late, where you should not, not ablate

Chris Eso  19:13  
Absolutely. So let's, let's talk about real world now. What are we seeing in terms of very

Jie Wang  19:19  
interesting impact? Right question, here in the real world, we see the reduction in blood pressure in those patients is better than clinical trial. And why is that? Three things at least. Number one, is a possible effect, plus true therapeutic effect, because that's number one, number two for our study, for our treatment, because those physicians, they map sites, much more than clinical trials. Okay, because in the clinical trial, we only. Allow the physic physicians to map one side at one cross section of renal artery. But now in the one cross section they map two or three sites, so you have more sites to ablate, okay, but still it's only about four the most the six ablations per renal men artery. Okay, it's less than Medtronic. Medtronic does like 2060, 2030, even, 40 ablations, the number three fact, I think the much more critical as well, which is in the clinical trial, those patients already on two, three, even four or five drugs. But in the reward, this patient said, I mean the 20, 456, drugs, actually it's not therefore, once you have therapy, it's more effective because they are now you patients, just like patient, never under any antibiotics. You gave antibiotics, you see effective very much. That's why we see much more effective in terms of reduction in blood pressure. In those patients in real world,

Chris Eso  21:12  
well, in and they're during the clinical trial, they were much more controlled, yeah, and compliant on their pharmaceuticals, whereas in real world life gets into the way, right? And sometimes you're not as compliant, correct? So let's talk a little bit about some of the new technology that's out on the horizon that, you know, we saw Boston do an acquisition of sono V, not a, I guess it was not a new technology. It's a it's been, actually around for a long time, but, you know, let's talk a little bit. Why would they, why would they jump back in? Because they obviously did an acquisition, you know, back in 2011 and and shut that program down.

Jie Wang  21:53  
I think because Medtronic, because Ricoh and because SMAP, we start to show the very effective therapy of renal denervation on those patients with uncontrolled hypertension. The indication, if you look at approved in us, it's very broader than any other countries, right? The people, after the change in their lifestyle and the drug therapy, they still cannot control their blood pressure. They should use renal denervation. They should have option to use renal denervation in China is much more restricted indication for Medtronic, the indication War Two. One was drug resistant hypertension. Another one is patients with drug therapy, but on tolerant to drug therapy. But for us CMAC, we have one more indication, which is patients want to reduce their drug burden because our clinical design, the reason why Boston bought something new, the best answer, or answers we should ask them. Okay, now we only can guess why they acquired this company. I think that one thing is because Medtronic, because of semap, because the record already in the real world to treat these patients very effectively. And I think RDA is a very few medical device therapies has such broader usage for cardiovascular diseases, because it's not only for hypertension. Hansen is sitting here, the first indication was not hypertension, was heart failure, right? So, and then change from heart failure to hypertension, and therefore rdn is not only good for or proper for hypertension, but also for all diseases with high sympathetic tone as a pathology basis or mechanism responsible for this disease, the reason Boston wants to buy already bought Sony view, I think this try to differentiate it from Medtronic. And also Sonny will claim they can cool down the ultrasound electrode without bloom catheter, just use blood stream naturally cool down the electrode. You know, let's see what we'll have. I wish them their best luck.

Chris Eso  24:40  
Yeah, absolutely, absolutely. And so then, what do you think is going to unlock this new era of technology for hypertension care commercially?

Jie Wang  24:52  
Okay, first of all, B is insurance okay? If insurance does not pay. For this therapy. I don't think the therapy will go to anywhere. Okay, we repeatedly approve that. Fortunately, maybe Kris, I want to be moderator asking you was, you know, insurance and the status in us, but I can tell you, in China, the insurance already cover rdn in Shanghai area. You know, if you look in China, you think is one country, but it's really not in one country in terms of medical insurance and reimbursement system. For instance, Jiangsu Province, which is our company, is located, is it has a three different systems. You have to find, always systems together, then get medical therapy. It's already got medical national, medical reimbursing, Shanghai, Suzhou, Xinjiang, Hainan, part of Wang Hui. But I think it's the progress is pretty fast, because we just got approved last year, start to get a sell the beginning of this year. But what's the status in us? I heard it's got into CMS. Is that real?

Chris Eso  26:16  
Yeah, we're working the CMS angle right now. We hope in the next couple of months, we'll have a national decision that will then go to the general public for comment, and by the end of the calendar year, we'll have some full reimbursement in place for the for the new calendar year, Kris, I want to ask You How much? Yeah, first, that's the billion dollar question per

Jie Wang  26:45  
but it already said in the same as the catheter for Rico is about $15,000 correct? I think so. Yes, the form Medtronic is 13, $12,000 right? Something like that, right? My colleagues asked me in China, said, Why do reimburse Rico more than electronic I said, you know why? Because they need to use more than two catheters per patient. That's why they reimbursement. That's why I tell you you need to change the different sizes in the different the renal artery. Okay, in China, I can tell you how much Balan Jo Kim bar is about near 90,000 RMB, Medtronic is about $10,000 more than us. But also, I just made a joke with Kris. I said I should tell you commercial team in China. Don't do this vicious, you know, commercial complications with us, because we just got news from the head of my commercial team in one bit in China. Go to every hospital you have have, you have to have a bidding process, okay? For this particular hospital, Medtronic bid as 1000 US dollars for their council. 1000 US dollars, how much we sell our console is about half million RMB. So we got really scared. You know, Medtronic is a giant. We are small, nothing.

Chris Eso  28:25  
Well, it's about treating patients at the end of the day, right, right,

Jie Wang  28:29  
right. So, in that way, we should have gave all these catheters out as a gift.

Chris Eso  28:39  
So where do we go from here?

Jie Wang  28:43  
I have to say, I have to say the real innovation is in it, very early stage. Okay, we have many, many questions have now been answered. We have many, many challenges have not been overcome. Okay, my team asked me, and also physicians in China asked me the same question. I said, you know, in the most is in the Sephora. Remember people in the audience, the first generation of the druggie booth stand named as a Sephora from Johnson Johnson. So to the most, the renal denervation therapy is filling the safer stage. Okay, so what do we really need? I think we need just we, if we look at a stand, the PCI therapy, we used to have bright metal stand, then we have drug eluted stent. And then we use imaging to decide which patient should have a stent, which patient should not have a stent, not anatomy imaging procedure endpoint during the person. Seizure now we have FFR. So the the FFR is the function that will have digital FFR, right? We have the D, right. We have digital FFR. And that is really the functional assessment for PCI, okay, it tells us that every therapy, it should have diagnostic and the therapeutic. Now, the renal denomination, except us, the only has therapeutic. It does have diagnostic. So it must have diagnostic which tell the physician where we should treat. How do we assess the treatment during the procedure and then use the therapy. That's what we need. And also, I think, it may need combined with a 3d imaging. So we have very clear information for the operators where we should treat, where we should not treat, and therefore we have much better we always call less is more Okay, so we should do less ablations, and then we have better outcome in terms of the safety and efficacy.

Chris Eso  31:17  
Well, we have a few minutes. Is there questions from the audience that we can

Audience Question  31:23  
address one. Thank you guys for for doing this and having this kind of organic, unfiltered discussion. Chris, I'm curious. You know, we do a lot of market research and reload innovation is one of the fastest growing markets that we can track. Obviously, it's new. You mentioned Medtronic, kind of taking risk in the early days, seeing the program through to this point. We talked a little bit about some of the others in the space. And, you know, Boston, with vesics and now sonovi, all these different things geographically, with reimbursement, new technologies in the ecosystem. How do you think, kind of, in your position at Medtronic, about like, where, where you start allocating your time, your resources, your investment first, when you're thinking about all the new companies, all the opportunities with your existing program, the competitive landscape, kind of just walk us through this as a case study for how you approach that.

Chris Eso  32:09  
Yeah. I mean, it goes back to when I first started Medtronic, even after the acquisition of arty, and we were still tracking close to 70 Reno denovation companies back then that were looking at all different aspects, diagnostics, the therapeutic, the mapping, the the confirmation, and as we looked at it right, the landscape, right, we think at the end of the day, there needs to be this ecosystem that goes around the therapy in order for it to get full penetration and full adoption, and so as we've looked at it now, obviously we feel very confident in our position with the technology, with the clinical data, with now getting the reimbursement in the next six months, we think we're in a really good position from the therapy perspective. Now we need to start to build out and around the therapy and the ecosystem to really drive the penetration and the adoption. One of the things that we didn't talk about was referral pathway, and that is going to be a hurdle that we're all going to have to figure out and work through, because the patients, for the most part, are not at the procedure list. They're at the general practitioner or or the hypertension specialist or the cardiologist. And so how do you get them to the interventional cardiologist, get them the therapy, get them treated, get them stabilized and and living very healthy lives? So that's really the next kind of new frontier of technology.

Jie Wang  33:46  
I really like to catch this moment. It's very precious time we have Hanson geffer, who found the renal innovation. I still remember the meeting we had in the building called Audobon building across Columbia, men building you and the MARC Dean, and also Marc Harvard and myself, with five of us to talk about to how to proceed back then that was no already yet. So we have Hansen here. Hanson, I would like to ask you, what are you wishing for the Reno division from now? And you know, anything you say here is very precious.

Hanson Gifford  34:30  
Well, you kind of point me out. I do remember that meeting in that little, that little room, you know, in the Audubon building. And I could, I think Marc Dean and I could see that we were in the presence of a really fascinating, important idea, and that you and Howard Levin and Marc Gelfand had come upon something that was real genius and an opportunity. To really change healthcare. And it's something I've learned over the years that really big new innovations, unfortunately for our industry, take 20 years, you know, from starting the eval company, developing the mitral clip in 1998 to that great event at TCT in 2018 when they said, Wait a minute, it is actually better than surgery 20 years. And I won't bore you with all the other examples, but it takes a long time, and I just tip my hat in particular to Medtronic for their persistence. It has taken much longer than anybody expected, more money, more persistence needed, and you've done that. So really happy to see this day, this year coming where finally we are going to start helping patients, which is really what this is all about. So thank you. 

Chris Eso  35:58  
Thank you. 

Jie Wang  35:59  
Thank you. Thank you. Hanson was very brief to take the rdn concept from Marc Harvard, because we went to many VCs. They kick out, kick us out, because all these VCs and they understand, you know, screws, they understand. You know any other you know metals, but we, once we talk about RDN, that's really a unique situation in the medical device therapy, because if the treated disease is not a via physics, but via pharmacological pathway, therefore, a lot of these VCs we went to, you know, we have several guys sitting in the room. The one guy said, I had, I have to take a phone call, never come back. Another one said, I need to run to the airport. They never come back. And finally, one guy said in the room, said, you know, ask a couple questions. We said, Thank you so much. He said, Never mind. I'm an intern here. Okay, that was really, really the true situation. But we caught Hans. I think Marco Harvard called you. You flew to New York City by Red Eye fly. You know, they were really sensitive to a new technology, and catch that new idea right away. We did not try to convince you. And also, once they saw this, a publication by a group of the physicians from Boston, they did those. They cut the nerve around the spinal and really establish the physiology basis for this treatment. Therefore, I want to ask the audience the any questions you have for Hanson here, not only for Me and Kris here, that's the best time to ask. So you got scared of Heinze.

Chris Eso  38:18  
Well, if, if there's no other questions, then maybe well, thank you appreciate the time and the workshop and that we're continuing to unlock this new era of hypertension care. So thank you all.

Jie Wang  38:31  
Thank you so much.