Alan Wein: Hello, again. I'm Alan Wein from UroToday, and it's my very great pleasure today to have as a guest professor Emmanuel Chartier-Kastler from the Sorbonne University in Paris. At the 2025 AUA meeting, there was presented a new concept for an artificial urinary sphincter for urinary incontinence that I thought was extremely interesting because it presented a new principle. We've been using the same artificial sphincter or modifications thereof for a very long time since it was first designed by Bill Bradley, Brantley Scott. And so, I thought that this would be particularly interesting for the audience to see something new presented by basically its developer. So Professor Chartier-Kastler, please tell us about this.

Emmanuel Chartier-Kastler: Thank you, Alan, for this very nice introduction. Yes, we are pleased to work, to develop a new sphincter. It's always the same idea that the sphincter is made of an occlusive cuff, which is a hydraulic one. But what is the main difference with the legacy device is that there is only one control unit which is including the pump and the reservoir, and an internal battery, and all the electronic sensors and software which may control the full system. So it's an hydraulic system fully electronically controlled. And for sure in terms of surgery, the implant will be done either in males or females around the urethra at the bulbar placement or in females at the bladder neck level. So in males, it's placed at the bulbar urethra as we do with all legacy device implantations. But in female, it's more of an indication, not as well-developed as for males.

It has to be placed at the bladder neck level. So this device, as it's electronically controlled, there is a baseline pressure which is a pressure which is made to favor continence through the day. But what is very new is that with the patient remote control, the patient may at night decrease the pressure so it may protect the urethra with an automatic lying down pressure. And for voiding, the patient, I will show you the patient remote control, may open the cuff, and the cuff will be then refilled after urination. And because it's electronically driven, you may program the delay you want for the cuff to close after voiding phase. For sure, as for the usual device, it has to be deactivated for the post-operative period or for any incidental event in the medical life of the patient that you may deactivate it and put it fully open. So what is also very new is that as you don't have any pump, the patient has a patient remote control which may give him the possibility to void or to use a lying down pressure to deactivate. And as a clinician, we have a clinician programmer which may customize pressure, so at time of activation, we have to select the baseline pressure. So lying down pressure, everything can be programmed as you want. And there is also a specific function which is called a void timer. It means that if the patient don't use the device for at least 8, 10, 12 hours to select it, the patient, the device will automatically open. And so, we see that in the pilot study it has been used unfortunately. So what was the pilot study?

It was the first-in-man study overview. It's a basic study for male incontinence and patients have to suffer severe incontinence. It's based on a 24-hour pad test, and the follow-up of the patient is made after activation. So device activation is a baseline for the follow-up at one month and three months and thereafter until one year. So six patients have been implanted in two sites. And the primary outcome measures, as it's a pilot study, we were requested to look for safety. So it was to check about the rate of implants, explants and revisions at six months, and rate of device activations. For sure we are very interested by continence and we had to follow the FDA and the European community and French Regulatory's request, which is to look for patients who are at least improved 50% or 75% based on 24-hour pad test. And a lot of questionnaires have been used too. So for these six patients, the mean age was 71 years. These patients were suffering stress incontinence since a long time, four years. It's usual for these patients, non-radiation therapies have been selected not to get it before the surgery. And the duration of surgery was as a median 64 minutes. For sure, surgery seems to be quicker.

During follow-up, we had no explants or revisions at six months, and all devices were successfully activated. As I said, but we may discuss about it, one patient who suffered syncope and not related to the device was found with urine on him. And it's because it didn't go to toilet during 12 hours, so the device went to open by itself. And so, it was not scheduled in the study but we are grateful to the device that it's really working as a safety issue. And regarding surgical issues, some hematomas which resolved within two months after surgery and nothing very important. So what are the final results? Based on the 24-hour pad test at three months, six months, and one year after activation, if you just look on the baseline pad test at what is the 24-hour pad test at 90 days, six months, and 12 months, the improvement is always more than 75%, which is requested by the regulatories. This patient is very interesting because he had a good improvement at 83% at six months and he didn't request to increase the pressure, and thereafter we had to increase it.

You must know that increasing the pressure is very easy to do at the follow-up visits. And sometimes patients request for it, some not, so it's something we are learning. Regarding quality of life, questionnaires were reported but it's not a major interest for sure. There are very much improved on ICIQ-UI short form and I-QOL. What is also very interesting in the uroflowmetry is of high quality and at six months the Qmax as a median is 36 milliliters per second, which is very nice. And I would say which is far more better than with the legacy device because the cuff is always fully open with the electronic system. For women, we did the same study and we just reported one patient. And she was implanted, she was 67-year-old. She suffered severe incontinence, three to four pads a day. She has been implanted now two years ago with a robot, and now we can say that she was suffering on the one-hour pad test 124 grams, and she's suffering only four grams incontinence at one year. Now six patients have been implanted and we are on the way to report about it.

What is interesting in women is the quality of flowmetry, which is something fascinating for these devices because we have to improve continence but we also, we have not to have any impact on the voiding phase. So what we can say at this moment that for the males, the pilot study has been done as a prospective multi-center international study is running in SOPHIA2. Patients are included in Europe, in France, and in USA too. It started a few months ago. And for female, even the first woman has been presented, now six patients have been implanted and are followed and soon being reported. So as you can see we are on the way to have a new device which may improve a lot of what we could say pitfalls of the previous one, which is a nice one. But we can adapt pressure, patient don't have to push on any pump in the scrotum or in the major labia, and we can adapt pressure for lying down and baseline. So we hope in the future we will get the high level of results with the pilot study and go to FDA and European Committee approval. Be aware that at this moment this device is not at all FDA approved.

Alan Wein: Terrific presentation and an absolutely novel idea. So who is it who sets the baseline pressure? And is it only the clinician who can set the pressure or change it?

Emmanuel Chartier-Kastler: Yes. The pressure can be changed only by the physician at time of visits. And at the activation visit, we plan for the baseline pressure. And in the process of the clinical study we are running very slow from low pressure to higher pressure even if... You cannot refer to the usual pressures we are dealing with with the legacy device. Why? Because the device we are using at this moment with a balloon, usually we use a 61 to 70 centimeters of water. It's what is in the balloon on the bench, but you don't know exactly what is the exact pressure on the legacy device at the cuff place, because you have to add the abdominal pressure. And so, the pressures we are dealing with with the uroactive system cannot be compared by itself.

Alan Wein: And it's only, is there any way that the clinician or any guidelines about setting the pressure? In other words, do you use any urodynamic study or anything to guide you in exactly what to set the pressure to in men or women?

Emmanuel Chartier-Kastler: At this moment we have guidelines which are part of the study which are clinical guidelines without any urodynamic pressure assessment. What we know at this moment is that we have to use less pressure in women than in men. And we don't try to go too quick, because if we go too quick we may think that we may have too high pressure on the urethra. So we are increasing slowly at one month and three months follow-up visits.

Alan Wein: So basically you increase the pressure until you reach a satisfactory level of dryness?

Emmanuel Chartier-Kastler: Absolutely. And there is also something very different from the usual devices. For male patients, they don't complain at all about leakages when they are sitting and they stand up. The cuff may be empty because of pressure when they're sitting. With the electronic device, there is no reflux of the liquid inside the control unit. So there are some slight differences we are learning with the first patients who have been implanted, and it seems that the electronic system gives more facilities and more advantages we never had with the basic system, which is still efficient but with a fixed pressure.

Alan Wein: So what happens if the patient loses the control device or misplaces it or simply leaves it at home? "Oh, I remembered my car keys but I forgot the device."

Emmanuel Chartier-Kastler: You ask a very important point, and patients ask for this question when they are activated. They get two patient remote controls. And most of them they keep one at home, the other one with them in their pocket. And should they lose it, they know that within a timeframe which has been fixed with the physician, their system will open by itself. So they will be saved and then they can reactivate thereafter if they find again their patient remote control. So it's a good point and the future is probably not to have any more this patient remote control. It'll be the next step.

Alan Wein: Right. So what are the plans for further development and for submission to the regulating agencies in Europe and the US?

Emmanuel Chartier-Kastler: The plan is to finish with the SOPHIA2 study, which is including at this moment. I know that the process of inclusion is running well in Europe, in France, and in USA. So when it will be done, FDA will have to look for data and the final approval will come at this moment. The same for what we call the CE mark, which is absolutely mandatory to get any reimbursement and to be allowed to use it in Europe. So we wait for the Phase 2 study, what we call the pivotal study.

Alan Wein: So it looks like the results in terms of continence, it looks like it's comparable to the legacy product. In other words, it's as dry but not drier.

Emmanuel Chartier-Kastler: Yes, yes. Even if we don't compare both devices, because the study is not made for that.

Alan Wein: Right.

Emmanuel Chartier-Kastler: Understand as a clinician, my feeling is that we get the same results in terms of continence with an improvement in terms of continence when patients are coughing or running because we can adapt the pressure. If patients are coming back to the visit and say, "When I cough I have some leakage," we can increase the pressure and we can adapt. So it's probably something we are discovering at this moment how to manage the pressure with time with the patients. The idea is not to change it at every visit, but to find the good pressure for each patient. So it's a customized system.

Alan Wein: In terms of each particular patient. So then each particular patient after a series of visits will have their own individual pressure that seems to be not too high, not too low. And they basically can lower the pressure if they're going to sit for a while. They can lower the pressure if they're going to bed at night.

Emmanuel Chartier-Kastler: Yes.

Alan Wein: So presumably to reduce any erosion or anything due to the cuff.

Emmanuel Chartier-Kastler: They can do it by themselves. On the patient remote control, they have three buttons and they can use that. It's what is prescribed in the study. They have to reduce the pressure for night at nighttime and to reactivate when it's daytime again. And what we see in the study is surprisingly, no patients forget to use it. Because it's an electronic system, you have full control about what is the use of the patient, of the patient component of the device. So we learn a lot of things about the number of voids per day, number of voids at night. You know everything about the patient use of the device.

Alan Wein: Well, terrific idea. Congratulations on getting it this far. And really, good luck for the future in terms of the trials and getting it approved in both Europe, the US, and elsewhere. And thank you so much for taking time. For all of you who don't realize it, the Professor is actually in Paris recording this conversation, so thank you so much.

Emmanuel Chartier-Kastler: Alan, thank you very much for your time. And I hope study will end with fantastic results. We'll see.

Alan Wein: So do I. Thank you.