Kathleen Kobashi: Thank you. Thank you so much, Dr. Wein, for the opportunity to be here today. I'm just going to give a quick overview. This is a very exciting domain right now in treatment for urinary incontinence. So as you know, in 2024, the overactive bladder guidelines were revised and now it's no longer an algorithm, but it's more of a menu where we can go straight to minimally invasive therapies, which used to be called third-line therapies in the prior iteration of the guidelines. The other thing to point out is that we now include implantable and percutaneous tibial nerve stimulation, and some of that we're going to focus on in this brief overview.
I wanted to point out that in statement number 30, clinicians may offer patients with OAB minimally invasive therapies without requiring trials of behavioral non-invasive or pharmacotherapies, which is quite a change from the previous algorithm-type style. There are a variety of different neuromodulators in the options for neuromodulation, including chemical neuromodulation that's onabotulinumtoxinA, and then various modulators at the sacral level or in the tibial nerve level, which now include percutaneous, implantable, and even transcutaneous stimulation options.
So very briefly, sacral nerve stimulation has been around for more than 25 years. The optimal lead placement requires that the lead follows the nerve in the superior medial aspect of the S3 foramen and then travels laterally out to follow the nerve path. And in an ideal world, you'll really get successful stimulation and motor and/or sensory response in all four electrodes under two volts. There are a couple of different devices that are FDA approved. They're very similar in so far as the size of the device and the fact that they both have rechargeable and non-rechargeable options that are MRI compatible now with a battery life in the range of about 15 years for the non-rechargeable options.
So let's talk about posterior tibial nerve stimulation or tibial nerve stimulation. The mechanism of action of which is believed to be a retrograde stimulation of the lumbosacral nerves, L4 through S3, and this area has really exploded as of late. Now, the original iteration was a percutaneous version. Unfortunately, because of practicality, it really didn't gain as much traction as perhaps this modality might deserve. We have to complete 12 weekly treatments and then a maintenance, the frequency of which hasn't actually been hammered down yet. But meanwhile, we've got implantable versions that have now come out and there are two implantable versions that are FDA approved and available for implantation.
So I'll go over both of them quickly with some of the initial data. The eCoin Pivotal trial data at one year showed that 75% of patients achieved at least 50% improvement at 48 weeks. In general, people had very high satisfaction with all domains, including the programming, the device itself, and the stimulation. At about two years, 96 weeks, 72 patients completed that evaluation. And just suffice it to say that on a three-day voiding diary, 78% achieved greater than 50% reduction in their urgency incontinence. About half achieved greater than or equal to 75% reduction, and about a fifth of the patients were completely dry. And that amounted to about a three-episode-per-day decrease in urgency incontinence episodes in patients who started in the four range. More than 90% of patients did not require medications anymore after successful implantation. And so, it really shows that there's a continued favorable durable result with the eCoin.
Now, similarly, the BlueWind Revi device, a little bit different, it's implanted near the tibial nerve. As opposed to the eCoin, this is placed under the fascia and the patient has to wear an external stimulator, you can see the bracelet, ankle bracelet up there in the upper right, for about 30 to 60 minutes a day. No more than 120 minutes in a day. And similarly, their initial data has been very promising. So if you really focus on the right side there, at one year, about 82% of patients described greater than or equal to 50% decrease in their urgency incontinence episodes. So trying to compare apples to apples with the eCoin data. That was durable at two years. So nearly 80% of patients maintained that greater than 50% improvement at two years. There are a couple of additional ITNS devices that are anticipated, but they're not yet FDA approved, but in trial. So the TITAN from Medtronic and Intibia from Coloplast, so stay tuned on those that will become on board pretty soon.
The next iteration is transcutaneous tibial nerve therapy. This, there are several small studies that show some promise with the TENS unit type of approach. Overall, it's very well-tolerated. There was one study here that showed here on the right, you can see that the dark blue line is really their symptom severity. And so, the symptoms decreased rather impressively on this graph, and all the rest are sort of quality-of-life-type domains, all of which improved with this device. I think that's all I have for just a quick overview of tibial nerve stimulation and what's in that space and how the guidelines have changed focus just a little bit.
Alan Wein: Good. Thanks so much for that review. When someone comes to you having failed drug therapy and they want further relief and they have urgency urinary incontinence along with the urgency and frequency, they empty their bladder okay. How do you decide between a form of neuromodulation, onabotulinumtoxin?
Kathleen Kobashi: Well, one easy fork in the road is if they also have some bowel concerns, then I go to neuromodulation of some sort, typically sacral neuromodulation, because the onabotulinumtoxin is only going to help with the bladder. So that's kind of an easy fork in the road. Other than that though, I mean, it really comes down to patient preference. I mean, I think there are pros and cons to all of these minimally invasive options. When I talk to the patients about onabotulinumtoxin and say that they have to come in every six months on the average, six-ish, six to nine months, some of them are thrilled that it's that long and some of them are like, "No way I'm coming in to see you every six months." Some of those practical things that are not even the clinical results are deciding factors for some patients.
And then when it comes down to tibial nerves, the implantable tibial nerve stimulators, now it's very encouraging to see the data looking pretty promising and some of the head-to-head stuff is looking like there's some comparability with sacral neuromodulation. But the question is if you're going to need an MRI or something, then that becomes an issue. So there are some practical things that you need to tailor for the patients, but I just present the pros and cons of each of the options to the patients and let them decide.
Alan Wein: So when they tell you, "I saw on the internet this thing where someone can just implant something on my nerve and then I can wear this wraparound thing that I can control the stimulation myself," does that really work as well as the sacral neuromodulation, which I've seen a bunch of stuff about on the internet? I mean, what do you tell them?
Kathleen Kobashi: Yeah, so obviously the jury is still out there. I mean, I think the fact is that the further away you get from the nerve, very likely, the less, I think, in theory, at least you would think that the less efficacious it would be. I mean, obviously the data there is small. There are a few series and it's a TENS unit, basically. I mean, I think for the right person, if they don't really want to undergo an invasive procedure and they're willing to, I mean, again, perhaps give up a little bit of efficacy, that's okay. I think, again, going through the pros and cons of each of the devices and how immature the data is on some of these, it's developing and getting more mature every day, but we don't have a long track record, even with the implantable tibial nerve stimulators yet if you're looking at a 25-year track record that you're comparing to with sacral neuromodulation.
Alan Wein: Do you think that transcutaneous stimulation will ever become a reality? Because obviously if it does and it's comparable, then it really sort of takes away all the other option.
Kathleen Kobashi: Yeah, that's a really good question. The question is, are you able to target the nerve and apply the amount of energy that's necessary to get a clinical response through the skin? I don't know, I mean it's hard to predict, but I will be pleasantly surprised if that comes to pass.
Alan Wein: If SNM doesn't work, then in most people, does Botox work, assuming there are no contraindications? I mean, assuming they empty their bladder and the problem is not any sort of retention or anything like that, can you give Botox afterwards and expect some reasonable success?
Kathleen Kobashi: Well, the fact is it's a different mechanism of action, so I don't know that one predicts or doesn't predict success. I definitely do onabotulinumtoxin patients who have failed sacral neuromodulation or even to supplement them. If they get a little bit of a result, you can put a couple of therapies together, and because they're two different strategies, you may get a synergistic... It's not really synergistic, but trying to tackle the problem with two different approaches. I don't think it doesn't work. I'm not sure that you would say doing onabotulinum after sacral neuromodulation is predictably going to fail or not fail. I think it's the same as if you started with that first and then went backwards to sacral neuromodulation.
Alan Wein: Do you think there's a future in using neuromodulation for neurogenic patients? Let's say from the simplest, like a post-stroke patient up to the most complicated, like a spinal-cord-injury patient?
Kathleen Kobashi: Yeah, I definitely do see that in the, for instance, the multiple sclerosis patients, a lot of whom are almost like idiopaths. We do use sacral neuromodulation in those patients. I do. I mean, it depends on the patient, where their disease or their lesion is. I definitely think it's worth a try. And the nice thing about it is you can do a PNE and test stimulation and see if it works before you put the permanent implantation in. I mean, there's all kinds of things in the space that are coming down the pipeline, like transcranial stimulation and that sort of thing. If you can really find functional areas of interest to target, I mean that work is being done as well. So just when you think somebody has thought of everything, somebody thinks of something else. So it's an exciting time.
Alan Wein: How long do you think it takes, let's say one of the implant... If you put in one of the implantable devices, does that work right away? Or is it like PTNS where you have to use it for a while before you see a clinical result?
Kathleen Kobashi: Well, I'm going to tell you anecdotally in my experience, which isn't tremendously extensive, but I have seen gradual increase in the improvement over time. I don't know if anybody knows exactly what that time point is. I don't think it'll take as long as... Well, the length of time is interesting, because they're getting continuous or more regular stimulation than the once a week and then the once a month sort of maintenance. So I think I'm hopeful, I'm cautiously optimistic that that may be the case, but we are seeing that patients have done well and they continue to improve with some time over six months kind of thing. We'll see them still continuing to improve.
Alan Wein: Do you think the regularity of stimulation with the implantable devices makes a difference? Obviously there's a difference between eCoin and let's say BlueWind.
Kathleen Kobashi: Yeah. Yeah. I mean, all of those are excellent questions and remain to be seen. I mean, if we kind of extrapolate from the sacral neuromodulation data, we've all seen those patients who do really well initially, and then we just can't hit the holy grail again for whatever reason. And I don't know if it's a matter of millimeters or if it's a matter of tachyphylaxis type of a thing, I think there's a lot we just don't know yet.
Alan Wein: Right. Well, thank you so much for your time today. And thanks for the presentation and the answers to some questions, some of which have answers and some of which remain to be seen, as you say. So we'll look forward to further development for minimally invasive therapies for OAB. So thanks so much, and we'll see you at the next meeting.
Kathleen Kobashi: Absolutely. Thank you so much for including me here. Bye-bye.