Anjali Kapur: Hi, thank you, Dr. Wein, for the opportunity to discuss this today. So as you were saying, there was a shift in the overactive bladder treatment algorithm in 2024 when the updated AUA and SUFU guidelines came out. Prior to 2024, we went through stepwise therapy with first behavioral, then pharmacotherapy in the form of anticholinergics or beta-3 agonists, and then third-line therapy. And typically physicians would recommend one after the other in this order. And in 2024, we really changed that treatment algorithm. So this allowed clinicians to offer minimally invasive therapies like Botox, PTNS, sacral neuromodulation, and the new implantable tibial nerve stimulation devices all upfront and really taking into account patients and shared decision-making and what their priorities were. So this really changed what we can offer for overactive bladder.
And I just want to talk about a little bit of background in terms of shifts of patient preferences. This was actually a study I did as a resident, basically looking at if patients would be interested in this new technology with implantable tibial nerve stimulation. And we did find that a lot of patients who had previously tried sacral neuromodulation or were interested in it actually would also be interested in something like implantable tibial nerve stimulation. And patients who did undergo PTNS also tended to switch to this therapy, likely because there's less burden in terms of using iTNS as a therapy compared to PTNS. And I'll talk about that in this next slide. So, in terms of tibial nerve stimulation, just as a background, the way that it works is that it originates from the L4 to S3 spinal roots. That allows us to cover a larger ground in terms of recruitment of the afferents that are responsible for bladder control. A larger ground in comparison to just the S3 nerve, which is stimulated by sacral neuromodulation.
And the responses that we look for when stimulating the tibial nerve are in terms of motor response; it's toe fanning or great toe flexion. And in terms of sensory response, it's plantar paresthesias on the medial or lateral plantar branches underneath the foot. So the issue that we found over several years with PTNS is that there is a very high dropout rate. Although patients in clinical trials have shown great adherence when they do weekly sessions for 12 weeks and then, once a month, are doing maintenance therapy, there's a 69% reduction in urge incontinence episodes per day, so we know that it works. However, looking at real world compliance, the number of patients who actually stick to the induction period of those weekly sessions every 12 weeks and the number of patients who remain on maintenance for about one year is much, much less than that, only about 30% to 40%. And so a lot of this is because there's a huge burden of visits that patients need to attend; office visits every week for 12 weeks. That can be difficult with schedules. There tends to be a drop in efficacy at about one year.
And sometimes it's just difficult in terms of insurance coverage if, after a year, patients may lapse in insurance and this may no longer be covered for them. So now we'll get into the landscape of implantable tibial nerve stimulation devices. There are currently three which are FDA approved and available and commercially used. The first one that came about was something called eCoin. The next one was Revi, and the next one was Altaviva in terms of the order in which they were FDA approved and available. They're grouped by their location in which they're implanted, which is either above or below the fascia that overlies the tibial nerve on the inner ankle. And eCoin and Altaviva are both above the fascia. Revi is considered below the fascia. In terms of the battery location for eCoin, it's considered internal, which is in the implant itself. It's a non-rechargeable primary cell. And the device is stated to last about three to six years before requiring replacement. The mode of delivery is automatic, so there's no patient action required in this.
Stimulation is delivered 30 minutes every three days and this is programmed. And typically activation is performed four weeks after healing, after the actual implant procedure, although this can anecdotally be a shorter period as well. In terms of Revi, it's implanted below the fascia. The way that stimulation is delivered is through a wearable device that patients place on their ankle sitting above where the implant is. And so that battery location is actually external, and the wearable device is rechargeable. So patients activate this therapy by wearing the wearable device around their ankle and therapy is suggested at 30 minutes at a time, one to two times daily. And again, with Altaviva, it's very similar to eCoin. However, the battery life lasts 10 to 15 years, and it's a rechargeable device, one to two times per year. There again is no patient action required. It's automatic stimulation, and this is suggested to occur 30 minutes three times per week. With this device, the difference is that same-day activation and delivery of therapy is possible.
Just a quick review of the efficacy that's been reported in the pivotal trials and one and two-year data for each of these devices. I'll say it is difficult to compare these studies head-to-head because they were each designed very differently and their definition and timeline of efficacy is different. But just an overall view, this is showing that at six and 12 months for each device, the efficacy, which was defined as greater than 50% reduction in urge incontinence episodes per day. The efficacy at six and 12 months ranges between 58% and 78% for all of these devices. And then at 24 months, again, the studies are difficult to compare head-to-head, but these were patients who were case completers, and we see that eCoin and Revi have very similar rates of efficacy, almost 80%, and Altaviva at 55%.
So now I'd like to go into some practical considerations for implantable tibial nerve stimulation. So in terms of coding for physicians, right now it is coded as a Category III code, which is a temporary code. And that requires physicians or their billers to crosswalk this Category III code to a Category I code, which is considered similar in physician time and effort. A lot of the commonly used codes are ones that are similar to those used for sacral neuromodulation listed here. There's also a need at this time to do this procedure in the hospital outpatient or ASC setting for reimbursement purposes, and this may change in the coming years when that Category III code becomes a permanent Category I code. Things that we need to consider as well are battery life and rechargeability. This is primarily in relation to Altaviva and eCoin. And patient factors play a huge role in determining if these therapies are appropriate.
So age and the expectation of the patient to engage in the therapy and deliver it themselves, versus allowing it to be automatically delivered matters quite a bit in the expectation of efficacy that they might find. We also need to consider their dexterity if patient engagement in therapy is involved, as well as compliance and cognition. So where does implantable tibial nerve stimulation fit in the treatment of overactive bladder? Well, patients who may have trouble adhering or complying with PTNS but had a good result, they might be great patients where this is a good fit for them. Patients who might be hesitant about the risk of incomplete bladder emptying or retention with Botox, this is also a good treatment option because it can be done under local anesthetic and doesn't involve that risk of retention.
Other patients who might be interested in sacral neuromodulation but are hesitant about potential revisions, this could be a good therapy for them as well. And really anyone who fails pharmacotherapy, this could be a very good option. Other patients that we might want to consider maybe not using this therapy in are just ones that the population has not been studied yet. So patients with concurrent fecal incontinence, just nocturia, dry OAB without incontinence or stress incontinence, as well as neurogenic bladder patients have not been studied in these trials. And potentially patients with needs for lower leg MRIs are... Although these devices are MRI conditional. And then patients who potentially want a trial like sacral neuromodulation offers with PNE, this may not be the right therapy for them.
So in summary, implantable tibial nerve stimulation is on a level playing field as a minimally invasive therapy for overactive bladder. Its efficacy and safety so far are promising in the short-term studies that have been published. There are several practical considerations that we need to think of when determining if this is an appropriate choice for patients. And we know that implantable tibial stimulation does expand access to therapy for patients who may not otherwise have been interested or been eligible for an overactive bladder therapy in the past.
Alan Wein: That's about the best, most comprehensive discussion of implantable tibial stimulators that I've ever heard.
Anjali Kapur: Thank you.
Alan Wein: So do you think there's a difference in implanting above the fascia or below the fascia?
Anjali Kapur: So, I think for urologists, it is really dependent on surgeon comfort. We've never really operated in the ankle before and so this is the first time we've been even remotely touching this area. So it is just dependent on... There's a different stimulation field for each device that they offer. So sometimes there's a theory that under the fascia is just closer to the nerve and therefore delivers better stimulation to the nerve. But the results are comparable even with the above the fascia device for eCoin, although those studies can't be directly compared.
Alan Wein: Do you think anybody will ever do a head-to-head between two of the three or maybe even all three?
Anjali Kapur: I hope so. That would be great. Our head-to-head studies in these devices are really lacking, but we definitely need one to show us which way to go or what we can offer people.
Alan Wein: I mean, if you look at the results, the Altaviva, for some reason, seems to have less efficacy by the current definition. I mean, is that just an artifact of the way the population was chosen or was there a difference between those patients and the patients that were in either the eCoin study or the Revi study? I mean...
Anjali Kapur: Yeah, so I believe with the Altaviva pivotal study, which was called TITAN 2, the main differences were in BMI was a little bit higher compared to the eCoin pivotal study. And the definition of overactive bladder in prior therapies was slightly stricter. So patients in the Altaviva trial had to have failed at least two overactive bladder medications before being eligible for the device, whereas those in the eCoin trial were at least one medication. So there's slight differences in terms of who was recruited and who was implanted. It's possible that maybe the population in Altaviva is slightly more refractory. But again, there's so many factors that are different, so it's hard to compare.
Alan Wein: Do people ever switch from one implantable to another, let's say, from eCoin to Revi or something like that or not? I mean, usually once and done.
Anjali Kapur: Yeah, not in the trials that I know of, and I myself haven't had any patients that have switched so far, so.
Alan Wein: Do any of these people have ankle problems afterwards? I mean, let's say if they're tennis players, basketball players, anything like that. Are there any people that you won't implant because of their... Either just non-professional or professional activities that they do?
Anjali Kapur: Sure. So some of the relative contraindications that we think about are just lower extremity edema, varicose veins. So I make it a point if I'm going to offer this therapy to really examine patient's ankles now when I see them in the office and see... You really want to avoid poor wound healing in these patients as well, because there's risk for infection. Some of the most common adverse effects that have been cited are implant site pain and sometimes cellulitis or edema and swelling and erythema around the area. So there's a lot of considerations in terms of if you do have a very active patient who bikes or swims or is running all the time. They do need to be careful about healing in that area to avoid any significant discomfort and potentially some time off from those activities if they chose to go with that therapy.
Alan Wein: So last question, do you think that there's a difference in efficacy between those three therapies and sacral neuromodulation?
Anjali Kapur: I would say they're similar from what I've seen anecdotally in my practice so far. It's really just a difference if patients are really implant curious, and they would like... I would say the difference is really in if patients are willing to accept an implant or not, that's the first hurdle. And then, when you talk between the two, it's really just determining they might be a better candidate for sacral neuromodulation if they have both fecal incontinence and urge incontinence-
Alan Wein: Right, yeah.
Anjali Kapur: ... because you're killing two birds with one stone. But if it's really just the urge incontinence, and they want a quick procedure under local because it's easy, and they want to see results sooner rather than potentially going through two steps, then they might be a better candidate for implantable.
Alan Wein: Yeah. Well listen, that was a terrific and very informative discussion. And I think anybody who watches it will come away with a much greater knowledge about the three technologies that you discussed and how they stack up not only against each other, but against sacral modulation and also where to put it in your particular algorithm for treating patients with overactive bladder. So really thank you so much because I thought that was terrific.
Anjali Kapur: Thank you. Thank you for having me.
Alan Wein: Yeah. You bet.