Ladies and gentlemen, the program is about to begin. At this time, it is my pleasure to turn the program over to your host, Pavan Patel .
Great, thanks. I'll just give a quick introduction, given this is my first time hosting Supernus. Since I initiated coverage on October 29, I've been working for Jason Gerberry at Bank of America for close to five years now, focused on companies like Jazz, Horizon Therapeutics, Teva, Tarsus, and United Therapeutics, just to name a few. I chose Supernus as my first company to cover as lead analyst because I think it's a company that's undergone an impressive transformation to being a diversified CNS growth company. I think Jack's a solid operator with a strong track record. With that, I'm joined by Jack Khattar, who is the Founder and CEO of Supernus Pharmaceuticals. And he started this company as a spin-out of Shire back in 2005, so 20-year anniversary, and turned it into an up to $3 billion enterprise value company.
We can get straight into the Q&A. So the company most recently did a BD deal for the acquisition of Sage. And now that we're a full quarter into the Sage integration, can you provide some more granularity on the realization of the $200 million in annualized synergies? And are these savings coming mostly from SG&A? And have you done the work in order to go through the R&D programs and figure out what's going to be eliminated versus what you're considering continued development in?
Yeah, sure. And good morning, and thanks for having me. Really appreciate it. And I'll just remind first everyone that I'll be making forward-looking statements. So please check our SEC filings for all the risk factors associated with the business. So yes, I mean, regarding the Sage acquisition, the integration has gone actually very well, as well as we expected it, even a little bit better, maybe a little bit ahead from tracking the synergies to your question. And actually, in the last quarter, which we talked about in November, you can tell that SG&A, which is related to the Sage acquisition, was running about $14 million -$15 million a month, so to speak. W e've really brought it down significantly from the time when Sage was operating on an independent basis. And that is very consistent with what we announced back in August when we closed the deal.
We did say for the rest of 2025, which was at that time five months, about $70 million will be related to the Sage acquisition. So on a monthly basis, it's in the $14 million -$15 million. So yes, by the time we own the business for a full 12 months on an annual run rate, so to speak, in the first year, we should be closing in on the target that we put up for ourselves, which is up to $200 million on an annual basis. Yeah. And as far as to where these synergies are coming from, I mean, a significant portion is clearly on the R&D side. So from a program perspective, we've really been examining and evaluating the Sage programs before we continue with anything specific or restart any specific program. W e've been going through that process as we speak, and we've made significant progress.
Very exciting early-stage stuff that Sage has done over the years. So a pretty strong number of molecules, library of molecules, different platforms, some of which have been talked about publicly, other things that haven't been talked or disclosed publicly. W e're evaluating that within the context of our own discovery. As some of you may know, we've had now for several years our own discovery program at Supernus. W e're looking now at the whole portfolio holistically, regardless of where the program is coming from, and prioritize where our investment should be in the long term. So that's where we are right now, and we're really very optimistic as to how the integration has been going. The achievement of the synergies as time goes on clearly have been very, very much in line with what we expected.
And then with regards to the lead asset, ZURZUVAE, I think historically there might have been sometimes periodic disconnect between script demand and then the reported revenue due to inventory dynamics. So maybe if you could just help us understand how this evolved in 3Q and how you expect this to evolve moving forward?
Yeah, I mean, our understanding since we took ownership of the business and a little bit before that, of course, not much as far as inventory fluctuations that is significant in one way or one direction versus the other. We did notice that in the third quarter, actually, IMS or IQVIA restated their numbers. So there must have been some disruption in the trends on the prescription side. I mean, this is a specialty, obviously, situation, specialty pharmacy situation. So it's very unlikely that you're going to see specialty pharmacy stocking up unnecessarily unless it's in response to demand because these are high-ticket items as far as the drug and so forth. A lot of the growth, most of the growth is really demand-driven.
We've been very encouraged in seeing now almost three quarters in a row or four quarters in a row since fourth quarter 2024, seeing a sequential growth of about 19%-20% growth in the business. That is very healthy. Some of that growth is really due also to the fact that we've expanded the sales force ourselves as well as our partner Biogen. That expansion happened in the fourth quarter of last year into the first quarter of this year. Now you're starting to see the benefit of that expansion and really getting real demand growth behind the business. All in all, very strong start for the product, a very young product. I mean, it's only been a couple of years into it. It's certainly a very young product.
Haven't really scratched the surface as far as the demand because you're looking at about 500,000 women every year experiencing symptoms of postpartum, and only maybe, maybe half of them or 45%-50% get diagnosed and somewhere in the 60%-70% get treated, so there is a lot there to be done from an education perspective, both to the patients, women overall, as well as physicians, specifically OB-GYNs, in allowing them and helping them screen for the disease, diagnose it, and be comfortable in treating something like depression, which is something, of course, they're not trained to, right? As an OB-GYN, you're not necessarily trained to treat depression, but this is something you encounter and are encountering on a day-to-day basis, so we try to give you the ammunition, the tools to be able to assess, screen, and diagnose, and eventually treat that condition.
And then I guess just on the point about the upsizing of the sales force, can you help us understand the magnitude of that and how you see that in a steady-state scenario? And then what specialties are these sales reps targeting? Is it just the OB-GYNs, or are there other sort of specialties that are new sources of patient adds?
Yeah. The size of the sales force hasn't been disclosed publicly by Sage or Biogen. I'll keep that for now as is. But I mean, this is a specialty area. So you have 20,000-22,000 OB-GYNs. So it's not like it's a significantly huge sales force, so to speak. It's in line with what you would expect a specialty sales force to be in. Given the most recent expansion clearly that I just talked about, I mean, typically the way we do it, and this is something, of course, that will be discussed with Biogen as time goes on, whether there is a need for further expansion or not. Typically, at Supernus, what we do is more like a stepwise approach. We don't jump in, throw hundreds of people at a situation and hope it pays out from an investment perspective.
We clearly like to see a return on at least the current expansion and see how that is and be able to measure it well through very well-established metrics. And then that should allow us to have a much more informed decision on whether to expand any further in that space. Excuse me. As far as targeting and the physician audience we're reaching, the majority of it is OB-GYNs. And if you look at ZURZUVAE's prescriptions today, since launch, it's been mainly in the OB-GYN space coming from OB-GYNs. About 80%, give or take, of these prescriptions are coming from that physician audience. The remaining 20% is from psychiatrists. So it typically depends on, of course, the patient, how they come into the equation, so to speak.
Are they being referred to a psychiatrist, or are they being referred to an OB-GYN, or they are picked up by the OB-GYN through the screening and the diagnosis done by the OB-GYN? But that's where the landscape is at this point.
And then I guess you mentioned that it's mostly demand-driven. So in terms of the growth scenario, should we expect that to be steady from here, or are you expecting them to evolve as payer coverage expands? Or is payer coverage already at a steady-state level, and it should be just steady from here?
I mean, a significant portion of driving the demand will continue to be building the market. I mean, we are building the market at the same time launching this product. There's a lot of market building that is happening and will continue to happen because awareness around the disease, education around the disease is not really that well spread out and well understood, and I'm talking about even women patients themselves. Actually, about 80% of women who are diagnosed with postpartum is the first time ever they've even heard about it. They've never heard about the condition before that. So there is a lot of education that has to occur among women and clearly then among the physicians who are going to encounter that condition and how to look for it and how to screen for it, diagnose it, treat it, and so forth.
A lot of the demand is going to be driven by grassroots activities, building the market, and growing that demand throughout. So again, back on my previous point, I mean, 500,000 women every year experience this condition. The product hasn't even scratched the surface as far as getting penetration into that market. And we're still really in the very early, early innings on this product.
And so of that 500,000 women per year who have PPD symptoms, what percent would you say are currently diagnosed? And how do you see that diagnosis rate improving over the next 12-18 months?
Yeah. I mean, diagnosis is estimated in the 45%-50%. It fluctuates, of course, every time you look at it, but it's in that range as far as diagnosis. And then treatment is more close to the 60%-70%. So there is still a lot to be done to really raise awareness, education, and then, of course, diagnosing these patients.
Okay. Great. Maybe we can switch over to Qelbree next, which is the largest asset for the company by revenue, and so I guess just going through the last 3Q results, I'm wondering, how did the pediatric segment perform relative to the adult segment? I know the adult segment is sort of framed as more of the untapped opportunity, right, so just wondering how we should think about that.
Yeah. I mean, we continue to grow very well in both segments. So back in 2021, we first launched the pediatric indication, and then a year later, we launched the adult indication. But the growth in pediatric, excuse me, continues to be very strong. And in the last back-to-school season, as we discussed at our earnings call, we grew by about 19% from a prescription perspective, very robust growth on the adult segment, although most of the emphasis and the inertia and the momentum has been in the back-to-school on the pediatric side, naturally, because of that importance of that season for the ADHD market. Despite that, we still continue to grow in the adult, and we grew by 32%. So growth continues to be very healthy and robust in both segments.
And we foresee that in the future as well because overall, when you look at Qelbree, based on the last month, for example, we had a high of 86,000 prescriptions in the most recent month from an IQVIA perspective. I mean, we're annualizing at 1 million, a little bit north of 1 million prescriptions a year. And this is a market that has 103 million or 105 million prescriptions a year. W e still have a long way to go as far as penetration of this market. And the market itself also continues to grow. So back to the back-to-school season, in Q3, the market itself on its own grew by 12% in prescriptions and has been on an annual basis year to date, it's around 9%. So very healthy growth even in the market.
And a lot of the growth is being fueled by the growth in the adult segment because historically, the pediatric segment enjoyed a very high level of diagnosis and treatment because we typically can diagnose a child or observe a child in school, at home. There are different areas where a child can be identified that they need help and so forth, not so much on the adult side. O ver the years, the adult segment is trying to catch up, so to speak, as far as level of diagnosis and treatment. And a lot of the growth has been fueled by the growth in the adult segment. And more and more adults, celebrities, and so forth, people are much more comfortable now talking about mental health in general and talking about ADHD and what they struggle with throughout their day.
The more people are outspoken, people relate to that. More people are coming forward looking for alternative treatments.
Just on this topic of growth drivers for Qelbree, maybe with the genericization of Vyvanse and ongoing shortages of various stimulants, have you seen an acceleration in switching to Qelbree, and is that still a tailwind to the business?
Yeah. I mean, the shortages and the stimulants, which we've seen now for a couple of years or more than a couple of years, actually, right after the COVID situation, doesn't necessarily help Qelbree, so to speak, unless it really persists and persists for a long time. And the reason I say that is if a physician makes a clinical medical decision that a patient needs a stimulant, they're not going to change the treatment just because the patient couldn't find that specific stimulant. There are a lot of formulations of different stimulants out there, a lot of amphetamine-based formulations, methylphenidate, and so forth, right? So more likely, they will go to another stimulant, at least initially, to get their prescription instead of completely switching the treatment paradigm from a stimulant to a non-stimulant just because of that shortage.
Some brands actually in the stimulant market have benefited from some of these shortages, but not so much Qelbree per se. Now, if a patient continues to hit a dead end, so to speak, and different stimulants are not able to get it and have that issue every once in a while, maybe a physician might reconsider at that time, "Look, maybe it's time for us to look for something else." But that's typically the dynamic that we have seen and that we would expect to continue if these shortages continue. Now, this situation has tempered down a little bit, so they're not as severe as they used to be, some of these shortages. So the situation has resolved itself in a way.
And then I guess in terms of the current source of business, in terms of switch patients versus treatment-naïve patients, for Qelbree, what's the mix for that look like, and has that shifted in the past quarter at all?
Yeah. It's been fairly stable. I mean, it ramped up, obviously, from the time we launched, but we are and have been around 30%-35% is actually first-line treatment- naive patients, which has been very encouraging versus what a lot of people expected initially when we first launched the product. They didn't know what to expect. Qelbree has been able to establish itself as a first-line treatment for a good portion of the patients. The other 65%-70% come from either an add-on or switches. And the majority of the switches right now, about half of them are coming from atomoxetine, which is Strattera, and then a good portion from stimulants, in the +30% from stimulants, which is very encouraging because a lot of people for a long time thought that Qelbree will only compete in the non-stimulant segment, and that has not been the case.
We've been able to bring in a lot of stimulant users who are dissatisfied with existing stimulant products for one reason or another. I mean, efficacy, people forget not all stimulants work for all patients. Also, a lot of, of course, issues with the stimulants on the side effects side and so forth. So a lot of these dissatisfied patients have considered and continue to consider other options such as Qelbree, and we continue to see that. I mean, there's a very healthy source of business coming from the stimulant side that is feeding into the Qelbree patient population.
I guess in terms of if you were to break down the two patient categories as non-stimulants and stimulants, what are the key reasons that patients on other non-stimulants might switch over to Qelbree? And then the same question for stimulants. I guess some of the feedback that we've gotten from KOLs is the adults, they'll go on these stimulants because they need a higher efficacy benefit, but then they get that afternoon crash, right? And then for non-stimulants, I guess just if you could frame what the key differentiation is relative to other non-stimulants, which I guess the non-stimulant share of the market is small, so it's sort of an opportunity for them to grow the pie, but maybe there is also some share gains from switches from other non-stimulants too, so.
Yeah. Sure. The dynamics actually differ a little bit between a pediatric patient and adult patient. As you rightfully pointed out, there are specific reasons why a parent would put a child on a non-stimulant. One of the obvious ones, of course, they don't want to put them on controlled substances and the abuse potential, all these issues, side effects, and so forth. And therefore, you do see, of course, more non-stimulant usage within the pediatric population than within the adult population. And one of the big issues have been, and that's why the market is 90% stimulant and has been for a long time, not because people want to use stimulants all the time and love them, for some adults do for other reasons. It's because the current existing older non-stimulants didn't work. And that's why we always say Qelbree is very simple about Qelbree.
It's a non-stimulant that really works, and what we mean by that is it works as early as week one, so as a parent, you don't have to wait as you used to with Strattera, two, three, four, five, even we hear up to eight, nine weeks into the school year to find out whether the product actually would work for your child or not. I mean, that to me as a parent is like eternity into the school year struggling with suspension letters, bad report cards, issues from a social perspective where my kid is isolated, nobody want to socialize, be their friends, and so disruptive in class, all that. That's like eternity, and therefore, as a parent, as much as I don't like it, I'll call up the physician and say, "You know what? I just can't take this anymore.
I can't see my child struggling and continue to struggle. Put them on Adderall or put them on a stimulant," right? And that's why the market has been skewed so heavily towards stimulants because the current older non-stimulants don't really work and work that fast. With Qelbree, it's a very different situation. As early as week one, you'll know whether it's going to start working for your child or not. And most likely, it does because we've seen that clinically. We've seen it in the clinical studies, but also in the marketplace now for the last four or five years we've been in the market. Now, for adults, as you said, they have a longer day. They like their stimulants, and also, but they have in the afternoon, they have that crash perspective, and they tend to supplement with an immediate-release stimulant to finish up their day.
And a lot of them like the feeling on the immediate-release stimulant, whether it gives them a nice high, buzz, whatever. They just like that, adults. And therefore, when they are struggling with their stimulants, let's say side effects or they're not still getting the efficacy they're looking for, what physicians tend to do is reduce the dose of the stimulant over time so they don't have a withdrawal issue with adults. And also, they don't want to, in a way, upset their patients by taking them off the stimulants completely because patients like it. So they reduce the dose from 50 to 40 milligram, 30 milligram, 20, and so forth, and over time, take them out of the stimulant and in the meantime, adding Qelbree over time, titrating up with Qelbree.
We do see, for example, within the adult patient population, a lot of use as a combination use of Qelbree being added to the stimulant, and then eventually, the stimulant taken off the equation completely, and the patient stays on Qelbree. And what many patients are finding out actually with Qelbree, I get a 24-hour coverage. I don't need to supplement later in my day as I used to with the stimulants because my stimulant controlled-release stimulant only lasts me 12 hours or 14 hours, which is not enough for my full day of activity. Qelbree gives you a true 24-hour coverage. So now I'm down to only one medication with Qelbree, and I'm able to conduct my business without having to supplement later with another drug. So a lot of the usage there is in combination with Qelbree and with the stimulant.
Great. Maybe we can shift to APOKYN and GOCOVRI next. I think this is one of the key focus areas for investors, right, because this is a high-growth asset. And so with regards to supply, I think your commentary at recent broker conferences has been that the supplier, which is used by STADA, has dedicated capacity for fill-finish for another product, right, which limits APOKYN supply. So maybe can you, one, help us understand the decision-making process from the supplier here? And then I have a follow-up to that as well.
Yeah. I mean, where we have been and where we are is that we have a current supplier, which is a third party, and the production line is not fully dedicated to APOKYN , so there are other clients on that production line. So capacity has been an issue from that perspective. And of course, our demand has been much higher than expected as well. W e've been, of course, pushing to get as many batches as possible from that production line. Now, at the same time, in parallel with that, we're exploring also an alternative supplier, which is actually our own current partner who markets the product in Europe and has been marketing the product in Europe for many, many years. They have their own production facility. W e're exploring that facility potentially to also produce APOKYN's exact same product, same cartridge that is being done for the European market.
We have a couple of work streams in parallel that are happening at the same time to make sure we can come back on track and we can restart the process of initiating new patients as soon as possible. W e're very focused on both, getting as much supply as possible from the current supplier, clearly to continue to serve our current patients, of course, and be able to get back on adding new patients while at the same time exploring another supplier that could be registered through the FDA and get them online to give us. And that second supplier, our own partner, has a lot of capacity. So from a long-term perspective, that would be a great solution anyway that we need. W e have a little bit more assurance, and we're not at the mercy of fluctuations from a capacity because of the third-party situation.
Yeah. I guess just a two-part follow-up. So first, I guess when I was looking through the EU regulatory filings, I noticed that the contract manufacturer there was Laboratoire Aguettant. I'm just wondering whether that's the EU manufacturer that's used in the apomorphine that's marketed in the EU historically and if that's sort of the opportunity with the second supplier. And then the second part of the question is, what's the timeline for filing a Prior Approval Supplement? Has that already been done? And what's the progress in terms of certifying an additional manufacturing facility?
Yeah. I mean, no, I'm not familiar with that CMO, so it's not the CMO we're talking about, the name you mentioned, and as far as timeline, specifically as to when and how quickly we can bring in that second supplier, I mean, typically, under normal traditional timelines, it could take you up to a year, actually, to file, produce few batches, create the data, make a submission to the FDA, give the FDA the chance to go and inspect the facility and approve the use of that supplier. Now, having said that, we're exploring with the FDA any other ways potentially we could expedite that process given the shortage situation we're in and the importance of not, of course, disrupting patients on therapy who are already on therapy on apomorphine.
We're clearly exploring different alternatives, different angles coming at it from different angles so we can expedite the process both with the current supplier, as I mentioned, but also with the new supplier that we can shorten that timeline. Absolutely, that's what we're doing and trying to do, I should say. So that remains to be seen as we continue our discussions with the FDA. But clearly, there will have to be certain submission, potentially inspection by the FDA of that facility. I mean, that facility produces according to European standards and so forth. And sometimes FDA may accept interchangeable inspection, whatever. I mean, there are different ways we're exploring what can be done here to get the product soon because it's exactly the same product. It's the exact same product that is produced in Europe as the product we have here in the U.S..
It just has to be released according to U.S. specifications instead of European specifications, and the FDA has to be comfortable with the facility at which it is being produced.
The current manufacturing facility, that's U.S.-based. Is that correct?
No, it is in Europe. So the facility is a European facility. So from a timing point of view, I mean, I wish I knew today it's a fluid situation as we continue to have multiple discussions, not just with the FDA, but also with the suppliers, as you might imagine. So definitely by February, when we give year-end results, guidance into 2026, explain to people what the guidance means, what does it mean to APOKYN , all that, clearly, will give more clarity and should be able to give more clarity by then as we get more information about both approaches in parallel as they are occurring at the same time. If we get information before that that is meaningful material, of course, we will communicate that before that.
Great. That's super helpful. So now that APOKYN has been on the market for a few months, can you share any details regarding the discontinuation rate?
It's fairly consistent with the clinical studies. We haven't seen anything that is unusual one way or the other. It's been very consistent with the clinical experience that we've seen in the study. Nothing really different.
Then are there any patients that are on the waiting list, which I think was 1,300 right at the Q3 results, who have decided to then go on to VYALEV instead? Is this a dynamic that you're tracking?
Yeah. I mean, that is a little difficult to track and find out. I mean, we certainly have a lot of forms that have been submitted, and actually, physicians continue to submit forms, interestingly. W e have a lot of forms. We have a lot of things that have been processed. We have patients that are waiting to be initiated, but it will be hard for us to really tell whether a patient has decided to stop waiting and they're not patient enough anymore and they want to go to a different alternative. That I truly don't know, and it's hard to track that unless you go back to these patients and ask them whether they're still waiting or not, which is not something.
Once we go back on track and able to initiate these patients, obviously, we'll find out at that time whether some of these patients have fallen off or completely went on to another alternative. The great news so far, I mean, since we've disclosed all this, of course, and communicated to physicians, I mean, physicians have been great. They've been very supportive. They understand. Of course, we're all disappointed with the situation, so to speak, but they're like, "Look, we appreciate the transparency. We appreciate what Supernus is really doing here, putting patients first, taking care of their current patients. We get it. We're here for you when you come back and tell us you have enough inventory. We need this product. This is an alternative treatment. It's not available anywhere else, so to speak."
Yes, there are other pump or other alternatives, but APOKYN is not a levodopa-based product, and we need something else. So we need something different to treat the patients. W e'll be here when you come back, and we'll be very supportive. And that's why we've been very careful as to when we come back and what we communicate when we come back. We want to make sure we have the full confidence. When we tell physicians, "Okay, we're back to normal. Let's start putting as many patients as possible." We need to have assurance that will be it, and we don't have another hiccup on the supply side. So that's why we're taking our time, being a little bit patient with it to make sure we have as much confidence as possible with any timeline we may end up communicating eventually.
And then when you have the inventory on hand, I think the period of time that it was good for, I think, for the label is like 12 months, right? And then in the EU version, I think the product inventory is good for 24 months. So is this potentially a change to the label that you might explore to have the inventory be good for a longer period of time so that you can maybe stockpile more inventory in the future when the supply constraint is resolved? Or how should we think about further down the line remediations of supply chain resiliency?
Yeah. I mean, typically, and that happens with all of our products. You start with a certain expiration date, and as you collect data and we continue to collect data on all our products, we continue to extend or expand the expiration dating. So that's normal. That will happen with every product we have. And that's an effort we always have there to give us a lot more flexibility from a supply chain perspective, to give us more the ability to have safety stock that doesn't expire on you. Now, with APOKYN , we haven't had the issue of inventory sitting around because the demand has been so high. And we expected, hopefully, as we come back, we'll continue to be high. So the risk of having products sitting in the warehouse and expiring is probably very low.
But it doesn't mean, in parallel, of course, to your point, we will continue to work on extending the dating if we can.
And then I think you alluded to this earlier, that enrollment forms continue to be added. So maybe if you can just speak to the volume of those enrollment form adds, is the level of demand continuing to be maybe not as high as before but meaningful so that there is sort of a patient bolus that's still available when you resolve the supply constraint?
Yeah. I mean, it's certainly not at the same rate as it used to be from before, as you would expect. Some physicians may just wait a little bit and say, "Okay, let me see where the situation goes, and then I'll see whether I keep adding." But other physicians continue to put in the forms and put patients' names in the queue because they also know that it will take some time to adjudicate these forms and get them to a point where we are ready to initiate that patient. Sometimes it takes several weeks to get to that point. And therefore, they may still feel comfortable submitting these, hoping, of course, we will resolve the situation in weeks rather than in a lot of months. So it is happening. But yes, to your point, yes, it is at a lower rate than it was initially.
And the answer is yes, as far as patients who are waiting to be initiated. Yeah. I mean, once we come back, and we'll have to work at that situation to make sure it's very well managed, we will have a big push, a big bolus of patients who will be initiated because of the queue and the backup and the backlog that we have built over the last month or so. C learly, that is happening right now, where a lot of patients, and it's adding by the day, so to speak, are waiting to be initiated. So once we go back, we do expect to have a big push as far as initiating new patients.
And then in terms of the reimbursement, so for the patients that were on the drug at 3Q, I think it was 400 patients, what percentage of those were on paid drug versus free drug? And should we expect revenue recognition per patient to improve over time? Maybe this speaks to the evolving payer coverage of APOKYN , whether there's still work to be done there.
I mean, we've actually had a fairly good, reasonable situation from the beginning at launch. We have coverage, and we're able to get coverage on the commercial side and Medicare. W e haven't had any significant hurdles in getting the coverage for our patients. So that has been fairly smooth. Of course, that is something you always work on and continue to improve as time goes on. But we haven't had any significant hurdles on that aspect.
Then on GOCOVRI, I think this product continued to grow right in 3Q despite generic entry maybe for other amantadine products. So what's driving this durability? Is it the dyskinesia indication, or is it broader use in the OFF episodes?
Yeah. I mean, GOCOVRI, I mean, dyskinesia has been a major differentiator, of course, for GOCOVRI . It's the only product approved for both dyskinesia and OFF episodes. So more and more physicians are realizing they don't have necessarily to lower the dose of levodopa to get rid of the dyskinesia or avoid it, so to speak. They can continue to benefit from the levodopa dose and so forth and don't have to lower it and just add GOCOVRI . And if anything, not only it helps them with the dyskinesia, but also it even helps them further with the OFF episodes because even GOCOVRI itself treats OFF episodes as well. So more and more physicians are realizing that. And obviously, it's been an educational process because it's a paradigm shift in treating because physicians for so many years have been used to and have been trained. You keep raising the levodopa dose over time.
You hit dyskinesia, you start lowering the dose. And then you start adding all these other oral medications and so forth, and some of which even cause more dyskinesia. And we're like, "Doc, you don't have to do this. You can stick with the levodopa dose that you're at. You don't have to lower it. You can always look at adding GOCOVRI to help you with the dyskinesia." So it's been an ongoing process education-wise to really get more and more adoption of the product. And the product benefited, as we talked about it in the last couple of quarters, from the Medicare design. More and more patients have been hitting the low copay much earlier in the year versus later in the year. So that allowed us through the years to really keep more and more of our patients instead of losing them as we typically used to.
So that has helped a lot of patients to stay on GOCOVRI . And a lot of our patients have a copay of like $25 or less. So more of those have been able to get to that level earlier because of the Medicare redesign. So it's been really a great story that way. And we're monitoring it very closely to see how sustainable it is. And hopefully, it is that way.
Yep. Maybe we could shift to the pipeline in the last few minutes that we have here. So getting on SPN-820, I think you've had mixed results in TRD, and you've initiated a study in MDD. Maybe if you can speak to what gives you confidence in the mechanism of action for the broader MDD population.
Yeah. I mean, on SPN-820, we've had three studies. The first one, which was a Phase 1b that was done by the innovator, early proof of concept. It was one single dose of 2,400 milligrams. And they measured efficacy as early as two hours, four hours, and then up to 72 hours. And the drug separated from the placebo even on the HAM-D6. Back then, smallest study that was. Then we did an open-label study in MDD mimicking pretty much that dose but repeated the dose, not just one single dose, but repeated dose up to day 10. And we saw very similar efficacy, actually, on MADRS, very significant. Now it's open-label. Of course, the big caveat is an open-label study. At the same time, we had a Phase 2b study in TRD, but the dosing regimen was 1,600 milligrams every single day. So that failed.
We think it's all related to the dosing and the regimen that you're giving this product at. And we think this is a mechanism of action that you don't have to hit it every single day. So this is a target in CNS. And as other targets have been shown and more evidence has been emerging very recently, that not every target in CNS you have to engage every single day with a dose. And mTORC1 activation, we think you can hit it with one single dose, such as the 2,400 milligram, and you allow the system to actually benefit from that dose and let it reset for 48 more hours and so forth, and then hit it with a dose.
An intermittent dosing of 2,400 milligram, which is the newly designed Phase 2b study, which we're about to start before year-end, we think that has a great shot as answering that question. It will duplicate, actually, what we've seen in the open-label. I mean, we've seen that dose and that dosing regimen work in the open-label. Again, yes, it's open-label, but at least we have some data that shows us this is probably the way to go with this drug and the way the mTORC1 activation works in the body from a biological perspective. There are drugs like this. I mean, there are very well-established like ketamines, psychedelics, and so forth. You don't have to hit the system every single day with a single dose.
Okay. That's super helpful. And then moving to SPN-817, which I think will be the last question we're doing. We're coming up at time. You mentioned some open-label data for SPN-817 in the past as well. So maybe if you could provide some more color on the safety profile of this asset, particularly the adverse events that maybe you've seen in the maintenance phase.
Yeah. I mean, with 817, given the mechanism, it wasn't unexpected, really, the cholinergic side effects, specifically the nausea, the vomiting, some of the GI side effects. W e expected that. And we actually, in the open-label, we did instruct physicians to use antiemetics, but they didn't follow instructions as well as they should have. Or sometimes they did give an antiemetic, but it was a little bit too late. Patients already have either experienced nausea and dropped out. And that's why in the titration phase, we saw a high discontinuation rate of about 27%, if I'm not mistaken. But that discontinuation went down to around 7% or 9% in the maintenance. O nce a patient can go over the hump from a titration perspective and get to maintenance, we saw them they can build the tolerance and they can stay with the drug.
What we're doing right now in the Phase 2b study that is going on, it's not by choice, but it's obligatory to use antiemetic with the medication. W e are telling physicians, "It's not really a choice here. You have to use an antiemetic in the Phase 2b study." We're also exploring other mitigation strategies from a formulation perspective on the drug. W e will input that and amend the protocol on the Phase 2b as we learn from these other mitigation strategies as time goes on. But I mean, the product works really well. We've seen that in the open-label, but also we've seen it from patients who've been on the drug for more than just one year. W e know it's not a placebo effect, obviously. And also, it has a huge differentiation potential here because of the acetylcholinesterase inhibitor as a mechanism of action.
The potential pro-cognitive benefits here could be very important. As we all know, for epileptic patients, cognitive decline is one of the big issues they deal with. And if we can have a drug that not only is potent but also can give you some pro-cognitive benefits, that would be a huge win potentially for patients.
Great. Thank you so much for the time today. I really appreciate it.
Thank you. Bye-bye.
Bye-bye.