Retired senior biotech analyst at Jefferies. Thanks for joining us today. Next up is Supernus. To my left is Jack Khattar, CEO. Welcome, Jack.
Thank you. Thanks for having me.
Maybe a couple of minutes. Spend a couple of minutes talking about the Supernus story, any opening remarks you'd like to make, and maybe talk about your key priorities for 2025.
Yeah, sure. Good morning and thanks for joining us. Really appreciate it. Just quickly a reminder that I'll be making forward-looking statements, so please check the risk factors with our SEC filings. For those of you who may not be familiar with the name Supernus, we're a CNS-based company and focus on neurology and psychiatry. We have about seven products in the market. Our latest guidance is $630 million-$650 million as far as revenues. We are profitable. And we have a very exciting pipeline that this year we had tremendous news on both of our lead assets, one in depression and the other one in epilepsy. We've been going through a transition period right now because some of our legacy products are losing exclusivity.
We have a very exciting product in ADHD, a high-growth product that has been really carrying a lot of that burden and helping us make that transition as smooth as possible.
Wonderful. And Jack, in terms of the overall business, you've done a good job managing this. And so the question I have is, as we look forward into 2025, do you think 2025 total revenues could be a trough year before you return to growth? Because you've lost exclusivity, like you said, with Oxtellar, Trokendi, but Qelbree could possibly more than offset and you got other growth.
Yeah, I mean, 2025 will have the full impact on Oxtellar from a generic erosion perspective. So we'll see. I mean, we're in the midst of putting the 2025 plans right now and the budget and so forth. But we certainly are looking at Qelbree to continue to grow and grow very nicely and help us make up a lot of that shortfall. As well as we're going to hopefully also launch the pump, the infusion device in Parkinson's. The PDUFA date is February. Now that one from a revenue perspective may not be huge initially the first year because it's first year of launch and depending when exactly we launch it through 2025. But these will be some of the growth factors that will continue to help us manage that transition, and Qelbree has done significantly well, especially in the last couple of months, also with the back-to-school season.
We had a fairly strong back-to-school season. You can see that in the prescriptions, so we're very optimistic on Qelbree into 2025 as well.
Great. And maybe just one more question on the high-level part of your business is guidance 2025. You're in the midst of working through that. Do you plan to share specific product guidance for the full year? And there's another broker conference in January. Do you plan to give an update there or should we wait until Q4 EPS?
Normally we don't pre-announce early in the year. So the guidance we give typically in February is on the total portfolio. Now in the last couple of years, we've done guidance on the products that are about to lose exclusivity like Trokendi XR, Oxtellar XR to separate that at least from the rest of the business and try to show that actually we've been able and have managed very well to grow the business double-digit outside of these legacy products that are facing generic.
Yep, and so let's move on to Qelbree, your growth product. I think it's a $250 million run rate right now, and so one of the key questions is just how big can Qelbree get in your view in peak sales?
Yeah, the total market, ADHD market is about 93-94 million prescriptions on an annual basis, adult and pediatric, the whole, all the patient populations. By the time Qelbree peaks, we think the market easily will be 100+ million. Let's just use 100 for simple math, so to speak. And if we do a penetration of 3-5% and then a net price of we're now at $320 per prescription. By the time it peaks, it will be a little bit more than that. So it's a fairly simple math that we think this is a multi-hundred-million-dollar product. No question about it. It's a fairly big franchise. And as far as expiration, exclusivity, our IP goes all the way up to 2033, the latest to expire. So we feel pretty good about the product and its potential overall.
How has its uptake compared to other ADHD branded drug launches?
Yeah, I mean, we track all the launches, and if you look at the last decade or so and you synchronize the monthly aligned launches data, when you track that data, you'll see that Qelbree actually is one of the most successful launches. Despite the fact we actually launched right in the middle of COVID or a little bit after COVID in 2021, we were still dealing with physicians without access to them, telehealth, especially in psychiatry. A lot of physicians got used to not being in the office, so not much face-to-face with the salesforce and so forth. Despite that, we've had a very, very good run with Qelbree and we're still in the early innings, we believe. There's a lot to come as far as growth.
Got it. And I think consensus for this year is about 230, which is up from 140 in 2023. So as we think about 2025, maybe talk to us about how you think about sales growth because this year you benefited from volume as well as price. Can we get that same magnitude on both fronts in 2025?
Yeah, I mean, we certainly will continue to look for volume growth in 2025. No question about that given the comments we made about the potential. And as far as the price and the improvement in gross to net, we think we'll be in the 45%-50% range. Some of the one-time issues that were favorable for us this year won't repeat themselves typically, and they shouldn't repeat themselves next year. So aside from the typical fluctuations you have quarter to quarter from a gross to net perspective, there shouldn't be anything unusual there. And that's why the 45%-50% is a good range where we think 2025 will be in that region.
I see. And I should have asked is just high level, what is the differentiation of Qelbree to allow you to have this kind of sales trajectory so far?
Yeah, I mean, very simply, I mean, Qelbree, first of all, it's a non-stimulant. 90% of the market is stimulants, controlled substances, which we don't believe should be the case. Not every child needs the heavy hammer, so to speak, and the stimulant or controlled substances to control their ADHD symptoms. And especially when you have a non-stimulant that works. So I mean, that really what describes Qelbree. It's a non-stimulant that actually works. Historically, we've had a couple of non-stimulants. They work, they don't work, they don't work fast. A lot of shortcomings to them. Qelbree not only works, it works fast. Within as early as one week, you can tell whether it's going to really help the child or the adult. On the other hand, the non-stimulant has been around forever, atomoxetine.
Sometimes people wait six, seven, eight weeks into the school year and they still don't know whether it's going to work, and for me as a parent and my kid is really struggling in school, six, seven weeks is like eternity as far as the schoolwork, suspensions, social issues that these kids have to deal with, and therefore, Qelbree, whether it works within a week or not, is very important for the parents to make that decision and they can see whether the product is working. The second key differentiation is Qelbree works for 24 hours. It's a true once-a-day product versus a lot of the extended-release stimulants that today many adults have to supplement with an IR, immediate release later in the day to give them that full coverage.
A lot of these adults, when they make the switch to Qelbree, now all they need is one product that truly gives them that full 24-hour coverage. We're seeing a lot of combination therapy on Qelbree with stimulants where physicians will reduce the use of stimulant over time and introduce Qelbree to the therapy over time. Instead of discontinuing stimulants so quickly and could cause withdrawal to a lot of adults, they'll taper it off over time and then they introduce Qelbree over time and therefore eventually completely eliminate the use of the stimulants. That use is about 40% of adult usage right now of our prescriptions and adults are combination, interestingly.
I see. I see. And there aren't that many stimulants. I think there's only four non-stimulants currently. Although Axsome will have a non-stimulant phase 3 data, Q1 now, I think. And then I think Otsuka is also filing in 2025. So maybe talk about your views about potential emerging competition. Will that phase Qelbree?
Yeah, sure. Yeah, there are a couple of products, as you mentioned, one by Otsuka and the other one by Axsome potentially come in the market. As far as the timing of these products, we think the first one, the earliest that might come in probably if they do file next year, depending on when they file, another 10 months or 12 months for approval. So it's about a year, year and a half probably away. And then the Axsome product could be a little bit later than that. So clearly all depends on the label they get, the data they get, and how does it compare to Qelbree as far as potential advantages or disadvantages. A little bit hard for us to judge it right now.
Now, in general, extra noise in the non-stimulant market will not hurt to have somebody else who really pushes non-stimulants because, again, I'm a believer that the market should be the other way around, 90% non-stimulants and 10% stimulants, but it's actually the reverse, and there's a lot of work that can be done and help build that non-stimulant category and get away from controlled substances and potentially another crisis that's looming and waiting for it to happen.
Right. It's a big market too. Yeah. And so maybe let's move on to your pipeline because that is one of the narratives or the key stock drivers for 2025, let's call it. First one is your SPN-817 acetylcholinesterase inhibitors, SPN-817. You did share phase 2a data earlier this year, two different times actually, but maybe summarize for us what you saw and what compels you to move forward into a phase 2b.
Yeah, SPN-817 is a fairly potent acetylcholinesterase inhibitor. Now, as a class, that's not a novel class clearly, but it is a novel mechanism for the treatment of epilepsy or seizures in general. So we're the only ones developing that kind of class for seizures. And early on when we acquired the project, we saw a lot of preclinical data that showed that Huperzine A, which is the molecule for SPN-817, is really potent, is multiple-fold as far as efficacy and fairly predictable preclinical models, even compared to levetiracetam and some very well-known anticonvulsants. And that has been bearing out actually in some of the early human data that we've been sharing from the phase 2 study in the open label that you referenced. You're looking at seizure reduction in the 56%-66%, depending on whether it's maintenance period or post-maintenance period.
Now, I have to caveat that that's open-label clearly, so you have to take it on face value initially, but I'd rather have it this way than no effect clearly, and then when you look at the response rates, interestingly, very high response rates on this molecule, so people who can tolerate it, who can get to the maintenance period, they really benefit from it, and it's looking like the emerging clinical profile is pointing also more to more severe patients who tend to benefit from this molecule versus less severe patients. But that remains to be seen. Clearly, we need the phase 2b placebo-controlled study to give us more of a full picture, and we're looking at starting the study before year-end. The other important differentiation 817 could bring here is cognition, and acetylcholinesterase inhibitors are known and have been approved for the treatment of Alzheimer's.
Not that we're pursuing that at this point, but clearly cognition is very important in epilepsy and the treatment of seizures because these patients over the years, they start getting cognitive deficits because of the death of brain cells. Every seizure causes more cells to die in the brain and causes cognitive deficits. So a molecule that actually could help. And the initial data we saw in the open label is very encouraging. Using EpiTrack, which is a very validated instrument for cognition in epileptic patients, we saw about 75%-83% of patients either improved or were unchanged. Now, unchanged is actually a step ahead for these patients because typically they are on a decline. So if you have an unchanged cognitive measurement, that's actually a good thing. You don't have to have necessarily improvement, but even unchanged is a positive signal for the molecule.
So we're hopeful the differentiation will be on the potency, on the cognitive side. And then we have issues to deal with the tolerability because of the mechanism. Clearly, nausea, vomiting is a very well-known expected side effect for that class. And we're working pretty hard on different strategies to address that that we will incorporate in the phase 2b.
Makes sense. And as I think about what the phase 2b could show, should you improve tolerability and get more people to the three to four mg doses, which is very potent because you mentioned levetiracetam, Keppra. I mean, some of these epilepsy drugs are dosed in 500 mg or 1,000 mg a day. So it's potent. But going back to the phase 2b, placebo in epilepsy, my understanding tends to be 20%. And for clinical meaningfulness, maybe a 15% delta. So the point is you should have some room from what you saw in this phase 2b open label to the placebo control. Would you agree?
That's right. Yeah. I mean, it's a little bit more. Obviously it's neurology, not psychiatry. So placebo effect is a little bit lower. Although sometimes you do see higher placebo rates than that in some studies, but we think we have a lot of room versus the open-label. And we've had some patients actually on the drug for three, four years now, seizure-free. I mean, placebo doesn't last for three years or four years clearly. So the drug does work, no question about it, given the signal we have.
Okay. And could this phase 2b be a supporting pivotal if needed? Is that how you're designing it?
I mean, it's a fairly. It's not a small study. It's a sizable study. And therefore, yes, if the data is fairly clean cut as far as what it says and what it indicates, it potentially could be a supportive study in the registration package.
I see. And so it's starting up any day now. And when do we get data?
Data, I mean, epilepsy studies tend to be slow in enrollment. So data will probably be a year and a half from initial initiation of the study. I would estimate. Clearly, caveat all that with speed of recruitment and so forth. So we'll update folks as time goes on.
Sounds good. So things are pointing in the right direction. But moving on to your next program, 820, we will get data, phase 2b data, first half 2025, I think. And it's a novel mTORC inhibitor for TRD depression. I guess what did you see or what have you seen to give you that confidence that this is differentiated?
Yeah, way back, I mean, when we entered into the partnership with Navitor Pharmaceuticals, they had done a study, phase 1B, so just to give a little bit of background on that molecule. It was a placebo-controlled study, very small study, phase 1b initial proof of concept study. And with that study, they showed that a single dose of 2,400 milligrams of the drug works within hours. This is an oral treatment, just as a reference. It's not injection or anything like that. And they showed a very sizable effect size from the 0.4 all the way to 0.7, 0.8, which was sustained for three days with one single dose of 2,400 milligrams. That was on the HAM-D6 that was in TRD at that time. So we took on the program and the data that we just released is an open label study, very similar design.
It was a single dose, 2,400 milligrams, also per day, but we dosed it three times, so you got the dose on day one, then you got the dose on day four and then day seven. And we took measurements all the way to day 10. And we had significant, I mean, fairly very exciting data on reductions on both scales, MADRS and the HAM-D6. On MADRS, for example, it ranged from about 17-point reduction within hours in the first day and then went up to 23-point reduction on MADRS. And then the HAM-D6 likewise, I think it was like seven to nine or something like that as far as the reduction. And these are very extremely meaningful reductions. So of course, the big question is placebo is huge in depression, so this is open label.
Again, if I try to apply the same methodology or the same thinking that you applied on 817, for example, if I use on an average what the placebo is typically in MADRS, if you look at somebody published something about 23 placebo-controlled studies in depression, and I think the range was 5-15 or 5-17-point reduction typically. So even if you apply that range to our open label data, you still have very clinically meaningful improvement in MADRS. So very exciting molecule. Everything we measured, even on remission, within four hours of the first dose, again, this is oral, first dose within four hours, we had 35% of participants had remission on the MADRS, which is less than 10 points. And that went up to 63% by day 10.
And the response of 50% reduction or more, 50% of the participants, again, within hours of the first single dose and went up to 84% by day 10. So all the measures are very consistent, signaling what could be a very efficacious drug, very differentiated drug versus the marketplace, that's for sure. And also it showed cutting suicidal ideation by 80%. So safety tolerability, very nice profile for a CNS drug. So we're very excited about the profile overall and look forward to really get the phase 2b data first half next year.
I mean, first TRD, there's only what, Symbyax, Spravato. Secondly, it seems as if so far it's like a, you're showing like a psychedelic-like profile in terms of rapid effects and durable effects. You have a novel mechanism, but at the same time, you don't have like the hallucinations or anything. So this could be given at home.
Exactly. I mean, this can be given at home. There is no psychosis that we saw at all, dissociative effects, hallucinations, none of that. It's a typical oral product that you just take at home like every other oral product and you don't have to be in the clinic and under supervision and so forth.
Right.
Yeah.
Bar for success in the MADRS placebo-adjusted delta, what are you hoping to see in the TRD readout?
I mean, again, from a clinical point of view, six- to seven-point reduction is clinically meaningful, is considered as clinically meaningful. What I'm hoping is duplicating what we saw in the open label, hopefully, or anywhere close to that, that would be phenomenal.
Okay. Yep. And I think you previously said you would expect to complete enrollment in November. Have you done that yet?
We're either finished or about to finish the last patient. And because it's a 12-week treatment, so obviously we'll have to wait for the last patient to finish. And that's why data will be first half next year.
I see. I see. So if it's 12-week treatment plus, it is 12 weeks? Okay. 12 weeks, that's three months plus another month plus for data cleaning.
Yeah, data lock, cleanup, all that, and then analysis and reporting. So could we get it in the first quarter? I don't know. That could be a possibility. I'm not promising that right now until we go through it a little bit more.
I see.
But definitely in the first half.
Would you try to seek breakthrough designation on this?
That is a potential for it. Yeah. But we'll confirm that when we get it.
Okay. And let's just say this phase 2b did work. Does it count as a supporting pivotal study, meaning you would only need one more phase 3?
If the data is fairly meaningful and fairly clear cut, it's not like gray area clearly and pretty strong, that could be. Although I doubt it, but it could be. I mean, this is a completely first-in-class. So we may need to do two phase 3s anyway to get the number of patients up for the NDA package because this is a completely novel mechanism. So we may have to do that anyway.
Okay. Okay. And then the last couple of minutes left, I just want to talk about your other program, the apomorphine pump, which has a PDUFA February 1st. It has gotten a couple of CRLs, I believe. And AbbVie, you just got theirs approved after a couple or multiple CRLs.
It's a common theme, unfortunately, in infusion devices. Yes, CRLs.
And so how confident are you this time? Yeah, you can get this approved.
I mean, pretty confident. I mean, first of all, the list of issues we had to deal with was much less, obviously, than the first CRL or the second CRL. I lost track now with the product. So we feel pretty confident. The FDA has been active reviewing. And from the information request, the IRs we get, it looks benign at this point, meaning there are no concerns that we can tell or we should be worried about. So we're very hopeful that February comes. We should get approval, but remains to be seen clearly. And we're gearing up for the launch. I mean, we are happy actually that AbbVie did go through it. The FDA has let one of these pumps to go through the process and get approved.
And two companies in this space is actually not a bad thing because this is a completely new segment that we are creating and treating Parkinson's. It doesn't exist today in the U.S. It's existed in Europe for many years treating folks with infusion devices. Now we have a different drug than the AbbVie's product. Clearly, ours is apomorphine. AbbVie continues to be in the levodopa-carbidopa space. So we feel pretty confident about the potential here and a lot of room for two products clearly.
Yep. And the last question about this is you did mention maybe sales can be just relatively slower in the first year if this is approved. But what is your peak sales assumption in the U.S.?
I mean, the latest demand study, which we did, I think it was last year, we updated it, pointed to somewhere in the $200 million-$300 million. We only have U.S. rights. I know AbbVie talks about a $1 billion plus on a worldwide basis for their product. So there are some differences there. And maybe we are a little bit conservative, but that's okay. Let's prove it and show it to folks, and then we can increase the estimate.
Okay. Thanks for talking me through with all these updates. And look forward to all the progress over the next six to 12 months. And thanks everyone for listening in.
Thank you.