Now we're ready to get started. All right, welcome everyone. I'm Josh Schimmer from the Cantor Biotech Equity Research Team. Pleased to introduce the management team from Neurocrine Biosciences. We have Matt Abernethy, Chief Financial Officer, Todd Tushla, Vice President of Investor Relations, and Eric Benevich, Chief Commercial Officer, should be joining in just a moment. But a lot going on at Neurocrine. Matt, kind of give us a quick snapshot of the highlights of 2025 that we've passed and are yet to come.
Well, thanks, Josh. And we will be making forward-looking statements, so I'll get that out there. Yeah, happy to be here. A lot going on for Neurocrine, and hopefully this is Eric. We have an open chair here. A lot going on for Neurocrine. INGREZZA is going quite well. $2.5 billion in sales is what we expect this year. In addition, CRENESSITY. What about CRENESSITY, Josh? That's just been an incredible launch so far. First new medicine in over 70 years for patients with congenital adrenal hyperplasia. And that launch has got off to a really strong start so far. In addition, which goes a little bit under the radar, is that we have two major phase III programs that we've initiated. The first one is for osavampator for major depressive disorder. Three phase III studies ongoing, as well as an open label extension.
Then we also have the muscarinic program, where we have a schizophrenia trial ongoing and plan to initiate one in bipolar mania later this year. Those trials right now, or those programs, are off to a strong start. It's a little early to give an update on overall enrollment and where we expect. But I'd just say that so far, the teams have done an incredible job, and kudos to Jaskaran Singh and Samir Siddhanti for getting those both up and running. So momentum is a real thing. You can feel it inside of a company. We're busier than we ever have been, focusing on the expansion of the sales force with INGREZZA, the contracting that we've had going on, launching of CRENESSITY, as well as standing up these trials. So momentum is very good, and it's strong and on our side.
So the two pieces of feedback coming out of the second quarter call, which I'm sure Josh will spend a bit of time on here during the session. The first part of the dialogue with an investor is typically, "Wow, CRENESSITY is off to a strong start." And it's a pretty easy response, agreed, both on the enrollment form side as well as on the reimbursement side. It's been very nice to be a part of. The second line of questioning really comes down to INGREZZA and some of the contracting that we've entered into, the reasoning behind that, and how that ultimately plays into AUSTEDO's negotiation that they have ongoing with the government. So that's really the line of questioning.
We're in a unique position, and I'll leave you with this: two major medicines growing quite nicely, phase three trials that are up and running, and a strong financial position where we have a lot of flexibility for the years ahead. So Josh, I'll hand it back to you for some questions. And maybe for those who weren't at the dinner last night, we spent about two hours.
It was awesome.
And it was a really rich dinner. Any main takeaways for you or any areas you think we should?
Yeah, a lot to cover and probably too much for the short time here. But Eric, you walked us through the evolution of the contracting strategy for INGREZZA and then some of the nuances as we get into kind of the IRA decision for AUSTEDO. Maybe you can kind of give us that snapshot again because it's just incredibly helpful.
Sure. Yeah, so with INGREZZA, we're in year eight of the launch. And as Matt said, it's been a remarkable journey, and we're still experiencing double-digit growth for the brand. But we launched in 2017, and our approach has always been to contract selectively and to seek parity from an access perspective, whether that was parity on formulary or parity, in some cases, non-formulary. And actually, for the first few years of the launch, we didn't contract at all. It wasn't really until 2019 that we started to engage in contracts selectively. And what we found really starting last year, especially in the second half of 2024, was that being on formulary mattered more.
We saw that being non-formulary was having a bigger impact in terms of affecting patient starts and that payers were tightening up a little bit in terms of approving new patient starts and also reauthorizations for existing patients, and so we made the decision last year that we wanted to increase our formulary coverage in the Medicare segment, so there's a defined cycle for the Medicare formularies. Companies submit their bids towards the end of the year, typically in November or early December, and about 10 months later, normally they find out whether they were added to the formularies, and so late 2024, we submitted our bids for the 2026 formulary year with the goal of increasing our coverage from less than half of the Medicare TD market to somewhere north of that number.
What we found was that there were a couple of plans where we were non-formulary that came back to us after our bids were submitted, essentially saying, "Yes, we're open to adding you for 2026, but we're also open to accelerating that formulary addition into 2025." And so we were able to pull forward a major plan into 2025. And that implemented in April, so beginning of April, beginning of Q2, we bumped up our coverage from less than half to about 2/3 of the Medicare market for TD. And then again, there were a few plans that added us at the beginning of Q3. And so now we're north of 70% of the TD market in Medicare where we have coverage. And we have seen that this has started to benefit us in terms of reducing the friction associated with getting new patients started.
Certainly, we've been pleased with the volume growth. Q1 was a record quarter for us from a new patient start perspective, which is unusual. Typically, you don't see Q1 being a strong quarter for new patient starts because of all the reauthorization work you're doing, and then we saw Q2 was also a record quarter from a new patient start perspective, so I do think that the contracting work that we did to increase our coverage in Medicare has benefited us, although it's still early days yet. With one plan kicking in in Q2 and then a few more in Q3, we should continue to see the benefit of that in the second half of the year and into 2026.
So the net price impact from that decision was about 5% down for the year. But for us, it was a pretty easy trade-off to make to be able to accelerate getting patients onto therapy as quickly as possible. And one piece, just to clarify, because it's been a pretty common question for us, is what about 2026? And all of these contracts that Eric is referring to, those are fixed contracts that take us through 2026. So I feel like we're pretty well- positioned through the rest of this year as well as through 2026.
Josh, can I ask? Why, after eight years, did it start to matter whether or not we're changing?
Yeah, I think that so the question was, eight years into the launch, why does it matter now more than previously? Our sense is that payers are starting to manage specialty drugs more tightly than maybe they have in previous years. And I'm talking specifically about the Medicare segment, likely as sort of an outcome of the Inflation Reduction Act. And so I think everyone's aware that starting in 2025, payers have picked up a greater proportion of drug costs after patients move through the catastrophic phase. So they're on the hook for 60%, and manufacturers on the hook for 20% of the cost. And we saw some tightening up, as I said, of approvals in the second half of last year, as well as some plans that were changing their coverage criteria over the course of the year.
Net- net, it was getting a little bit harder to get new patients initiated. And so we felt like it was a worthwhile investment to increase our coverage and to reduce the headwinds associated with new patient starts. And it's translated so far into record new patient starts this year. But I want to say that our observation is not just in the VMAT2 market, but in general with specialty drugs, that things have gotten a little bit tighter in terms of coverage criteria and approvals sort of across the board in the Medicare business segment.
Anything we could do to take the sand out of the gears in this environment was something that was quite clear for us. Once we saw that sand getting added in in a more pronounced way and the friction for a prescriber, for example, to go through a coverage determination form process, it was much more difficult. And so for us, we're obviously wanting a new patient to go through the process as smooth as possible. But you also want the halo effect of a clinician when they think about the choice between INGREZZA and deuterated tetrabenazine, that ease of access isn't going to be a trade-off decision that they make.
How do we now incorporate the IRA and AUSTEDO in particular? Because this is now a multidimensional almost game of chess with all of these payers thinking about, first of all, as you're submitting bids ahead of the IRA final outcome, as you negotiate through it, as you're thinking about your installed group of patients, as you're thinking about new groups of patients that you may be considering. How do you think about navigating these next months of contracting negotiations?
Yeah. So I think everyone's aware that our competitor, AUSTEDO, is currently negotiating with CMS for their MFN price, which would be implemented in 2027. We don't know exactly when those wave two of drug negotiation prices are going to be announced. It'd be no later than the end of November, possibly earlier. But as you said, we are in the position of possibly having to submit our bids for 2027 Medicare formularies before we have any insight into the negotiation status of deuterated tetrabenazine. So ultimately, I think that we'd be speculating if we said that we had a good understanding of what the negotiated price is going to be. But ultimately, our strategy remains the same. We want to maximize access for the patients. We want to maximize patient share, which we have been doing so far historically and especially this year.
And certainly, we also want to make sure that we diversify our revenues. And so we see a long runway of growth potential for INGREZZA with exclusivity out to 2038, a lot of undiagnosed, untreated patients in the TD market. And then now, certainly with a second growth driver with CRENESSITY, having diversified revenue for the company, that's why we feel really good about where we are.
But it is multidimensional, and it's like game theory plus prisoner's dilemma all added together. And so we, of course, have a lot of different scenarios that we have mapped out. But all scenarios lead back to a few pieces. One is it benefits us significantly to get as many patients on therapy as possible. The second is what you alluded to. It has been very clearly seen over the last eight years that existing patients, on whether it's our product or deuterated tetrabenazine, plans have not been able to shift patients onto different medicines because of the underlying mental health condition of the patient. They're handled with a lot of care. So we do have confidence in the market, confidence in our product, confidence in some of these other dynamics. But we'll find out more here in November, and we'll continue to pivot as needed.
Do you look at the final outcome for AUSTEDO as essentially defining the eventual outcome for INGREZZA? That many years behind. Another important consideration that this price differential may just be temporary anyways.
So in the IRA, we qualify for the small biotech exemption. So in terms of what could our ultimate MFP be, there's actually a collar in terms of the range of potential discount that we might receive. And that range is between 25% and 34%. So we know our outcome to a certain extent in terms of what our MFP will likely be. We'd be selected in 2027. That price would become known at the end of 2027, and then it would be in place in 2029. But in between what gets announced in November and how things go between now and 2027 through 2029, I think that's the window of uncertainty that we're juggling. But Eric and team, I think, are doing a great job through this.
Is that the range for 2029 beyond, or I thought it changed in 2030?
It's pretty fixed in 2029 to 2034. There was one time, Josh, when it was presumed that there was going to be this sort of phase-in of what that negotiated price is. It looks like that negotiated price will be in effect immediately. However, there are some offsets, like the statutory rebate goes away, and you're guaranteed to be on all plans. So it is a multidimensional game of chess going on and hard to get your head around INGREZZA thinking about IRA. But if you just take a step back and think about a $2.5 billion medicine with a market where you have 9 out of 10 patients with tardive dyskinesia not being treated today, there's still a massive opportunity left to help many more patients with TD.
But on the flip side, we're also very thankful to have CRENESSITY and to also have our pipeline advancing the way that it is.
One last question on this, because I want to make sure we get it to CRENESSITY, just to make sure I'm understanding. Once you're through the IRA yourselves, does that mean you get 100% formulary coverage?
Yes, that's our understanding. And so just to kind of build on Matt's comment, we have a good degree of certainty for next year in terms of what our net pricing is going to look like and what our coverage looks like across all three segments, across Medicare, Medicaid, and commercial. It's when you get to 2027 where you do have a little bit of uncertainty around what that outcome looks like for our competitor and then how that potentially impacts INGREZZA. There's 15 drugs that are getting negotiated right now. And so this type of question is being asked really across all of those 15 categories. What happens with those medicines, and then what happens relative to coverage of the adjacent branded products in those categories? So we're not alone in this regard. But you've got about a two-year window where deuterated tetrabenazine has a negotiated price.
And then in 2029, we expect that we'll have a negotiated price implemented. And based on the regs, once you have an MFP negotiated price, you're supposed to be on all formularies of Medicare. That's part of the trade-off.
Yeah, there are a lot of nuances. Maybe to unpack another time, but I do want because it gets really interesting. Coming to CRENESSITY, though, we had a great discussion about the different kind of centers that you're targeting, the centers of excellence, the endo peds, the endo adults, and kind of the rapidity of which you can tap into these unmet needs. Maybe kind of frame that for us, the proportion, the numbers of each, and the progress you're making across those domains.
Yeah, I'll kind of walk you through sort of the nuts and bolts of the market for CRENESSITY. But I'll start off by saying that it's exceeded our expectations really from day one. We were very thankful that we had such strong data coming out of the pivotal trials in adults and pediatric patients. That translated into a really great label that we got in December of last year, especially in terms of having a broad indication for the treatment of classic CAH. We were planning for success, and we put teams in the field in the second half of last year, commercial and medical teams, to start preparing the market and to do disease state education and patient finding work that we think has really benefited us to be able to get off to a fast start once we did get approval in late December.
So ultimately, the way that we're looking at the market is that there's around 20,000 or so classic CAH patients in the U.S., we estimate. And this is ranging from infants all the way through to adults. They're under the care. Most of them are under the care of endocrinologists. And there's sort of three segments of endocrinologists that we're focused on. The pediatric endocrinologists care for that pediatric population, which is about 1/3 of the overall CAH population. There's around 1,100 of those out there. They tend to be more skilled in the art and comfortable managing CAH. They have more experience, and typically, they have patients currently with CAH. There's around 20 Centers of Excellence that are outpatient clinics that are affiliated with teaching hospitals generally. About half of them are accredited through the CARES Foundation, which is the patient advocacy group for CAH.
Those COEs, we believe, manage about 15% or so of the overall CAH population. Then the balance of patients, the majority of patients are cared for through adult outpatient endocrinology practices. So there's around 7,000 or so of those physicians out there. That's where you see a lower concentration of patients. Many of these adult endocrinologists don't have classic CAH patients in their practice. Or if they do, they might have one or two. In terms of how we've been segmenting the market and going after the opportunity, obviously focusing on the pediatric endocrinologists and the COEs. But we've also been educating and reaching out to those physician practices where it appears in the community they have CAH patients.
And so early on, first of all, the overall adoption has been more rapid than what we expected in the first quarter or two. And especially, I would say more referrals for treatment of adult patients coming from these outpatient endocrinology practices. So I would say that the adoption amongst pediatric patients by those ped endos and the referrals from those Centers of Excellence have been in line with our expectations. And the referrals from the community endocrinologists have maybe been a little bit ahead of what we expected. Ultimately, early on, the dynamic was about an equal number of adult patients being referred in relative to pediatric patients. As we've moved further through the launch, now two quarters plus in, we've seen it start to skew towards the younger patients and also more towards female patients, which is in line with what we've expected.
So we're ahead of where we plan to be at this stage. But the referrals each week have been very steady and consistent, and that's a good thing.
So you've defined the market as your estimate of the classic CAH patient population. Maybe talk a little bit about that dynamic between non-classic and classic and the potential to move into that non-classic setting and identify patients who would be suitable for CRENESSITY.
Yeah, so I just want to clarify, first of all, the indication is for classic CAH, and we have to be careful that we're promoting on label, but I think what you're getting at here is some physicians have a little bit of uncertainty around what's the boundary between classic and non-classic CAH, and part of what creates a little bit of a challenge from a patient-finding perspective is that there is no specific ICD-10 code for classic CAH. There's just a CAH code, and for every classic patient, there's three or four non-classic patients, and so you can think of CAH as sort of a spectrum disorder. On the one extreme with the most severe patients, essentially, they have zero enzyme activity, and they produce zero cortisol.
On the other end of the spectrum, with milder forms, the non-classic form, they may have some enzyme activity, and they may be able to produce some cortisol. Typically, those patients still take exogenous glucocorticoids, but maybe not at the kind of doses needed to suppress excess ACTH and androgen production. And so you've got sort of this range of enzyme activity and this range of cortisol production. And it's helping the providers understand sort of what constitutes classic. And certainly, everyone's able to appreciate if someone has CAH and they're a salt-wasting CAH patient, essentially, they're not producing any cortisol. In their mind's eye, that's a classic CAH patient for sure.
But we also enrolled patients that were not salt-wasting, that were simple virilizing patients that also had all the hallmarks in terms of not needing GC doses, not just to replace the missing cortisol, but super physiologic doses needed to suppress excess ACTH and androgen production. And so that's part of our educational effort is to help the physicians sort of appreciate what constitutes classic versus non-classic, who's eligible to be treated per label, and who it doesn't necessarily going to benefit from treatment. I think that this is a process that's going to be ongoing for a while.
Maybe a couple of more anecdotal comments, but this has been fun so far. In biotech, it gets hard. You have a lot of failure. You have the contracting, like we discussed for the first 10 minutes of this discussion, but to think about initiating a therapy for patients who have never had anything else other than taking very high-dose steroids for their life, this has been extremely rewarding. What we hear from patients, what we hear from clinicians, it's been quite fortunate, and Eric, being a commercial guy for the last 25, 30 years, he says, "I'm just waiting for the shoe to drop." The anecdotal feedback seems to be like the product's working, nothing new popping up on the safety side.
And so it's just been a really rewarding experience for all of us to launch a medicine that has a mechanism that Neurocrine was founded on 33 years ago. It's just a bright spot on many levels.
Turning to a couple of pipeline updates that we're looking for this year. First, Matt, we've talked about this. We've spoken to some cerebral palsy specialists who absolutely believe that VMAT2 inhibition is very beneficial for patients with dyskinetic cerebral palsy. And I came to you with such tremendous enthusiasm having heard of this, but you've kind of been talking me down around some of the expectations. How should we be looking at this next phase III data update for INGREZZA?
Yeah, it's clearly a high unmet need. You have a patient population, about 50,000 patients that have this choreiform movement associated with their cerebral palsy. And you would think, the hypothesis, because you've seen the choreiform movements in Huntington's disease improve, that it could help patients with cerebral palsy. Now, cerebral palsy is caused by prenatal trauma primarily. And you also have a trauma at delivery that makes this a very heterogeneous patient population. You also, on the clinical trial risk side of the equation, you have competitors who have failed studies in this space. And we borrowed the Huntington's disease chorea scale as an endpoint for these cerebral palsy patients. So there's obviously a lot of hope that we can help these patients with the new therapy, but there is a high level of clinical risk associated with it.
We'll see what the results look like later this year.
And then last, osavampator. We're going to get some of that phase II data disclosure, maybe a little bit ahead of what you had anticipated. What should we be looking for there? And to clarify, you identified two doses, but never identified which was correlated to which efficacy signal. So I think most have assumed that there's an inverse dose correlation. But I don't think you ever actually said that.
Yeah, we haven't disclosed what the dosing is or the dose response was in this trial. But what I can say is we saw a really clear response at one of the doses: p lacebo- adjusted MADRS score down 7.5 points, effect size near 0.7. So really just industry-leading efficacy results in our phase II trial. We've not published any of the information because through our partnership with Takeda at that time, we had not invested in any front-running of IP work that needed to be done. All of that, all the patents have been filed at this point. And so what you can expect out of that data set is you will see the different doses, what the responses were across a variety of different time points. And you'll also get a clearer view into what the side effect profile was.
I'm personally very excited about that medicine. It fits right into our existing sales channels' hands that are marketing tardive dyskinesia. It could be a big help through a different mechanism for patients with a major depressive disorder. Thanks, Josh.
Yeah, I think we're out of time. Thanks to the Neurocrine team. Thanks for joining us.
Thank you.