Neurocrine Biosciences - Earnings Call - Q3 2025
October 28, 2025
Transcript
Speaker 2
Today, everyone, and welcome to today's Neurocrine Biosciences Third Quarter 2025 Results Call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session. You may register to ask a question at any time by pressing star one on your telephone keypad. Please note this call is being recorded. I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Vice President of Investor Relations, Todd Tushla.
Speaker 16
Hi, everybody, and a very pleasant good afternoon to you wherever you may be. Welcome to Neurocrine Biosciences Third Quarter 2025 Earnings Call. I'm joined today by Kyle Gano, Chief Executive Officer, Matt Abernethy, Chief Financial Officer, Eric Benevich, Chief Commercial Officer, and Sanjay Keswani, Chief Medical Officer. During our call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. After prepared remarks, and as is our standard practice, we will try to address all your questions. With that, I turn the call over to Kyle.
Speaker 7
Thank you, Todd. Good afternoon, everyone. Our third quarter results reflect Neurocrine Biosciences' exceptional execution and the strength of our enterprise-wide momentum as we continue to deliver across our commercial, clinical, and operational objectives. From a commercial perspective, for INGREZZA, the recent investments to expand our sales force and improve patient access drove yet another record quarter for both new patient starts and total prescriptions, highlighting the persistent unmet need for patients with tardive dyskinesia and Huntington’s chorea. With CRENESSITY, the strong launch highlights its role as a first-in-class therapy, redefining the standard of care for patients with classic congenital adrenal hyperplasia, or CAH. While there is still much to learn, we are encouraged by the early response from the CAH community and the potential to make a lasting impact for patients.
Momentum for both INGREZZA and CRENESSITY is strong, and we believe continued targeted investments in these commercial assets will accelerate growth into 2026 and beyond. In our clinical portfolio, I am pleased with the steady enrollment progress in our Phase III studies of osavampator in major depressive disorder and Directlidine with schizophrenia. We remain on track to meet our enrollment objectives for the year. Beyond these late-stage programs, we continue to advance a robust early and mid-stage program that is expanding through high-quality preclinical programs emerging from Neurocrine Biosciences' internal discovery efforts. To this end, I'm also happy to report that we are on track to achieve our R&D productivity goals for the year, specifically four new Phase I study initiations and two new Phase II initiations.
Advancing two potentially standard-of-care changing medicines until their final phase of development, while simultaneously driving early and mid-stage innovation, represents a record level of productivity for us and positions Neurocrine Biosciences exceptionally well for the future. As I reflect on my more than 20 years at Neurocrine Biosciences and just over one year as CEO, I'm deeply proud of how far we've come. Yet, as we continue to evolve, I'm even more inspired by what lies ahead. Neurocrine Biosciences is poised into a new chapter of sustained long-term growth driven by our science, our people, and our unwavering commitment to the patients we serve and the veterans who support our mission. With that, I'll turn the call over to Matt.
Speaker 14
Thank you, Kyle, and good afternoon, everyone. The third quarter was strong across the board for Neurocrine Biosciences with $790 million in net product sales, reflecting 28% year-over-year growth, driven by continued progress both from CRENESSITY and INGREZZA. Congrats to all involved in the performance of these two medicines. CRENESSITY grew sequentially from $53 million in Q2 to $98 million in Q3, reflecting strong early adoption and persistency rates. In addition, 80% of dispensed prescriptions are now being reimbursed. Feedback from patients and KOLs remains quite favorable in terms of CRENESSITY's efficacy, safety, and tolerability profile. We look forward to continuing to add patients to therapy and to further establishing CRENESSITY as a standard-of-care treatment for patients with classic congenital adrenal hyperplasia (CAH). Momentum for INGREZZA also continues to build with our third consecutive quarter of record new patient additions in Q3, resulting in net sales of $687 million.
Of note, as you consider modeling Q4, the third quarter benefited from a 14th ordering week. Outside of this ordering dynamic, the combination of improved access and our sales force expansion are resulting in double-digit TRX growth, record NRX, and market share gains through the first nine months of the year. On the heels of this momentum and strength of the tardive dyskinesia (TD) market, we have decided to pursue an additional sales force expansion with three goals in mind. First, accelerate the development of the TD market between now and 2029, strengthening our position as we navigate the potential impacts of the Inflation Reduction Act (IRA). Second is to maximize INGREZZA patient share during this window of time. Third, set the foundation of an expanded psychiatry portfolio, anticipating one or more of our late-stage clinical programs will have successful top-line data in 2027.
From a financial perspective, the expanded investment in both INGREZZA and CRENESSITY will result in an SG&A expense increase of around $150 million in 2026. We will, of course, provide a fuller financial picture for Neurocrine Biosciences in February next year, but wanted to give you this insight for now. To close, our capital allocation priorities remain intact. Number one, drive revenue growth. Number two, advance our R&D programs. Number three, enable business development. Number four, return capital to shareholders. Our top-line growth and financial profile of over $2.1 billion in cash is the foundation for continued investment in our internal pipeline, which will position Neurocrine Biosciences for sustained growth and enable us to deliver new, innovative therapies to patients with unmet needs in the years ahead. With that, I'll now hand the call over to Eric Benevich, our Chief Commercial Officer. Eric.
Speaker 17
Thanks, Matt. Q3 was another banner quarter for our brands. Our commercial and medical teams continued to deliver with a record quarter for both INGREZZA and CRENESSITY, with combined net sales of $785 million. Starting with INGREZZA, performance through the first nine months of 2025 has been exceptional, reflecting both the strong clinical profile and the continued significant unmet need for people living with tardive dyskinesia or Huntington’s chorea. Past strategic investments to expand the sales force and improve access have been positive, yielding a third consecutive quarter of record new patient starts and total prescriptions. Today, of a population exceeding 800,000, we estimate only about half of those living with TD have received a diagnosis for their uncontrolled movements, and only about 10% are currently being treated with a VMAT2 inhibitor. With exclusivity out to 2038, there remains a significant organic growth opportunity ahead.
Our INGREZZA prescriber base continues to expand, particularly in psychiatry, where advanced practice providers such as nurse practitioners and physician associates now account for the majority of psychiatric patient care in the United States. As an example, our INGREZZA prescriber base is 30% larger today than it was two years ago at this time. In addition, TD prevalence continues to increase in conjunction with broader use of antipsychotic medications. In light of our strong momentum and the significant growth opportunity, we've made the decision to further scale up our INGREZZA sales force to meet this growing demand. Going forward, we will be expanding and restructuring our INGREZZA sales organization to create two dedicated teams: one combined neuropsych team and our existing long-term care team.
Both the neuropsych and LTC teams will be expanded to enable us to engage more VMAT2 prescribers than ever before and deepen relationships across our current base of prescribers. Consistent with prior expansions, success will be measured by growth in new patient starts and total prescriptions, metrics which typically show the full impact of field expansion several quarters after deployment. The expansion of the sales teams sets INGREZZA up well for 2026 and beyond and will also help position us for the anticipated launches of our next wave of investigational psychiatric medicines currently in Phase III development. Now, turning to CRENESSITY, our launch mantra of "So Far, So Great" remains well-deserved, with Q3 net sales reaching $98 million in just the third full quarter on the market.
During the third quarter, 540 new patients initiated therapy, bringing the total number of classic congenital adrenal hyperplasia patients on therapy since launch to more than 1,600. As we said from the outset, this is a new market we are building, and therefore, this is a learning launch. With CRENESSITY representing the first therapy developed and approved specifically for patients with classic congenital adrenal hyperplasia, we continue to gain important insights into prescriber behavior, patient dynamics, and potential seasonality trends. We continue to see steady adoption, and while the pace of new patient starts may vary from quarter to quarter, the strong persistence and adherence rates observed to date give us confidence in continued volume growth going forward. In the third quarter, patient demand modestly favored the pediatric population versus adults and skewed towards female patients.
Prescriptions continue to be written by a range of endocrinology providers, including those practicing in multidisciplinary centers of excellence, pediatric endocrinologists, and community-based adult endocrinologists. On the payer front, we continue to see strong reimbursement. Launched to date, nine out of ten people taking CRENESSITY have received approval through their insurance, and CRENESSITY is affordable, with nine out of ten people paying $10 or less per month out of pocket. Most pay zero. Insurance reimbursement has not been a barrier to treatment. As the first and only FDA-approved treatment specifically for classic congenital adrenal hyperplasia, CRENESSITY delivers a compelling combination of efficacy, safety, and tolerability. Our ongoing open-label extension studies continue to generate valuable data on quality of life, long-term safety, and differentiating outcomes, which will further strengthen an already robust data set. We estimate approximately 20,000 people in the U.S. live with classic congenital adrenal hyperplasia.
Based on the very favorable receptivity from the congenital adrenal hyperplasia community and the opportunity to bring relief to more people with congenital adrenal hyperplasia, we've made the decision to also expand our CRENESSITY sales team. As I said in my opening comments, we're executing very well from a commercial perspective. Both our products are fast-growing, innovative first-in-disease medicines. Given the significant growth potential for each, it was a straightforward decision to expand both the INGREZZA and CRENESSITY sales teams. This is an investment in growth and an investment in our future. Both sales team expansions will be fully completed by the end of Q1, and we can give further color on our progress as we get into 2026. These are very exciting times here at Neurocrine Biosciences as we make good on our promise to deliver brave science. With that, I'll hand the call over to Dr.
Sanjay Keswani, our Chief Medical Officer.
Speaker 1
Thanks, Eric, and good afternoon to everyone. My prepared remarks for today will be brief as we remain on track for all our clinical programs. We anticipate top-line results in the fourth quarter for valbenazine in dyskinetic cerebral palsy, as well as for the Phase II proof of concept and dose-finding study of NBI-770, that's our NR2B NAM, as an adjunctive treatment in major depressive disorder. As a reminder, positive results from NBI-770 could support a confirmatory Phase II study or the initiation of a Phase III trial in major depressive disorder. As Kyle mentioned earlier, the Phase III studies for osavampator in major depressive disorder and Directlidine, or NBI-568, in schizophrenia continue to enroll well, alongside solid progress for the rest of our early to mid-stage pipeline. You've heard us talk about our upcoming R&D Day throughout today's call.
As my colleagues alluded to, we are excited to welcome the Wall Street community to our San Diego campus, where we'll have an opportunity to provide greater detail into our long-term vision, much of which stems from enthusiasm around our clinical and early-stage programs, plans, and recent progress. To provide a bit more detail on the agenda, I will provide an overview of our neuropsychiatry programs with a spotlight on osavampator and our broad muscarinic agonist portfolio. Following my presentation, Dr. John Crystal, a leading psychiatrist from Yale University, will join me for a moderated Q&A session. Afterwards, Jude Onyia, our Chief Scientific Officer, will discuss Neurocrine Biosciences' ongoing R&D transformation efforts and preview a few of the next-generation programs expected to enter clinical development. We look forward to seeing many of you there as we unveil the foundation for Neurocrine Biosciences' next chapter.
With that, I will hand the call back to Kyle.
Thanks, Sanjay. I think we're ready to take questions now.
Speaker 2
Certainly. At this time, if you would like to ask a question, please press star one on your telephone keypad. You may remove yourself from the queue at any time by pressing star two. Once again, that is star one to ask a question. We'll take our first question from Phil Nadeau with TD Cowen. Your line is open. Please go ahead.
Good afternoon. Congratulations on a really strong quarter and great commercial performance. We wanted to just ask about the patient dynamics and patient starts for CRENESSITY. It did seem like enrollment forms were a little bit lower in Q3 than Q2. Was this seasonality or a sign of maybe an early launch bonus? I guess any insights you can give us on those trends would be helpful as we look to model the next several quarters of CRENESSITY. Thanks.
Speaker 17
Yeah, hi, Phil. This is Eric. Obviously, we're really pretty pleased with the overall adoption of CRENESSITY launched to date. With 540 new treatment forms in Q3, we saw that as a continuation of the strong adoption that we saw earlier in the year in the first half. We said at the beginning we expected this to be a steady or measured launch, and so far it really has borne out that way. The weekly adoption has been really consistent over the course of the summer. We don't think that there's necessarily any kind of quarterly dynamics going on or seasonality. We are still early in the launch, and we'll have to see how things bear out after we've gone through a few cycles. Ultimately, we're really pleased with the enrollment.
With over 1,600 treatment forms through Q3, we're really optimistic and expect to see this accumulation of patients as we go forward.
That's really helpful. Thank you.
Speaker 14
Phil, thanks for setting the tone also and asking just one question. For hygiene purposes, we'll stick to answering the first question that gets asked.
Speaker 17
Thanks, Matt.
Speaker 2
We will go next to Paul Mattes with Stifel.
Hey, thanks so much. Let me add my congrats on the quarter. I wanted to ask a question, I guess, about the IRA, and I hope you bear with me as it has two subparts to this. I swear to God, it's really only one question. Can you help us set up how you guys are thinking about the upcoming Oscado price that we'll learn about? What are the sort of implications for Neurocrine Biosciences? For INGREZZA, given the increased discounting and now that we're looking at a gross net that's getting up into the mid to high 30%, should we think that the worst-case scenario for you has now changed, given that the small biotech exemption taps the discounting to a level that is actually potentially going to be below where your gross net ends up? Thanks so much.
Speaker 14
Thanks, Paul. A lot to unpack there. Maybe I'll start with the first question and see how far we get on that. I think when it comes to Oscado, our view of this is that we'll learn of its pricing across both the current and immediate release and XR formulations in November. We should hear from CMS late November, if not sooner than that. That's what we're planning on currently. In terms of our expectations of how it might affect INGREZZA, I think where we stand right now is we're trying to understand what the plans might do in reaction to Oscado's pricing. Our view at this point is both the health plans and the PBMs will use a variety of strategies for medicines that go through the IRA, as well as those medicines that are not going through an IRA type of moment.
For us, there are things that we know and don't know. Ultimately, where we stand right now is that INGREZZA is an incredibly sticky medicine. Once patients start INGREZZA, they tend to stay on it, which really means we're looking at new patient starts during a two-year period of 2027 to 2029 when we reach our own IRA year. We'll look to contract here over the next, say, 12 to 14 months as we approach 2027. We'll look to maximize the number of patients that are on INGREZZA between now and the end of 2026. That will help us negate any headwinds on NRXs, which to date is only about 5% of our total TRX. On a quarterly basis, that number is quite small. We'll look also to see if there's any learnings from those medicines that are negotiated and become implemented next year.
I think most importantly here, we'll control what we can across INGREZZA, but across the portfolio, we'll look to build the company as strong as we can.
Speaker 17
Hey, Paul. This is Eric. I just want to chime in and reinforce a couple of points. One is that we do believe that there's room on formularies for MFP-adjacent products. We think that PBMs and health plans will behave differently. There is not going to be a uniform approach that they take. Tying in with our prepared remarks, it's really important that we maximize patient share going into 2027 and beyond. Currently, that's what we're doing, and that's part of the rationale for the sales force expansion for INGREZZA.
Speaker 2
We will take our next question from Tizine Ahmad with Bank of America.
Hi, guys. Good afternoon. Thanks for taking my question. Mine is going to be on CRENESSITY. Is it too early to know this, but are payers already looking for a certain level of steroid tapering in order to continue covering therapy? In terms of number of days in 3Q versus 4Q, we're heading into holiday season. How should we be thinking about the potential for seasonal impact for CRENESSITY sales in 4Q? Thanks.
Speaker 14
Thanks for the question, Tizine. This is Matt. We're not really anticipating seasonality outside of just the pace and cadence of patient visits into the clinician's office. Nothing on the seasonality front. In terms of reimbursement, it really has not been a requirement for patients to titrate down steroids to a specific extent. It's really looking at do they have the underlying disease and do they have treatment with hydrocortisone. If that's the case, reimbursement has been quite smooth. I'd just give a shout out to the team working on this, advocating on behalf of patients. I'd say the insurance providers can understand the benefit of this new medicine for these patients.
Speaker 2
We will go next to Akash Tawari with Jefferies.
Hi, this is Phoebe on for Akash. Thank you for taking our question. On INGREZZA, given that you've seen sort of Oscedo XR is already much more expensive than regular Oscedo, is there any changes in payer preferences you've seen thus far? In terms of the IRA negotiated pricing upcoming, how are you able to lock in INGREZZA's pricing through 2026 ahead of this announcement? Thank you.
Speaker 17
Thank you for the question. I think the health plans are seeing that part of what Teva is doing is trying to push patients to higher dose strengths of both the BID and the XR formulation of deuterated tetrabenazine. Since that product has a per milligram pricing structure, higher doses mean more revenue per patient. Health plans are catching on to that. We have seen examples of health plans that would, for example, cover the BID formulation, but not the XR. I think that the fact that we've seen this dose creep dynamic and/or patients transitioning to the XR formulation being more expensive to the plan, they've been more willing to engage with us. I think it partly explains the ability that we've had this year, mid-year, to expand our formulary coverage. The coverage that we have now, we expect to carry through 2026.
In terms of expectation setting for next year, we should expect at least the same level of formulary coverage that we have now.
Speaker 14
In most instances, we're seeing we're at parity from a formulary perspective. That's always been our goal, to take an approach to give clinicians a choice as to what medicine they prefer. That's going to be our strategy also going forward.
Got it. Thank you so much.
Speaker 2
We'll go next to Mohit Bansal with Wells Fargo.
Great. Thank you very much for taking my question. I would love to touch upon the 10-Q filing, and this talks about Department of Justice investigation. Any color you can provide on that? How should we think about the next timelines on this one? Thank you.
Speaker 7
Hi, Mohit. This is Kyle. I appreciate the question here on this. In August, we received a CID, a civil investigative demand from the Department of Justice (DOJ) requesting certain documents and information attached to the sales, marketing, and promotion of INGREZZA. Of course, we're fully cooperating with the DOJ. I think right now there's not much more to say on that. We'd certainly keep the external community updated when there's material information to share on that. The only piece I would conclude with is that we have an extremely robust compliance program here at Neurocrine Biosciences and we take compliance seriously and the responsibility that comes with that. As we move forward here, we'll continue business as usual because we think that's the right thing to do. Again, we'll keep folks updated as we learn more.
Thank you.
Speaker 2
We'll go next to Corey Kasimov with Evercore.
Hey, good afternoon, guys. Thanks for taking the question. Mine's on CRENESSITY. I guess I'm wondering if you can speak to where you are with getting CRENESSITY up and running at this point at the centers of excellence, and then the progress that's also being made in the community setting where docs see far fewer patients. Are you more or less at every COE at this point? Do you see that opportunity on the community level? Thank you.
Speaker 17
Yeah, and just to recap, we estimate there's around 20 centers of excellence out there that care for roughly 15% of the classic CAH patient community. All of the COEs have now started adopting, though I would say at different pace. I think that reflects sort of the different ways that they work, the level of bureaucracy, the level of access, etc. For the most part, our view is that the rate of adoption that we're seeing in the COEs is mostly a function of the rate at which patients are flowing through. We've also been surprised, very pleasantly surprised, I think, by the rate of adoption with community endocrinologists that treat the adults. Most of these practices, as you rightly call out, only have one or two patients.
That's where you get into a much wider pool of HCPs to reach, and tying back to our prepared comments as part of the rationale for expanding our field sales team to go a little bit deeper into our call universe and to be able to reach some of these practices that we haven't yet tapped into.
Very helpful. Thank you.
Speaker 2
will go next to Anupam Rama with JP Morgan.
Hey, guys. Thanks so much for taking the question and congrats on the quarter. Could you provide a little bit more color and maybe some quantification around the sales force expansion for both products in terms of the segments that are going to be targeted here for INGREZZA? Is it psychiatry, neurology, long-term, or for CRENESSITY? Is it general endos versus pediatric endos? Thanks so much, guys.
Speaker 17
Yeah, so in terms of scale, I would characterize it as about a 30% increase in terms of our overall sales footprint across both products. Obviously, INGREZZA is a bigger product, so most of the incremental headcount are going to be going to INGREZZA. I said in my prepared remarks that we were going to be both restructuring and expanding. What we're doing with INGREZZA is essentially combining our existing psychiatry and neurology teams and then expanding the headcount there. What we've seen is that we could do a better job, I think, of covering our psychiatry and neurology customers who in many ways are more similar than they are different by having a cohesive team versus having multiple different teams with different reporting structures. I think that this simplifies things substantially for us going forward.
We're going to keep the LTC team separate, and we are expanding that group as well. That's been a continuing fast-growing segment for us. We're excited about increasing our coverage of high-potential psych providers and neurology providers with the neuropsych team and then adding more headcount into LTC. The expansion with CRENESSITY is obviously smaller in scale. Our existing team is less than 50. This is going to be a relatively smaller expansion, but it does allow us to go deeper, especially in those community endocrinology practices and ultimately to accelerate adoption in classic congenital adrenal hyperplasia (CAH) and help more patients faster.
Speaker 14
This is really a reflection of our belief in the TD market and the opportunity that we have ahead. Eric's track record here, this is probably our fourth expansion. Every time we've done it, we've seen a tremendous response, and the team has done a great job driving more patients onto therapy. I would look at this investment as clearly being to accelerate the market development and to maximize the number of patients on therapy. We feel fortunate to have two great medicines to do this with.
Speaker 2
We will go next to Jay Olson with Oppenheimer.
Oh, hey, congrats on the quarter. We have a pipeline question related to Directlidine. As you look at potential indications beyond schizophrenia and bipolar, are you considering Alzheimer's psychosis? Are there any particular lessons you expect to learn from the Cobenfe Phase III study in Alzheimer's when that study reads out and any potential read across to Directlidine? Thank you.
Speaker 1
Thank you so much for the question. As you mentioned, with 568 or Directlidine, we're targeting our Phase III program, schizophrenia. We have initiated a Phase II bipolar mania study this year. We're also very interested in Alzheimer's psychosis. We do have a pretty robust muscarinic portfolio, and indeed, we'll unveil that at R&D Day in December. We have a lot of options in terms of which molecule we use, M1 preferring, M4 preferring, dual agonists for various indications. At the moment, we're thinking about AD psychosis for one of our follow-on molecules, which has particular advantages with respect to safety considerations in the elderly. We'll be watching BMS's Cobenfe data very closely. Our understanding is that their ADEPT Phase III study will be reading out relatively soon. There are going to be lessons learned, I think, for the whole field.
Great, thank you.
Speaker 2
We'll go next to David Amsellem with Piper Sandler.
Speaker 14
Hey, thanks. I wanted to come back to the sales force expansion for INGREZZA. You've had a number of sales force expansions over the years, over the commercial life of the product. With that in mind, at what point do you think the commercial organization is going to be right-sized? Also, at what point do you think the level of DTC spend is going to be right-sized? In other words, when do we start to see more aggressive margin expansion associated with the product? Thank you.
On the margin expansion, we've made tremendous progress over the last five years, being in the low 50% range all the way down to this year. We should be in the low 40% range. Growing revenue to almost $800 million this quarter is just a testament to the investments as well as the markets that we're playing in. When will we be 100% right-sized? You know we always invest as much as we can to pull as much revenue forward in any of these situations. We're learning a lot as we go with the TD market. Overall, from a margin expansion perspective, you know we look into the last part of this decade as being in a place where we'll continue to drive leverage, albeit maybe not as much as what had been anticipated in 2026.
It's really with an eye to maximize the number of patients on therapy heading into the 2027 to 2029 window.
Speaker 7
Maybe I'll just add there to that, you know I think we touched on this already, but the INGREZZA market as it relates to TD is an incredibly robust growth engine for the company. As much as we lean on the performance of the medicine, we're still only treating 10% of the 800,000 patients that are out there. That was with the backdrop of the TD prevalence continuing to increase at the rate of growth of the antipsychotics, which is 3% to 4% per year, which is 3% to 4 times greater than the general population. If you put all those pieces together, the number of prescribers increases year to year as well. It's increasing faster than we've expanded the sales force over the years. In fact, I believe the past two years, the prescriber base has increased by 30%.
As much as we have looked at ways of reaching all these patients and prescribers over time, the current structure of our sales organization is actually smaller than some of the companies out there with products just within schizophrenia. We like where we're headed to right now, but it's still an organization that is right-sized for tardive dyskinesia, not so much for some of these larger psychiatry indications. I think this is a step that not only helps us with INGREZZA, but as Eric Benevich said in his open remarks, sets the stage quite well for us as we look at osavampator and Directlidine in Phase III and their potential launch the second half of this decade.
Speaker 2
will go next to Brian Scorney with Baird.
Hey, guys. This is Luke on for Brian. On the upcoming 770 readout, can you talk about your expectations for the data? What type of result in your view would support a confirmatory Phase II as compared to moving right into pivotal?
Speaker 1
We're expecting the results of the Phase II study for NBI-770, that's on our NR2B NAM, this quarter. For context, the Phase II is a relatively small signal-finding study, with 72 patients total, with three active arms as well as placebo. The likelihood is that we would go into a confirmatory Phase IIB if the results we see are encouraging. We won't discount going to Phase III at this moment. In terms of what we'd like to see, we would like to see esketamine-like efficacy, not too dissimilar from Spravato, but without the baggage of some of the dissociative side effects, which mandate a two-hour in-house observation period post-dose. We'll see what we see later this quarter.
All right. Thank you.
Speaker 2
We'll go next to Brian Abrams with RBC Capital Markets.
Hey, guys. Congrats on the quarter. Thanks so much for taking my question. I was wondering if you could talk a little bit more about CRENESSITY persistence just now that you're several quarters in. Can you be any more specific in terms of what you're seeing there, and then just the overall KOL feedback around patients who started on the drug early in the launch and the glucocorticoid equilibration at this point now that patients have been on drug for many months? Thanks.
Speaker 17
Yeah, I mean, the way that I would characterize it is that CRENESSITY's persistence and compliance has been really strong. Certainly, we were hopeful going into the launch that we would see this kind of overall adherence to medication based on our experience in the double-blind studies and the open-label extensions. The vast majority of people that are starting treatment in the earlier parts of the year are still on treatment. In terms of the feedback on the reduction of GCs, obviously, you all have done your doc calls. You're probably hearing the same kind of thing that we're hearing. Patients are on treatment for a period of time. Doctors want to see how they can reduce the androgens, and then they start the process of tapering down the GCs.
It varies a little bit from provider to provider and also, I think, is dependent on the particular situation of the patient. Overall, we're seeing really good feedback in terms of both disease control with the androgen reductions and also the opportunity to really bring down those GCs to more physiologic or near physiologic levels.
Speaker 1
Thank you.
Speaker 2
will go next to Mark Goodman with Lyric Partners.
Yeah, Matt. At the beginning of the year, you were pretty conservative with respect to the CRENESSITY launch. I think your main issue, if I remember, was just reimbursement concerns and how quickly that would be adopted. Obviously, that's been adopted way better than anybody could have expected, I suppose. How do we think about gross tenets now? I mean, they clearly have come down a lot just working through the numbers. Are we continuing to move lower quite a bit outside of maybe the first quarter next year just because first quarters are normal, you know, unusual? If you think about the next three, four quarters, I think they're just going to continue to come down and ramp down to more normalized levels for what we, you know, consider a, you know, an orphan product like this. Thanks.
Speaker 14
Mark, that's quite fair. In terms of a guide for gross tenet, I would just characterize it as being less than a 20% gross tenet discount. That's something that in the foreseeable future, that's something we would be anticipating. Part of the gross tenet dynamics has to do with the nature of the patients. They're primarily commercial, but we also have a base of Medicaid patients, so you do pay the statutory rebate. Overall, the rate of reimbursement, as you mentioned, it's above 80%. As Eric said, 9 out of 10 patients have ultimately ended up with an adjudicated claim. I feel quite strong with where we're at and reaching a pretty darn good level in terms of how we think about the future.
Thanks.
Speaker 2
We'll go next to Sean Lamond with Morgan Stanley.
Speaker 1
Thank you. Hi, Kyle and team. Hope everyone's well. Maybe just circling back on INGREZZA, can you comment on neurology versus the psych split? Is it a focus on psych to the expense of neurology? I think I heard INGREZZA had a strong uptake in neurology, especially during COVID. What are your plans for neurology? Thanks.
Speaker 17
Yeah, neurology represents about 15% of our total volume. Obviously, all of the business segments, neurology, psychiatry, and LTC have been growing like gangbusters this year in particular. On a relative basis, it's now the smallest segment that we have. We view it as important, but it doesn't have the same kind of patient potential that we see in psychiatry. As I said in my prepared remarks, the fastest growing segment is really advanced practice providers that are in behavioral health. This reorganization and kind of combining our teams across psychiatry and neurology puts our resources where we see the highest growth potential. Behaviorally, the psychiatry segment and the neurology segment are more similar to each other than LTC. We're keeping LTC separate, expanding that team. We're combining our psych and neurology teams and then expanding that team.
Ultimately, we want to make sure that we can keep up with the pace of this market that's very fast growing and continue to drive new patient starts. This is an investment in growth, as we said, and we really like the trajectory that we're on now.
Speaker 7
Maybe just to add to that real quickly on the neuro piece, just keep in mind a lot of interest has come from the side of the CAH side of the indication opportunity with INGREZZA. For Huntington’s chorea, there are about 30,000 patients in the U.S. About 90% have CAH. That 20,000 number is about a 40 to 1 ratio to the tardive dyskinesia patients that we see out there today. I think that speaks to some of the volume flow that we see across the neuro and psych piece. That's something that we keep in mind as we look at further investments down the road.
Speaker 1
Thank you.
Speaker 2
We'll go next to Ygal Nochomovitz with Citi.
Hi, great. Thank you very much for taking the question. I had one on capital management. You mentioned, obviously, the increase in SG&A of about $150 million to expand both sales forces. With that in mind, I'm just curious, how are you thinking about the continuation of the buyback at the pace of that buyback related to the new $500 million buyback allocation? Thank you.
Speaker 14
Yeah, so we have $2.1 billion in cash right now, no debt. We're profitable. Where we're putting the capital right now is prioritizing top-line growth as well as investing in R&D at 35% is what our target range is. We, of course, have flexibility to do share buyback, but I would say that our bias is to utilize our capital for business development activities, right now focused on driving our own internal initiatives.
Thank you.
Speaker 2
We'll go next to Corinne Johnson with Goldman Sachs.
Yeah, good afternoon, guys. Maybe a question for us. Can you talk about where you stand with respect to share of kind of new-to-category or new-to-class patients with INGREZZA versus Osado? Where do you think that could go? Maybe contextualize that first, where we were a year ago and where you think we could go with the expanded sales force over kind of the next year. Thanks.
Speaker 17
Yeah, as Matt mentioned, new patient starts or NRX in any given week or month are single-digit % of total TRX. They're critically important because of the persistency and compliance that these patients have on INGREZZA, and they represent a significant number of likely refills. What we've seen really since the beginning of the year with the prior expansion of our field sales team and the investment that we've made in increasing formulary coverage, particularly in the Medicare segment, is that we're getting the majority of new patient starts. That's really what's driving increased total market share from a patient perspective. That's really an important part of our strategy going forward, this momentum that we're carrying through 2025 into 2026. We want to make sure that we continue that into that critical time period of 2027 and beyond.
The way I would look at it is we're gaining the majority of new patient starts now, and we intend to continue doing that going forward.
Thanks.
Speaker 2
We'll go next to Ash Verma with UBS.
Hi, thanks for taking our questions. I'm just trying to understand the medium-term growth outlook for INGREZZA given the sales force investment and the contracting that you've done. For the years before IRA impact, do you believe that you can grow at a higher pace versus where you guided to this year?
Speaker 1
I guess the way that I would characterize that is that this year, the VMAT2 market is experiencing double-digit growth, and our brand is growing faster than the market. We're really pleased with the growth trajectory that we're on. In fact, as we mentioned earlier, for Q3, that represented 12% year-over-year growth. The goal is to continue and carry that forward into 2026 and beyond and to maximize our patient share. We'll be able to give more color as we get closer to our Q4 earnings call and talk about the projections for 2026. At this point, it looks like we'll be able to see a continuing strong, robust, growing market for VMAT2s and INGREZZA in particular next year and beyond.
Speaker 2
We'll go next to Ami Saadia with Needham.
Hi, good afternoon. Thanks for taking my question. It's on NBI-770. Given that this study is not necessarily powered for statistical significance, just on an absolute basis, what is the level of change in the primary endpoint that you're looking to see as you think about some of the other drugs such as Spravato or other psychedelics in the space? Eventually, you know, are you thinking of studying this in PRD or NDD? Just sort of current thoughts. Thank you.
Speaker 1
Hi, Ami. Really, really good question. It's a relatively small study. I'm hesitant to give an effect size that, frankly, we would be considered as successful versus not because I think there's a huge amount of unmet need in this population. As you mentioned, there are potentially two populations that we could target with NBI-770. One is adjunctive treatment in major depressive disorder, which is currently where the program is headed. We clearly could go down this Spravato route with respect to treatment-resistant depression as well with this mechanism. We have a couple of options. We will decide that, I think, based on the data that we'll receive later this quarter.
Thank you.
Speaker 2
We'll go next to Samant Kulkarni with Canaccord.
Good afternoon. Thanks for taking my question. As the Inflation Reduction Act kicks in for your competitor, could you comment on where you might see the most impact on INGREZZA, either in terms of profile of patient or by prescriber type? On the neuropsych side specifically, what might be the maximum number of products that you might be able to leverage this iteration of your expanded neuropsych sales team?
Speaker 17
Yeah, let me take the second part of your question here. We'd love to have the challenge of having three products into psychiatry and long-term care at the same time. Obviously, we're really excited about the late-stage pipeline with both Directlidine and osavampator in Phase III trials. As Kyle said in his prepared remarks, data and potential launches later in the latter half of this decade. This expansion that we're in the midst of now, I think, sets us up well for being able to move and launch with either of those two products or potentially both. I would say that it's not sufficient, meaning, for example, if we end up having the opportunity to launch osavampator, we won't have the coverage of the primary care, future primary care prescribers that we would need to reach. This gets us partly the way there, but not fully.
I do think it reduces the amount of changes that we would have to make to prepare for either of those two launches down the road.
Speaker 14
In terms of impact from the IRA and the negotiation, our view is that patients or existing patients are ultimately going to stay on therapy during this window of time. You're thinking about a two-year window when you're dealing with new patients and where do they go. A lot of what we're doing right now is to maximize the number of patients on therapy between now and 2027. We're going to control every single thing that we can to maximize that number. We think we'll be successful during that window of time. We will learn more in terms of what the MFP is for osavampator as well as payer behavior over the coming months. For what we can control, we're doing everything we can possible. We have a great market with a great medicine here.
Speaker 2
We will go next to Yatin Suneja with Guggenheim.
Thank you for taking my question, Matt. One clarification, the 14-week dynamic or one extra week dynamic, that is just specific to INGREZZA. If you can just comment also on the inventory, if you can, for CRENESSITY. Thank you.
Speaker 14
Yeah, CRENESSITY inventory build was about $7 million for the quarter. As it relates to the 14-week, that does pertain to INGREZZA primarily. You can assume that was almost a full week of impact on the quarter. When you want to normalize Q3 to think about trajectory into Q4, I think it's safe to assume remove the week, and then you can grow off of that base from there.
Speaker 2
We will go next to Miles Mentor with William Blair.
Hi, thanks for taking the question. This one's just on CRENESSITY new starts. I think in the second quarter you added 664. You got 540 this quarter. Is there some sort of warehousing effect that's bleeding out of those patients? Can we expect that sort of trajectory for the next quarter and maybe a return to growth when you get that sales force expansion hitting in the new year? Thanks very much.
Speaker 17
Yeah, the way I would characterize the adoption in Q3 was that it was very consistent and steady. We said this would be a measured launch, and so far, it has played out that way. Although the overall rate of adoption, I think, since day one has been a little bit quicker than what we anticipated prior to the launch. We were helped out a little bit in Q2 by the wind-down of the adult open-label study, and there were some patients that transitioned towards the end of Q2 to a commercial drug that bumped up the numbers a little bit. Overall, I'd say that the rate of weekly enrollments has been pretty consistent across both Q2 and Q3.
Speaker 7
I'll just add here quickly, you know, the launch continues to exceed our expectations, and that's across the board: enrollment forms, persistence, compliance. That's played out here. Ultimately, as time moves along, the combination of the steady adoption of CRENESSITY as well as the persistency is going to stack volume over time and gives us all the confidence that we have and need for this to be our next blockbuster here.
Awesome. Thanks, guys.
Speaker 2
We'll go next to Danielle Brill with Truist.
Hey, guys. This is Alex on for Danielle. Thanks for taking the question. Another one on CRENESSITY. Just curious if you're seeing any new shifts in the new prescription breakdown between pediatrics and adults, and additionally any trends in the usage of the free drug program. Thanks.
Speaker 17
No, no major shifts from the demographic perspective. It still is skewing towards younger patients and primarily towards female patients. That pattern kind of kicked in after about a quarter or so on the market, and it's been pretty steady ever since. What was the second half of your question? I'm sorry.
Yeah.
Yeah, it actually continues to be less than what we had anticipated it would be. The idea being that if insurance hadn't approved the claim after about a week, we would be able to offer a month's supply of CRENESSITY to get someone started pretty quickly. As I mentioned earlier, 9 out of 10 patients that are on CRENESSITY have gotten their prescription approved through their insurance, so not that many people end up on the free drug program, to be honest with you.
All right. Thanks so much.
Speaker 2
We'll go next to Laura Chico with Wedbush Securities.
Good afternoon. Thanks very much. One of the pipelines with respect to valbenazine and dyskinetic cerebral palsy, the data coming up here, can you talk a little bit more about what would constitute a meaningful change in CRIA score in a CP population? Also, I guess, against the backdrop of the INGREZZA field force expansion, how should we think about the size of the opportunity and overlap with existing INGREZZA prescribers? Thank you.
Speaker 1
I'll do the first question really quickly. I'm going to head on for the second. This population, dyskinetic cerebral palsy, doesn't have an a priori validated scale. Essentially, we're borrowing from the UHDRS Huntington's scale. That's a total maximal CRIA scale. Our assumption is that a statistically significant effect in that would be meaningful enough. Clearly, we'll be seeing the totality of the data later this quarter.
Speaker 7
Maybe this is kind of just to add to next steps on this. We would take a data set, you know, if it was robust to the agency and ensure that there's a path forward for an NDA submission. With the current size and composition of the sales force, we would be covered there in case that was an SNDA.
Speaker 17
As I said, Terry, last thing I'll chime in here. The dyskinetic cerebral palsy population is larger than the Huntington’s chorea population, but still substantially smaller than the TD population. The expanded sales team, if this turned into an indication down the road, would be able to cover all the potential prescribers.
Thanks very much.
Speaker 2
We'll go next to David Huang with Deutsche Bank.
Hi there. Thanks for fitting me in and taking my question. Again, congrats on a strong quarter. I saw you have reiterated but not raised guidance. I guess you mentioned the extra week in Q3 for ordering. If we think about what the Q4 number may look like, I think the guidance implies something like down, you know, amid single digits to flattish. Anything else to think about in there in terms of maybe whether you envision seasonal dynamics or perhaps there's some degree of embedded conservatism?
Speaker 14
If you back out the 14th week, I think it gets you into a place to grow off of. Sequentially, what you've seen over the last handful of years is the fourth quarter typically will have a range of $15 to $20 million of sequential growth. My recommendation, David, is to normalize Q3 to a 13-week and then think about that type of a growth trajectory. Price should be pretty consistent. It was down 6% to 7% year over year in the third quarter. That should be something that you would experience in Q4 as well. Nothing abnormal on the pricing side.
Speaker 2
Our final question comes from Evan Seegerman with BMO Capital Markets.
Hi guys, thank you so much for taking my question. In your 10-K that was filed today, there was a disclosure about the Make America Healthy Again Commission issuing warning letters regarding DTC advertisements. You indicated that you got one for INGREZZA. Can you talk about what was in that letter and what you might need to correct, given that that is pretty important when it comes to the commercial plan for that asset? Thank you very much.
Speaker 7
I'll take this question. This is Kyle. I think many of us in the industry received a similar letter with similar types of contents in there. I think what a good view to have on this is as a pharma member, as we're committed to conducting responsible advertising for us, it is an important part of our business. We think it's a good opportunity for us to reach patients and also educate out there. We'll continue to look at that as an opportunity. Rest assured, we continue to do this in a responsible way. We'll look to continue doing that moving forward.
Speaker 2
This does conclude today's question and answer session. I will now turn the call over to Kyle Gano for any additional or closing remarks.
Speaker 7
Thank you. Thanks, everyone, for the good discussion and call this afternoon. Looking ahead, we're confident in the company's direction and momentum. We hope you can see here today that we're executing with clarity and discipline, expanding two commercial franchises in INGREZZA and CRENESSITY, advancing a robust and growing pipeline. We talked about some of our mid-to-late stage assets today and investing in the next generation of innovation. This is what Neurocrine Biosciences is about today and in the future. It goes without saying we look forward to meeting with many of you at the upcoming and remaining conferences this year and certainly at our R&D Day on December 16. Thanks again.
Speaker 2
This does conclude today's program. Thank you for your participation. You may disconnect at any time.