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Date
Wednesday, July 30, 2025 at 8:30 p.m. ET
Call participants
Chief Executive Officer — Kyle J. Gano
Chief Financial Officer — Matt Abernethy
Chief Commercial Officer — Eric Benevich
Chief Medical Officer — Sanjay Keswani
Former Chief Medical Officer and Strategic Adviser — Eiry Roberts
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Risks
INGREZZA pricing headwinds— CFO Abernethy stated, from a pricing perspective, expectations shifted from flat to approximately a 5% price decline for 2025, with headwinds more concentrated in the second half of 2025.
Gross-to-net impact on INGREZZA— Benevich noted, we saw an impact on our gross-to-net, which partially offset strong volume growth in Q2 2025.
Takeaways
Net product sales-- $682 million in net product sales, representing 17% year-over-year growth, as reported by Abernethy.
INGREZZA sales-- $624 million in INGREZZA sales, marking 15% sequential growth and 8% year-over-year growth, with record new patient starts for the second consecutive quarter.
Cranesiti sales-- $53 million in net product sales for Cranesiti, more than tripling from $15 million in the first quarter, supported by 664 new treatment forms in Q2 and over 1,000 received since launch.
Cranesiti reimbursement rate-- Over 75% of dispensed prescriptions were reimbursed.
Medicare formulary expansion-- INGREZZA now has approximately 70% formulary coverage of Medicare lives in the tardive dyskinesia market as of early Q3 2025, a 25% increase in coverage over Q2 and Q3 2025 through midyear rebate agreements.
Revised INGREZZA net sales guidance-- Updated INGREZZA net sales guidance range of $2.5 billion-$2.55 billion for 2025, reflecting double-digit volume gains and higher near-term gross-to-net reductions for INGREZZA.
SG&A expense guidance-- Increased by $25 million (GAAP and non-GAAP) to support ongoing commercial growth initiatives for Cranesiti and INGREZZA.
Cash position-- $1.8 billion in cash reported as of Q2 2025, supporting commercial and pipeline objectives.
Cranesiti adoption-- Prescriber base extends across pediatric endocrinologists, adult community endocrinologists, and multidisciplinary centers of excellence, with most physicians initiating treatment for only one or two patients so far in the launch.
Clinical pipeline progress-- Both osavampitor (MDD) and NBI-568 (schizophrenia) are enrolling in phase three registrational studies, with initial topline readouts anticipated in 2027 and later.
Phase one initiation-- First patient dosed for NBI-1435 in congenital adrenal hyperplasia; phase one study initiated in the prior month, described by Keswani as the first "investigational PET from our internal pipeline" to enter clinical development.
Inventory dynamic for Cranesiti-- Abernethy disclosed a $5 million inventory build, attributed to growth in channel demand.
INGREZZA prescription trends-- Psychiatry channel represents about 60%-65% of overall volume, with the remainder split between neurology and long-term care; all segments reported similar growth rates.
Summary
Neurocrine Biosciences(NBIX -0.74%) reported net product sales of $682 million, propelled by accelerating INGREZZA and Cranesiti revenues. The company refined its full-year 2025 INGREZZA net product sales guidance to $2.5 billion-$2.55 billion, citing expanded Medicare access and pricing concessions. Cranesiti’s rapid launch generated $53 million in net product sales, with a greater than 75% reimbursement rate for Cranesiti and broad prescriber engagement across pediatric and adult endocrinology settings. Extensive Medicare formulary gains increased INGREZZA's coverage to roughly 70% of eligible Medicare beneficiary lives in the tardive dyskinesia (TD) market as of early Q3 2025. Investments in commercial infrastructure, SG&A, and pipeline programs were emphasized, underpinned by a $1.8 billion cash position as of Q2 2025.
Cranesiti's two-quarter launch momentum was sustained by consistent weekly new patient additions rather than a single bolus event during Q1 and Q2.
Benevich specified the expansion in Medicare formulary coverage was achieved via midyear incremental rebate agreements in Q2 and early Q3 2025, which included all current and future prescriptions under those plans.
Keswani and Roberts presented phase two valbenazine data for adjunctive schizophrenia indicating statistically significant improvements in positive symptoms, as disclosed in May 2025, but not meeting the primary endpoint for PANSS total score in the adjunctive treatment of schizophrenia study for valbenazine, as disclosed in May 2025.
The reimbursement process for Cranesiti did not require most patients to use free goods programs, as over three-quarters of all dispensed prescriptions in Q1 and Q2 were reimbursed product.
Only about 40 adult patients have transitioned from the Cranesiti open-label trial to commercial product so far, with transitions occurring across Q2 and Q3.
Industry glossary
VMAT2 inhibitor: A drug that inhibits vesicular monoamine transporter 2, commonly used in the management of tardive dyskinesia and related movement disorders.
TRx / NRx: TRx refers to total prescriptions written; NRx indicates new prescriptions initiated for a product.
CAH: Classical congenital adrenal hyperplasia, a rare genetic disorder affecting adrenal gland hormone production.
PANSS: Positive and Negative Syndrome Scale, a clinical tool for measuring symptom severity in schizophrenia.
Gross to net: The difference between a drug's gross sales price and the actual net revenue received, after discounts, rebates, and other allowances.
Formulary coverage: Access status of a drug product on a health plan's approved drug list, which impacts reimbursement and patient access.
OLE: Open-label extension, a continuation of a clinical trial where all participants receive the experimental therapy.
Full Conference Call Transcript
Kyle Gano: Thank you, Todd. Good afternoon, everyone. We were especially pleased with our standout second quarter that delivered high double-digit growth, showcased our diversified revenue profile, and highlighted the organization's ongoing evolution. From a commercial perspective, our INGREZZA-based business continues to post solid growth, and we are excited by the strong early performance of Cranesiti. For INGREZZA, our strategic investments to enhance payer access led to a record of new patient starts in TRx for the quarter, further strengthening our leadership in the VMAT2 class. We remain confident that these market access initiatives will continue to drive long-term growth for the INGREZZA franchise. For Cranesiti, we once again outperformed internal expectations.
Today, Cranesiti has been well received by both patients and prescribers, underscoring the significant unmet needs within the classical congenital adrenal hyperplasia community. With a strong product profile across efficacy, safety, and tolerability, we believe Cranesiti is well positioned to become the standard of care for patients with classical CAH and has all the attributes to be Neurocrine's second commercial blockbuster. Coming off a successful ENDO conference this month, I'm reminded of how far we've come. In fact, it was back in March 2015 at ENDO that we first presented proof of concept data in CAH with a CRF receptor antagonist.
Kyle Gano: This year, over a decade later, I had the opportunity to meet directly with clinicians in the field, which gave me an even deeper appreciation for the impact we are making for CAH patients. For the importance of the work we do every day at Neurocrine. Putting patients at the center isn't just a guiding principle. It's what drives meaningful progress. It goes without saying we're deeply grateful to the patients, their caregivers, and families, and investigators who made this progress possible in partnership with the Neurocrine team. We look forward to our continued collaboration. Turning to the clinical pipeline, we believe we have one of the deepest diversified neuroscience-focused pipelines.
I would like to welcome Sanjay Keswani, who officially joined us in June as our Chief Medical Officer. He joins Neurocrine at an exciting time as we have initiated multiple phase three programs within a single calendar year with both OSAV AMPATOR and NVA 568 enrolling patients in registrational studies. At our upcoming R&D Day on December 16, we look forward to sharing additional data from both programs as well as our perspective on the psychiatry portfolio and progress in our R&D transformation.
On the preclinical front, our R&D engine led by Chief Scientific Officer Jude Onye is advancing internally discovered biologics candidates towards the clinic, which further diversifies our mechanistic approach to address a broad range of diseases aligned with our expertise and strategic focus. Overall, I'm pleased with our performance in the first half of the year. Looking ahead, sustained revenue contribution from both INGREZZA and now Cranesiti will enable us to further invest in advancing and expanding our pipeline and, importantly, helping more patients than ever before and solidifying Neurocrine's position as a leading neurology-focused enterprise. With that, I will turn the call over to Matt.
Matt Abernethy: Thank you, Kyle, and good afternoon, everyone. Neurocrine's evolution into a multiproduct growth company was underpinned by $682 million in net product sales during the second quarter, representing 17% year-over-year growth. We expect the profile of both Cranesiti and INGREZZA to drive meaningful revenue growth and generate significant cash flow over the coming years, positioning Neurocrine to become a leading CNS company. Cranesiti grew sequentially from $15 million in Q1 2025 to $53 million in Q2 2025, reflecting strong early adoption by CAH patients and clinicians eager for better treatment options.
Although only six months into launch, we are quite encouraged by what we're seeing in terms of steady new patient starts, greater than 75% of all dispensed prescriptions being reimbursed, and overall positive anecdotal feedback on product performance. As Eric says, so far so great. And kudos to everyone involved in this launch. Shifting to INGREZZA, we delivered $624 million in second-quarter sales, including another record number of new patient starts reflecting the fruits of the Salesforce expansion.
Matt Abernethy: Our DTC campaign, and early positive signs from our investment in expanded access. Importantly, on both NRx and TRx front, we are seeing prescription market share gains in 2025. While we expect to gain volume share for the remainder of 2025, dollar share will be impacted in the near term due to contracting. These are intentional investments that position INGREZZA for continued volume and sales growth as well as market share gains over the coming years. Given current performance and considering market access investments for the remainder of the year, we've refined the INGREZZA net sales guidance range to $2.5 billion to $2.55 billion, which accounts for anticipated double-digit volume gains partially offset by higher near-term growth to net impact.
Overall, INGREZZA is well positioned for continued growth heading into 2026. A few financial comments. Our capital allocation priorities remained intact: drive revenue growth, advance our R&D programs, enable business development, and return capital to shareholders. Our progress in 2025 reflects these priorities with the strong launch of Cranesiti, continued INGREZZA growth, and the initiation of our two phase three programs for osavampitur in MDD and muscarinic schizophrenia trials. We have increased SG&A GAAP and non-GAAP operating expense guidance by $25 million to support continued Cranesiti and INGREZZA sales growth, and we expect SG&A leverage throughout 2025.
With $1.8 billion in cash and a strong balance sheet, we are well positioned to support our commercial and clinical development strategies for continued growth. With that, I'll now hand the call over to Eric Benevich, our Chief Commercial Officer. Eric?
Eric Benevich: Thanks, Matt. Q2 was a quarter of continued strong execution of our INGREZZA growth strategy. Our strategic investments in the INGREZZA franchise over the past year are yielding tangible results. These investments, such as last year's Salesforce expansion, enhanced marketing initiatives, and increased contracting for Medicare coverage, combined with strong efforts from our commercial and medical teams, led to a record number of new patient starts and total prescriptions for the quarter. In fact, this was the second quarter in a row of all-time high new patient starts. Q2 sales of $624 million represented 15% sequential growth and year-over-year sales growth of 8%. In addition, we saw continued prescription VMAT2 market share gains in Q2.
In Q2 and again in early Q3, as Matt noted, we contracted to further expand Medicare formulary coverage for INGREZZA. We now have formulary coverage for approximately 70% of Medicare beneficiary lives in the TD market. These incremental rebate agreements were mid-year adds to key formularies outside of the regular bid cycle. They substantially improve our coverage and will make it easier for patients and providers to start or reinitiate INGREZZA therapy going forward. The formulary adds in Q2 and Q3 represent approximately a 25% increase in coverage in just two quarters and embody the stellar work done by our market access team.
We acknowledge that these rebate agreements encompass prescriptions for all current and reservations insured under those plans, not just the new incremental patients. So we saw an impact on our gross to net, which somewhat offset our strong volume growth. However, we believe that over time, these Medicare formulary investments will allow us to grow our volume and share faster than we otherwise would. With less than half of the estimated 800,000 TD patients yet diagnosed and approximately thirteen more years of exclusivity, we believe these sales, marketing, and access investments position the INGREZZA franchise well for growth in the years to come. Now turning to Cranesiti.
The launch is off to a strong start with early results surpassing our internal expectations. In Q2, we received 664 new treatment forms and over a thousand have come in since we launched in late December. This was an important milestone for our franchise. Q2 net sales were $53 million, more than triple our Q1 sales, and over 75% of all dispensed prescriptions in the quarter were reimbursed. Clearly, we're building strong momentum with this launch. To date, we've seen widespread adoption across both pediatric and adult patients with a slight trend towards pediatrics after two full quarters on the market.
Furthermore, we have seen prescriptions written by a range of CAH healthcare providers, including those practicing at multidisciplinary centers of excellence, pediatric endocrinologists, and community-based adult endocrinologists. Given the early stage of the launch, most individual prescribers have only initiated treatment for one or two patients so far, which is to be expected.
Eric Benevich: Now let me share a little color on the launch. Earlier in July, our commercial and medical teams had a strong showing at the Endocrine Society Annual Meeting in San Francisco, where we presented 16 posters, including long-term Cranesiti efficacy and tolerability data, and weight-related outcomes. Attendance at our commercial and medical booths as well as our sponsored symposia was very good. Feedback from endocrinologists who have already treated patients with Cranesiti was quite positive, and the interest level was high amongst those who haven't yet had a chance to prescribe. With two full quarters complete, Cranesiti's performance continues to trend very positively.
We have all the right ingredients here for a future blockbuster: high unmet need, strong efficacy and safety data, a broad and favorable label, and highly dedicated teams who put CAH patients' needs first. Once again, I'd like to thank our commercial and medical teams for driving strong results for both INGREZZA and Cranesiti in Q2. And with that, for the first time ever, I'll hand the call over to my new colleague, Dr. Sanjay Keswani, our Chief Medical Officer.
Sanjay Keswani: Thanks, Eric, and good afternoon, everyone. Before I begin, I want to express how enthusiastic I am to join Kyle and the Neurocrine team as Chief Medical Officer. I'd also like to acknowledge my predecessor, Dr. Eiry Roberts, for her remarkable leadership and the significant clinical advancements accomplished during her tenure. I'm grateful that Eiry will continue to support us as a strategic adviser through the end of next year. Now onto the clinical update. The registrational studies for both osavampitor in major depressive disorder and NBI-568 in schizophrenia are progressing well. Indeed, we have just screened the first patient in our second phase three study in schizophrenia for 568.
Hence, all the phase three studies as well as the open-label studies for 568 and osavampitor are up and running. We anticipate top-line data readouts for osavampitor in 2027 and a bit later for 568 in the 2027-2028 time frame. Regarding data readouts this year, we disclosed in May that for the adjunctive treatment of schizophrenia, valbenazine did not meet the primary endpoint of improvement in the positive and negative syndrome scale or PANSS. Recall, this study was designed as a learning opportunity for our next-generation VMAT follow-on programs and has indeed provided valuable insights. Notably, we observed numerical separation and improvements in the valbenazine arm compared to placebo, as well as statistically significant improvement in positive symptoms.
We look forward to sharing the full study results at an upcoming scientific meeting. Continuing with valbenazine, top-line results from our phase three study for the treatment of dyskinetic cerebral palsy will read out in Q4 of this year. In addition, the phase two proof of concept and dose-finding study for NBI-770, our NMDA NR2B negative allosteric modulator, will also read out top-line data in Q4. With a positive readout, these data could pave the way for a confirmatory phase two study or the initiation of a phase three trial.
Turning to our new programs, last month we announced the initiation of the phase one study for NBI-1435, a long-acting corticotropin-releasing factor one receptor antagonist administered subcutaneously for the potential treatment of congenital adrenal hyperplasia. This program marks the first investigational PET from our internal pipeline to advance into the clinic. It's also the first of what we anticipate to be many biological compounds advancing from Chief Scientific Officer Jude Onye's research division. Regarding our early-stage muscarinic programs, we remain on track to initiate the phase two study of NBI-570, our dual M1M4 selective agonist for the treatment of schizophrenia.
We also expect to report phase one results later this year for both NBI-567, our M1 preferring dual agonist, and NBI-569, our M4 preferring dual agonist. I look forward to engaging with many of you over the coming months ahead in advance of our R&D Day at Neurocrine's campus in San Diego on December 16. With that, I'll hand the call back to Kyle.
Kyle Gano: Thanks, Sanjay. I think we're ready for questions now.
Operator: Thank you. At this time, if you would like to ask a question, please press star one on your telephone keypad. Once again, that is star one to ask a question. And our first question comes from Tazeen Ahmad with Bank of America.
Tazeen Ahmad: Hi, guys. Good afternoon. Thanks for taking my questions. Mine, I think, is going to be for Matt. Matt, we know that you're super detail-oriented. But taking that into account, you're narrowing the top end of guidance by $50 million, and we've still got half of the year left. And I fully appreciate the comments that you made about having midyear ads and improving access on Medicare. But I guess how are you triangulating that level of certainty? And is that number potentially up for future adjustment as the year progresses? Thanks.
Matt Abernethy: Yeah. Thanks, Tazeen. It really comes down to the contracting and where net price was coming into the year. As you mentioned, I am detail-oriented. And so I never like to have anything changed throughout the year, but that's not the case of our business. Very dynamic. And on the pricing front, we had assumed a flat pricing coming into the year based upon the contracting in place. But throughout this year, we've been able to pull forward actually some major programs from in contracting from 2026 into 2025. So from a pricing perspective, it went from flattish pricing expectations to call it, negative 5% price decline for the year.
And so I think that should help triangulate where the guidance range is at. From a volume perspective, kudos to the team. Record numbers of TRx, record numbers of new patients, double-digit volume growth. So on the volume side, everything is going well for us as well as in the marketplace. This adjustment down on the top end really comes back to a change in assumption around price.
Operator: We'll move to our next question from Phil Nadeau with TD Cowen.
Phil Nadeau: Good morning. Good afternoon. Thanks for taking our question. Congrats on the Cranesiti number. It does seem to be launching much more quickly than most of us had anticipated. Can you talk about the dynamics you're encountering at the clinics? In particular, were there any boluses of patients headed to Cranesiti during the quarter? Any reason why we shouldn't extrapolate the growth we saw in Q2 to future quarters or any other dynamics that we should consider as we try to digest the big number you just put up and what that portends for future quarters? Thanks.
Kyle Gano: Yeah. Hi, Phil. So I'll comment, and maybe Eiry has some additional commentary here. But before the launch and after Q1, we had sort of guided towards what we call the measured launch. And the reasons for that were primarily around patient flow through the practices. We know that adult patients usually only see their endocrinologists once, maybe twice a year, pediatric patients two or three times a year. And endocrinologists had indicated to us that they intended to offer Cranesiti treatment as patients flow through. Those dynamics haven't really changed. We're still seeing that patients are being initiated subsequent to an in-person visit. That being said, we have seen strong adoption.
Obviously, we feel really good about the pace of patient starts. And it's building over time. Certainly, I think it's a function of our ability to reach the endocrinologists and to get the word out within the patient and family communities. So, kind of getting back to this concept of a bolus, no. It's not really a bolus or patients that were necessarily waiting for Cranesiti because for the most part, people weren't aware of it prior to its approval. But we have seen what I would describe as very steady and consistent adoption.
And certainly, we view the activity that we had at Endo as sort of another booster for us in terms of being able to accelerate that awareness within the endocrinology community.
Eiry Roberts: Hi, Phil. Thanks. The only thing I'd add there is I mean, I do think we have a lot of interest and excitement out there in the community. They were receiving a lot of questions from patients and requests from patients to get in and get the opportunity to talk about Cranesiti. Certainly, the other place you'd think of a bolus is if there was one coming from the clinical trial environment. And as you know, we signaled that we were shutting down the adult open-label trial, and those patients are steadily moving onto commercial Cranesiti, so it isn't a bolus effect there either.
And, obviously, we still have our pediatric open-label extension trial going, which is going to provide us with longer-term clinical data that we think will be very important.
Operator: We will move next to Paul Matteis with Stifel.
Paul Matteis: Hey, congrats on the great progress with Cranesiti. Thanks for taking my question. I was wondering if you can share any data or metrics or at least qualitative color on how concentrated prescribing has been at this point? You know, if we look at some other rare disease launches that have had a great start, but maybe tapered off after a bit, it feels like there can be this sort of COE academic dynamic and then the patient acquisition effort increases over time as you have to go to the community. So how do you think CAH stacks up with these sort of treatment dynamics and what you're seeing with Cranesiti? Thank you.
Eric Benevich: Yeah, Paul. So, you know, certainly, we're very excited about the adoption that we're seeing. And, you know, prior to the launch and subsequently, you know, our estimate has been that, you know, if you think about sort of three segments of endocrinology prescribers, you know, we've got our centers of excellence that are accredited, and then there are others that are not accredited by the Cares Foundation. Overall, you know, we estimate that around 15% or so of the total CAH patient population flows through a small number of those centers. Let's call it, 20 or less. And then, you know, an important segment is also the pediatric endocrinologist. There's a little over a thousand of them out there.
They care, you know, for all these pediatric patients and even some of the young adults. And then, there's the community endocrinologists. And that's where, you know, as we say, the tail gets long. Ultimately, though, this isn't a super concentrated patient population. You know, somewhere north of 20,000, we estimate, in the US. And most of the adult community endocrinologists, if they have CAH in their practice, they have one or two patients. And so in my prepared remarks, I commented that most of the prescribers so far have written for one or two patients. And in some instances, that's all they have. But, certainly, we see a lot of HCPs that have yet to prescribe.
And in those centers of excellence, there's still a lot of room for growth in terms of adoption. So it's still early days yet. We're two quarters in. We're pleased with the trajectory of the launch. But, you know, for the most part, this isn't a super concentrated patient population.
Eiry Roberts: Hi, Paul. The only thing I'd add there is that I think we are hearing that given the breadth of the label and the efficacy and tolerability data that was generated for Cranesiti, the ease of starting the therapy is helping ensure that it isn't something that is requiring that center of excellence presence in order to be able to get patients onto the medication.
Matt Abernethy: Sorry. This is an exciting one. So the last add here from the team. When you look at how steady the new patient additions were throughout the quarter, I mean, it was very consistent within a pretty tight range week by week. So I think if we would have had some inflection or some bolus effect, I don't think you'd see the steadiness in terms of overall adoption. And new scripts written each week. So kudos to the team for finding these patients and getting them help, and then also for the reimbursement team to be able to have above 75% of scripts reimbursed at this point. Just quite an accomplishment.
Operator: We'll go next to Cory Kasimov with Evercore.
Cory Kasimov: Hey, good afternoon, guys. Thanks for taking the question. Wanted to follow-up on Eiry's earlier comment on the adult OLE program in patients rolling from that over to commercial product. Are you able to provide any more granularity there in terms of percentage of patients that have moved over and whether you would expect the rest to follow suit? Are there any nuances in this process that would perhaps prevent them from doing so? Thank you.
Eiry Roberts: Hi, Cory. So we're talking about less than forty patients here. And you're going to see some of those. We saw some fall into Q2 and some fall into Q3. In the context of over six hundred patient starts in the quarter, you know, pretty de minimis in terms of the overall landscape of what we're seeing with Cranesiti.
Operator: We'll go next to Jay Olson with Oppenheimer.
Jay Olson: Oh, hey. Congrats on the Cranesiti launch success, and thank you for providing this update. I wanted to thank Eiry for her substantial contributions and wish her all the best. And I also wanted to welcome Sanjay. So congratulations on joining the team. And could you please share with us some of the key findings that you learned from your due diligence that attracted you to Neurocrine? Thank you.
Sanjay Keswani: Nice to meet you, Jay. Yeah. I'm super excited to join Kyle and the Neurocrine team, and yeah, I'd also like to acknowledge Eiry, who's sitting just beside me, for her terrific leadership. Yeah. In terms of some of the reasons I joined, I thought the company was really at a transformational stage, evolving from primarily a small molecule to product company to potentially a multiple modality company targeting multiple therapeutic areas with multiple products. So the potential here to positively impact the lives of many patients and their families who are suffering with unmet need is a major source of motivation for me.
With respect to the portfolio, my perspective is that the late-phase psychiatry portfolio has a high probability of success because they're essentially validated targets. And I'm also really excited by our large early-phase portfolio, which largely comprises large molecules such as bispecifics, antibody-drug conjugates, and peptides, with many of these programs having transformational potential. And as Kyle mentioned, we will discuss some of this at our R&D day later this year. So I think that Neurocrine has walked the talk with respect to substantial R&D investment. So thank you for the question.
Operator: We'll go next to Brian Abrahams with RBC Capital Markets.
Brian Abrahams: Hey, good afternoon. Thanks for taking my question. I'm curious if you could talk about what steered your decision to contract INGREZZA midyear. How long these contracts, we should think about these contracts generally being in place for? And should we not expect now additional contracting shortly after the new IRA price is established for your competitor? Thanks.
Kyle Gano: Hi, Brian. This is Kyle. You probably heard from me when I stepped into the role. A lot more conversation about looking at maximizing access for patients. I think it's something that is important to me and the company. And it's always been a north star for us to do that for patients. We think that's in their best interest. In terms of offering options for their care. Also think it provides a great deal of flexibility for us moving into the new era of IRA that starts next year with the first round of 10 that go through their price negotiation.
So as you know, with the contract process, this starts well in advance of the year that you're looking to actually observe your new price, if you will, and our contracting efforts that we outlined here were actually started initiated with the mindset that we begin in 2026. And, obviously, when you start the year in these discussions, you don't know where they're gonna go. But we got them to a good place for '26 and the opportunity to accelerate or pull them forward into 2025. So you saw some of the efforts there result into an advantage for us starting in Q2. And then another one that has played out for the start here in Q3.
So that's where we are today on this. I think that's part and parcel of where we landed on narrowing the band of our guidance to $2.5 billion to $2.55 billion. But I do want to go back to a point that Matt started earlier in the call. What we saw here in Q2 was a second quarter of new record, new prescriptions as well as total prescriptions. And that led to a market share increase in Unibrand prescriptions as well as total prescriptions. That doesn't happen by chance eight years into commercialization. It really is a function of sound business fundamentals. And this is across our Salesforce expansion that started later or late last year.
Through the marketing initiatives that we outlined for this year and the market access advantages that we now have. So you pair those together with very strong demand in the patient segment within TD, and we're seeing the uptick in the volume that we think is very important for our business. This year in terms of new patient starts. Even more important in 2026. We're gonna start off on day one on a good foot, and really have a strong year. So I think that gives you a nice feel for our contracting process and thoughts here for this year in '26.
Matt Abernethy: Yeah. I think, Brian, you were also wanting some clarification around any additional contracting that we would expect to take place and just do want to build on what Kyle said. In that, you know, we believe this sets us up really well for 2026. So sitting here right now, I do not expect or believe there's gonna be any major contracts signed that would segregate pricing further from how we're exiting 2025. So sitting here right now, we would expect very similar pricing into 2026 based upon the amount of coverage that we have. But we'll, of course, update everybody if that were to change.
Operator: We'll go next to Anupam Rama with JPMorgan.
Anupam Rama: Hey, guys. Thanks so much for taking the question, and congrats on the Cranesiti launch. Quickly on the valbenazine, gets update, what are you learning from that study on VMAT2 mechanism in schizophrenia, target population considerations, or trial design considerations as you look to the next-gen VMAT two? Thanks so much.
Sanjay Keswani: Yeah. I think it's as you've mentioned, important to understand that study in ATS was a learning opportunity for us, specifically for our VMAT2 follow-on programs. So what we saw was essentially some positive efficacy signal in the positive scale within the PANSS score. And so I think that will be very helpful in terms of understanding the target patient population for the other programs that are following valbenazine. But I don't know, Eiry, if you want to mention some more things.
Eiry Roberts: Yeah. No. Happy to. Nice to talk to you, Anupam. I think the first thing to say was it was a well-designed, a well-controlled, large study. So, actually, I think we were very pleased with the level of the data and information we're able to get out of the study, so that was a good thing. Secondly, I think it's really helpful that it confirmed in a larger population of 400 patients the safety and tolerability profile that we knew was there for valbenazine, but it's good to see it in these more acutely unwell individuals.
We obviously, beyond the PANSS positive score and the PANSS total score, were able to look at a whole series of, you know, the subscores and additional quality of life functional measures and other things of that sort. And what I'll say is that there were some interesting signals in there across the subscores, that we will intend to publish on in due course over the next few months, and we'll obviously use that knowledge as well to inform the next generation of VMAT two inhibitors in terms of choice of patient population, indications, and other elements.
Operator: Pulling in next to Brian Skorney with Baird.
Brian Skorney: Hey, good afternoon, everyone, and thank you for taking the question. Also on Cranesiti, congrats on a really strong quarter. So maybe you could maybe give us a little more detail on the derivation of that bigger. Is there any inventory dynamic in this quarter? And can you disclose the number billed prescriptions represented here? It just seemed hard to calculate more than, like, 2,000 TRx in the quarter given the patient's start forms and reimbursement numbers you gave us. Which puts the net TRx somewhere in the high 20,000 range. I guess, are we in the right ballpark with those numbers?
And how do you think about pricing going forward both on sort of gross to net and mix of adult and pediatrics? Thanks.
Matt Abernethy: Yeah, Brian. On the inventory front, because I've seen some notes on this, but on the inventory front, what we had in the quarter was a build of around $5 million, so that's just reflective of growth in the channel as the scripts continue to grow. You know, as we've said before, very consistent demand throughout the quarter, very good job from our pharmacy getting patients ultimately on therapy. And gross to net so far has largely been on the heels of co-pay assistance as well as some distribution fees and costs. And like we've said, I haven't been at a place of contracting yet. So good job to the team so far.
Operator: We'll go next to Yatin Suneja with Guggenheim Partners.
Yatin Suneja: Hey, guys. Thank you for taking my question. I have a question regarding the IRA implication. If you can just maybe talk about how do you envision the access to shake out? I mean, what would be the end goal? Will you seek access at parity once we know the negotiated price? Just curious if you can outline that dynamic for us the best you can and also your expectations on how, you know, whether one drug will be mandated versus the other. Thank you so much.
Kyle Gano: Yes. This is Kyle. I'll start a response here. I'll ask Eric to fill in any holes in my answer here. I think for IRA, I mean, there's a couple pieces here that I would point you to. There's our own IRA moment in 2029. That's when our negotiated price is enacted. And then there's our competitor in this space. So due to rate of tetrabenazine in 2027. And if you wanted to speak to the near term, event, with our competitor, I think we start with we acknowledge we don't have all the answers, what's gonna happen during an IRA. I don't think anyone does. So I think we all acknowledge that piece.
It's a good place to land on. In 2025, we're gonna see what happens with other brands in the same categories for medicines are negotiated. So I think we'll have some learnings there. And then the therapies I'd point out is, you know, our goal here is to maximize the number of patients on INGREZZA. That's part of our maximizing our access strategy here. And I think that's important to point out because INGREZZA is incredibly sticky. Patients, when they start INGREZZA, they tend to stay on it. When it comes to 2027 in the years between that and our own IP moment in 2029, we are talking about the new patients, primarily.
And we think that we're on a good footing here with the differentiation that we offer for INGREZZA relative to our competitor in this space, they go through their iPay moments. Maybe I'll stop there. Eric, anything to add?
Eric Benevich: Yeah. Just want to reinforce that I think we're all gonna learn together in 2026 in terms of how health plans are managing various classes, whether it's one or more negotiated products. And, certainly, our overall strategy from an access perspective is to have broad access and parity. And, over time, we've been very successful with that. Obviously, you know, we commented that in 2024, we started to see some tightening of access in terms of health plans starting to reject more claims and so on. This wasn't specific to INGREZZA. This was more of a broader industry trend, and that's, you know, carried forward into 2025.
Frankly, that's one of the reasons that we've invested in access because, you know, we believe it's very important to make it as easy as possible for providers and patients to get on product. And, certainly, these increased investments that have led to a higher proportion of covered lives in Medicare sets us up well for 2026 and beyond. So you know, we're going to very carefully monitor the environment but ultimately, the goals don't change. We want to help patients. We want to make it available. And how we go about doing that is probably going to evolve over time.
Operator: Hi, Jess. Are you there? I you've heard me break.
Ami Fadia: There you go. Hi, Ami.
Operator: Hi. What's your line? I con okay, great. Thanks for taking my question. Okay, question on Cranesiti.
Ami Fadia: Can you give us a sense of the penetration across the different segments of the market from a physician perspective? That you've talked about and you mentioned that at present, mostly physicians have one or two patients on treatment. That is likely to evolve over time. How long do you anticipate physicians, you know, sort of limit to maybe, you know, a handful of patients before they feel like they have enough experience with the treatment to start to expand that? Thank you.
Eric Benevich: Yeah. So I'll kinda go back to some of my prepared remarks. You know, we recently crossed an important threshold of having over a thousand NRxs submitted treatment forms submitted into our patient hub. And most endocrinologists have only that have treated, have only treated one or two patients so far. And the reality is, as I mentioned earlier, this is sort of a thinly spread population. Most of the adult endocrinologists, if they have any classic CAH patients in their practice, they might have one or two. So in some instances, they've treated all the patients that they have. However, you know, especially within pediatric endocrinology and in those centers of excellence, there's still a lot of untreated patients.
And so we have a long way to go. Frankly, in terms of adoption. It's still two quarters into a launch. And there's certainly endocrinologists that we have yet to meet with and to walk through the clinical data and the labeling. So I would say, you know, if you want to try and calculate how many prescribers there are, certainly looking at the number of treatment forms coming in and sort of that ratio where most have only one or two, you can get a sense that it's less than that total number.
But, ultimately, you know, I think that we'll see how things evolve as we move further into the launch and we continue to raise the awareness of not only the availability but of the benefits of Cranesiti.
Operator: We'll go next to Corinne Johnson with Goldman Sachs.
Corinne Johnson: Good afternoon, everyone. I wanted to ask on the reimbursement process from here. When you anticipate transitioning to more of a formulary-driven process, then how do you anticipate that could impact net pricing on Cranesiti?
Eric Benevich: Yeah. Let me tackle that. So at launch, Cranesiti was a non-formulary drug everywhere. And our expectation is that in some instances, health plans will decide to do a formulary review and, you know, often they'll add it to formulary. But given that it's a class of one, it's more likely that in many instances, they won't bother to do a formulary review, and it will remain as a non-formulary product. That doesn't mean that it's not covered. And, certainly, we're very pleased with the rate of reimbursement that we're seeing.
Our expectation coming out of the gate with the approval was that in most instances, patients would need to go on to our free goods program for a month or possibly longer before getting their prescription claim approved and then transitioning over to commercially reimbursed. The reality is that we've been pleasantly surprised at the fast rate of approvals for these claims. Most patients don't need to go on free goods. And that's the statistic that over three-quarters of all the expenses, both in Q1 and in Q2, have been reimbursed product.
So just to set expectations, I don't know that we're ever going to be in a place where, you know, we'll provide formulary coverage statistics because in many instances, health plans will continue to reimburse as a non-formulary product given the size and scope of this category.
Operator: We'll go next to Danielle Brill with Truist.
Danielle Brill: Hi, guys. Good afternoon. Thanks for the question. You mentioned some of the data that you presented at Endo. And I was just curious about some of the feedback that you received there from the prescribing community specifically as it relates to, like, the change in dose at one year remaining relatively flat versus twenty-four weeks, and how we should think about that. And then same thing on the insulin resistance data that you presented. It seems like we don't see further benefits beyond twelve months. Is there anything to read into there? Why might that be?
And then at any point in time, will we see any additional clinical data such as bone age data or other benefits from lowering steroid doses? Thank you.
Eiry Roberts: Hi. It's Eiry here. I'll address the last bit first. Yes. We do have ongoing open-label trials for Cranesiti both in adults and pediatrics, the adult patients being outside the United States, pediatrics being worldwide. And our intent is to continue to publish over the long haul from those studies because we do believe that those longer-term clinical data are absolutely critical. Just as a reminder, this was the first time that we had presented one-year data from our registrational program. And the first time we'd really been able to concentrate on those clinical outcomes that are so important to patients and to clinicians.
And just again by means of kind of reminding everyone, you know, the impact of Cranesiti is to have a direct impact in lowering androgens, and so we're interested in understanding the long-term impact of controlling those androgens over a twelve-month period and even beyond. And then secondly, as a result of that reduction in 17 OHP, ACTH, and androgen levels, that we're able to achieve directly with Cranesiti, we are able to reduce the steroid dosing in these patients from the superphysiologic doses that are required to control the disease in the absence of Cranesiti.
Going into the release of data from this program, we had said, and this was supported broadly, that any reduction in steroid dose was beneficial to patients over a lifetime, and I think that is in fact what is playing out. What we saw in the one-year data was a consistent small, modest effect, but a consistent effect across many metabolic parameters including weight, Homer IR, the insulin that you referred to, and you know that is a clinically beneficial change that we saw there that results in a potential for improved outcomes over a lifetime for those patients. It's extremely important.
We also saw changes in scores such as hirsutism scores in females which are important in terms of looking at the direct androgen effect. So in with the release of all those data, I will say that the response from the community was actually very positive. Clinicians were very interested and excited in the data, looking forward to obviously continuing to follow those data over time. But it's a really good start from our point of view in terms of how we're able to serve patients.
Operator: We'll go next to Mohit Bansal with Wells Fargo. Your line is open. Please go ahead or check your mute button.
Kyle Gano: I guess we'll catch Mohit on the flip side. Can we go to the next one, Jess?
Operator: We will go next to Ash Verma with UBS.
Ash Verma: Hi. Thanks for taking my question. Just a quick one on Cranesiti formulary commentary that you made. So out of all of these reimbursement for a 6,000,000 to six-month or one-year basis, then when Cranesiti is up for reauthorization, for these patients, would that require steroid dose reduction? Based on what you can tell right now? Thanks.
Eric Benevich: Yeah. So if I understand your question correctly, it's related to reauthorization, you know, what are we seeing in terms of the authorized number of fills and timing for the authorization? And what kind of criteria are required. For the most part, you know, what we're seeing is patients either getting six prescriptions, fills authorized initially or twelve. That seems to be the pattern generally. And, for the most part, plans have that if they have published their approval criteria, they haven't necessarily published reauthorization criteria, but typically, what we're seeing now is sort of that first early cohort of patients that might have gotten on to commercial product early in the launch that are getting reauthorized.
Generally, it's the provider affirming that they're benefiting from treatment. So we're not seeing any hard and fast thresholds of GC dose or GC dose change or, you know, needing to provide labs related to the ACTH or the androgens. So for the most part, the reauthorization process has been going about as smoothly as the initial authorization process.
Operator: We'll go next to David Amsellem with Piper Sandler.
David Amsellem: Thanks. So I had a question on the pipeline, particularly the M1, M4 agonist 570. So I'm sure you're watching Bristol's work with Kobemti with significant interest. And what I wanted to ask is to the extent that the ADAPT two study in Alzheimer's psychosis reads out favorably later this year, how does that play into your development plans potentially to get more aggressive with the advancement of 570, say, in AD psychosis or potentially other indications? I know you have the schizophrenia study enrolling, but how are you thinking about that more expansively? Just given its mechanism and that it's precedented by another M1, M4 on the market. Thank you.
Sanjay Keswani: Great. Yeah. So we are watching Kobemti's data with interest. Of note, we have quite a robust muscarinic portfolio. So we have a number of M1 preferring, as well as M4 preferring agonists and as you mentioned, a dual M1 M4 570. So we have a number of choices in terms of which ones we take to various indications. Indeed, AD psychosis is a really important indication for the field. And we are interested in that. It may be with 570, but we have other muscarinic agonists which actually may be better suited for that rather elderly population because potentially, there's a superior safety profile associated with it. Are there any more questions? Any more? No.
I think that was well said. And just to pick up on what Sanjay said, at the end, I think one of the things that, obviously, we're watching the Kobemti data very closely, but, you know, we do believe that the direct agonist approach here without the need for an add-back, particularly in that older population, could provide an opportunity for differentiation if we were to go forward.
Operator: We'll go next to Marc Goodman with Leerink Partners.
Marc Goodman: Yeah. Matt, just to confirm, this negative 5% INGREZZA ASP comment for the year, is this a full-year impact? I'm kind of assuming that the second half is lower than the first half for ASP. So you say there's no change for ASP in 2026, are you referring to the full-year ASP? Are you referring to where you actually are kind of ending the year, which is lower than kind of the average for the year if you understand my question. Thanks.
Matt Abernethy: Yeah. Regarding the 2026, it's a trajectory comment, how we're exiting the year in 2025 would be what you would expect to continue into 2026. So appreciate that clarification. In addition to that, on the net price comment, for the year for 2025, the negative 5% price, as you mentioned, it's more concentrated in the second half of the year. So that was a full-year commentary. So it is safe to assume that the price headwind is a bit more in the second half as compared to the first half. But with that said, I think you take a step back and you look at the volume gains that we expect to have, and it's just an incredible market.
And feel like we're really well positioned with these formularies to continue to grow and build the market.
Operator: We'll go next to Myles Minter with William Blair.
Myles Minter: Hi. Thanks for checking the question. Can you just remind us of the discontinuation rates for Cranesiti and the one-year open-label extensions to the pediatric and the adult studies? Is that still probably the best proxy we have for the annualized retention rate on the real world or other key factors we have to consider for retention basis? Thanks very much.
Eiry Roberts: Yeah. Hi, Myles. I think the first thing to say is that we were very favorably surprised, I guess, at how well tolerated and how safe Cranesiti was across the adult and pediatric population. That's the first thing to say. We had just a very small number of patients discontinued during the course of the program, and more than ninety-five percent of the patients roll over from both the pediatric and the adult program into the open-label extension. Many of those patients have now been on study for greater than three years, and we still continue to see very low discontinuation rates. And a continued improvement in the outcome for those patients.
Matt Abernethy: So it's still early in the launch cycle for Cranesiti, and we're watching that, of course, over these first six months. But that's a key variable as we think about what's the long-term potential of Cranesiti. And that's something I think we're gonna know a lot more here in the second half of this year as well as then into the first half of next year as you see patients getting blood draws and understanding glucocorticoid titration. But from a safety and tolerability perspective, as Eiry said, three years of patients on therapy, we have a lot to believe in terms of high levels of adherence.
Eric Benevich: Yeah. One last point to make, you know, in terms of the difference between real-world and clinical trial experiences. You know, typically, in the real world with the medicine, affordability and coverage can impact persistency. We're seeing really, really good coverage, and we believe that Cranesiti is very affordable for patients, you know, between the co-pay buy-down and the other programs that we have. So we don't expect insurance to be a barrier to persistency.
Operator: We'll go next to David Hoang with Deutsche Bank.
David Hoang: Hi there. So first, I just wanted to ask in terms of INGREZZA, so a competitor, Zotava, reported this morning. I believe they raised their guidance for their product, Steadow, for the year. Is there anything to maybe read into that as pertains to the relative growth of INGREZZA versus your competitor this past quarter and market share in terms of dollars? And then just quickly on CAH, I think you talked about 20k prevalent patients in the US. Do we have a sense of what percentage is regularly followed in clinics maybe from things like medical claims data? Thanks a lot.
Kyle Gano: Yeah. This is Kyle. I'll take your first question. It comes to our competitor in this space, you know, we don't really speak to the dynamics of their marketplace and what they're looking at. I think from the perspective of INGREZZA, I'm extremely encouraged by the volume growth that we saw this quarter. But I do want to reiterate we increased our market share on both new to brand as well as total prescriptions. And so I think that we're really happy with the performance in the first half of this year.
You combine that with our initiatives that we put in place starting the year with our additional market access, and we are looking forward to a strong second half as well. So I think I'll leave that there for the time being. And then on the Cranesiti side of things, Eric, you want to comment on that?
Eric Benevich: Yeah. I just want to reiterate that our estimate is greater than twenty thousand patients in the US. And the reason that it's an estimate and not a firm number is that some of these patients, there first of all, there is no specific ICD 10 diagnosis code for classic CAH. There is a CAH diagnosis code that encompasses both classic and nonclassic patients, and look at the medical literature, for every classic CAH patient, there's three or possibly four nonclassic patients. So, you know, we have had to triangulate, you know, doing a thorough medical literature review, looking at claims data, and so on to get at that number.
Some of these patients don't have the 20,000 number in the US is a good estimate for the overall prevalent populations, a subset of them that are more easily findable. Guess, is the way I would put it. And, certainly, there are, you know, that are under the care of an endocrinologist, for example. But there are certainly a cohort of classic CAH patients that are not under the care of an endocrinologist, and they're probably being seen by internal medicine, family medicine, or even OB GYN. So it you know, we will learn more about this market as we get deeper into the launch.
Operator: We'll go next to Sumant Kulkarni with Canaccord.
Sumant Kulkarni: Good afternoon. Thanks for taking my question, which is science-based but could have significant strategic and stock implications. You have several years of internal experience in CRF1 receptor antagonist. Corticotropin is involved in stress response, and there's some intriguing external preclinical data on binge eating, this approach. Now that you presented one-year data on weight-related effects of Cranesiti at Endo, are your thoughts on using this approach specifically for weight loss, especially as you have a longer-acting version in the works which could help in compliance in that setting?
Eiry Roberts: Yeah. We're clearly very encouraged by the data that we saw from the one-year readout recently at Endo for Cranesiti. And as you can probably imagine, we have a wealth of knowledge about CRF1 antagonism and CRF biology here at Neurocrine. So as we go forward, we'll be considering a broad range of potential indications and also, obviously, we have a breadth of other research projects in our pipeline that may well seek to address some of those challenging disease areas moving forward.
Operator: We'll go next to Sean Lehman with Morgan Stanley.
Michael Riad: Hi. This is Michael Riad on for Sean Lehman. Thank you for taking our question. For INGREZZA, could you comment on the current volume split between the neurology, psychiatry, and long-term care channel? And regarding the double-digit volume growth you expect this year, could you provide any more color on respective contributions to that volume growth from the respective channels? Thank you.
Eric Benevich: Yes. I mean, what we saw was strong growth really across all three of the business segments. Overall, psychiatry accounts for about 60 or so percent of our volume and, 65% maybe. And then the balance is split, you know, between the other two segments pretty evenly. But all of them are growing at approximately the same rate, so we're really pleased with the overall growth trajectory for the franchise.
Operator: We'll go next to Laura Chico with Wedbush Securities.
Laura Chico: Thanks very much for taking the question. On Cranesiti, I wanted to dive into a little bit more about the cadence of prescribing and kind of just clarifying one, have the majority of patients transitioned from studies to paid script status at this point? Two, as we're thinking about increasing breadth of prescribing, I guess, is there kind of an upper limit as to how many patients physicians are gonna be able to manage on Cranesiti? I guess, is there any capacity constraints that you can share? Thank you.
Eric Benevich: Yeah. We don't see any capacity constraints in terms of managing patients on Cranesiti. It fits right in the they're already being cared for, and we have a really good pharmacy partner to help with that. And so I'll leave it there.
Matt Abernethy: And we'll check our final Sorry. Laura, I forgot to mention. In regards to clinical trial patients, as I said earlier on the call, it's less than 40 patients, and you could assume half of them came on board in Q2 and the other half are going to come on board in Q3. So it's pretty de minimis in terms of overall new patients that are being added to therapy.
Operator: And we'll move to our final question from Evan Seigerman with BMO Capital Markets.
Evan Seigerman: Hi, Thank you so much for taking my question. Wanted to touch on some of the thinking behind moving 568, excuse me, into phase three. So I know the phase two trial is in CA dose response. Can you walk me through what you were able to look you get in the data to give you confidence in moving to this larger phase three program. Thank you so much.
Kyle Gano: Well, I think we've discussed the merits of moving 568 into phase three. I will mention here we do have an INN name, so I wanted to do a shout out to the team for putting that together for us for this meeting. It's dereclidine. So stay tuned on that. We'll be able to put that in future correspondence and releases out there. Think, again, I'll refer back to our phase two commentary around the totality of the data that we have. All doses worked in our phase two and for the dose that we selected for phase three. We hit the primary endpoint with all the secondary endpoints as well.
Very attractive profile overall from an efficacy, safety, and tolerability profile. We think that will differentiate quite nicely if we're able to reproduce those results in phase three relative to cobenefi out there today.
Operator: And that will conclude the Q&A session for today. I'll turn the program back to Kyle Gano for any additional or closing remarks.
Kyle Gano: Thanks, Jess. Thank you all for your thoughtful questions and engaging discussion this afternoon. We covered a lot of ground in particular, across our commercial portfolio and our pipeline. And I hope you're seeing a transition of the company to one defined by both revenue growth and diversity, I should say revenue diversity, moving forward with both INGREZZA and Cranesiti. Forward to connecting at upcoming healthcare conferences and certainly in our R&D Day on December 16. So thanks again for joining. Talk to you soon.
Operator: Thank you. Ladies and gentlemen, that will conclude today's call. We thank you for your participation. You may disconnect at this time.