Axsome Therapeutics Inc

NASDAQ:AXSM

Earnings Call Analysis

Axsome Therapeutics Reports Strong Q3 Performance and Strategic Growth Plans

Axsome Therapeutics achieved a pivotal milestone with Q3 total net product revenue reaching $104.8 million, marking an 81% increase year-over-year. Auvelity's sales surged to $80.4 million, growing 113% compared to last year. Sunosi also showed strong performance with a 21% revenue increase to $24.4 million. The company plans to expand its sales force by 300 representatives to further enhance Auvelity's market presence. Looking ahead, Axsome anticipates significant growth driven by upcoming product launches, including AXS-07 for migraines, which is poised for FDA review by January 31, 2025. The organization remains steadfast in targeting cash flow positivity in the near future.

Strong Financial Performance in Q3 2024

Axsome Therapeutics reported a remarkable milestone in the third quarter of 2024, generating over $100 million in product revenue for the first time. This substantial revenue marks an annualized run rate of approximately $420 million, demonstrating impressive growth just two years into their commercial operations. The company continues to focus on its mission to deliver innovative central nervous system drugs, aiming to make a significant impact on over 150 million patients in the U.S.

Robust Sales Growth of Auvelity

Auvelity demonstrated exceptional sales performance, with around 144,000 prescriptions filled in Q3, reflecting an impressive 108% year-over-year growth and a 17% increase from the previous quarter. This surge in prescriptions can be attributed to the expansion of market access, as coverage for Auvelity improved significantly, now encompassing 63% of commercial lives and 78% of total lives. This growth suggests a strengthening foothold in the psychiatric market.

Strategic Commercial Expansion

To capitalize on the momentum, Axsome plans to expand its Auvelity sales force to approximately 300 representatives by the first quarter of 2025. The expected increase in 'share of voice' will leverage recent market access wins and product differentiation in a competitive landscape, thus positioning Auvelity for further growth heading into the next year.

Sunosi Continues to Grow

Sunosi, aimed at treating excessive daytime sleepiness, also showed positive performance with total prescriptions reaching about 47,000 in Q3—a growth of 15% year-over-year and 5% from the previous quarter. The sales team successfully activated more than 4,100 new patients during the same period, indicating strong demand and depth of engagement with prescribers.

Pipeline Developments and Future Catalysts

Axsome's pipeline is rich with potential, featuring five late-stage product candidates across nine indications. A key priority is the anticipated FDA decision regarding AXS-07 for migraine treatment, with a PDUFA action date set for January 31, 2025. If approved, AXS-07's unique pharmacological profile may address significant gaps in migraine therapy.

Continued Investment and Cost Management

Research and development (R&D) expenses increased to $45.4 million for the quarter, primarily due to ongoing clinical programs. General and administrative expenses also rose to $95.6 million, reflecting sustained investments in commercialization efforts. Despite these increases, Axsome maintains a sufficient cash balance of $327.3 million, allowing them to fund operations towards achieving cash flow positivity in alignment with their strategic goals.

Long-Term Vision and Market Opportunity

Looking forward, Axsome estimates that their late-stage pipeline could generate over $16 billion in peak sales if successfully developed. The company is pleased with the depth and diversity of their portfolio and remains committed to addressing the complex needs of patients with serious CNS conditions. The management is poised to keep shareholders informed regarding developments in their innovative therapies.

Earnings Call Transcript 2024-Q3

[Operator]

Good morning, and welcome to the Axsome Therapeutics Third Quarter 2024 Financial Results Conference Call. [Operator Instructions]

Please note that today's call is being recorded. I'll now turn the call over to Darren Opland, Director of Corporate Communications. Please go ahead, sir.

[Darren Opland, executive]

Thank you. Good morning, everyone, and thank you for joining our third quarter 2024 financial results conference call. I'm joined today by Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Mark Jacobson, Chief Operating Officer; and Ari Maizel, Chief Commercial Officer.

Earlier this morning, we posted a new corporate presentation complementing today's call to the Investors section of our website. Those joining via webcast may also advance through the slides at any time during the discussion.

As a reminder, we will be making certain forward-looking statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and nonclinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development plans, our commercial plans regarding Sunosi, Auvelity and our pipeline products, revenue projections, and other financial forecasts, if any, and the possible intended use of cash and investments. These forward-looking statements are based on current information, assumptions and expectations of future events and are subject to certain risks and uncertainties that may cause the company's actual performance and results to differ materially from those projected.

Please refer to today's press release, presentation and our SEC filings for additional details on these and important risk factors. You are cautioned not to rely on these forward-looking statements, which are made only as of today's date, and the company disclaims any obligation to update or revise these statements.

With that, I'll hand it over to Herriot.

[Herriot Tabuteau, executive]

Thank you, Darren, and good morning, everyone. Thank you for joining us on today's financial results and business update conference call. At Axsome, we are focused on developing and delivering novel innovative medicines that can transform the lives of patients living with serious central nervous system conditions. We are pleased to report on the progress we've made in advancing this important mission in the quarter, articulate our long-term vision and review potentially value driving year and intermediate-term milestones.

The third quarter was another strong quarter and represented a notable milestone as we delivered quarterly product revenue in excess of $100 million for the first time. This quarterly performance translates to an annual revenue run rate of approximately $420 million, just 3 quarters into our second full year as a commercial company. While this progress is tremendous, even more significant potential growth lies ahead based on our current portfolio of innovative, marketing and late-stage pipeline candidates.

In addition to Auvelity and Sunosi, our 2 FDA-approved treatments for major depressive disorder in excessive daytime sleepiness and narcolepsy and obstructive sleep apnea, respectively. Our pipeline features 5 innovative late-stage product candidates currently in development on 9 indications across psychiatry and neurology. Our late-stage pipeline positions us to continue to deliver important new medicines in therapeutic areas that impact more than 150 million patients in the U.S. If successfully developed, this portfolio has the potential to provide over $16 billion in peak sales. The diversity and depth of our pipeline also reflects Axsome's differentiated approach to scientific innovation, which we believe aligns with our patient-centric mission and expand the therapeutic possibilities for seniors conditions.

Now before turning it over to Nick and Ari, who will provide greater detail on the strong performance in the quarter for Auvelity and Sunosi, I will provide an update on the pipeline and upcoming milestones.

A key development in the quarter was the resubmission of our new drug application for AXS-07, our novel, multi-mechanistic product candidate for the acute treatment of migraine. The resubmission was acknowledged by the FDA and designated as a Class II resolution with a PDUFA action goal date of January 31, 2025. Launch preparations are underway to ensure timely commercialization, if approved.

Our ongoing EMERGE Phase III trial evaluating [indiscernible] in patients with a prior inadequate response to oral CGRP [ antagonists ] is on track to read out in the fourth quarter of this year. Results from this trial will help inform the potential utility of AXS-07 in different patient subgroups. With respect to AXS-14 for the management of fibromyalgia, we are completing corporations for the NDA submission. We expect to submit the NDA to the FDA this month.

I'd now like to comment on our other late-stage pipeline products, starting with AXS-05. Our comprehensive development program for AXS-05 in Alzheimer's disease agitation consists of 4 pivotal Phase III placebo-controled efficacy trials, the completed positive ADVANCE-1 in quarter 1 trials and the ongoing ADVANCE-2 and ACCORD-2 trials. ADVANCE-2 is a parallel group trial and ACCORD-2 uses a randomized [indiscernible] design. Given that [indiscernible] enrollment in both trials have been reached, we are on track to report top line results from both ADVANCE-2 and ACCORD-2 simultaneously this quarter. We look forward to these readouts as we believe that a favorable outcome from one or both of these ongoing pivotal studies, in addition to the positive results from the 2 completed trials, will provide strong support for an NDA filing for AXS-05 for Alzheimer's disease agitation.

Turning now to AXS-12. We are currently conducting a 2-period Phase III trial evaluating the long-term efficacy and safety of AXS-12 in narcolepsy called the ENCORE for evaluating continued treatment with reboxetine study. The trial consists of a 24-week open-label period followed by a 3-week double-blind, randomized withdrawal period. Enrollment in the trial is complete, and we are on track to report top line results this quarter.

The ENCORE trial was conducted as a registration study to provide additional support for our planned NDA for AXS-12. Following completion of the trial, we plan to request a pre-NDA meeting with the FDA to discuss our planned submission.

Rounding out our development pipeline will continue to advance our 4 ongoing Phase III trial with [indiscernible] in ADHD, major depressive disorder MDD, binge eating disorder and shift work disorder, which we believe represents significant expansion opportunities for solriamfetol.

Enrolling in the FOCUS Study, our Phase III double-blind placebo-controlled trial, evaluating the efficacy and safety of solriamfetol in ADHD in adults is expected to complete in December, and as a result, we now anticipate top line results in the first quarter of 2025.

Additionally, the PARADIGM Phase III trial in major depressive disorder is progressing nicely, with enrollment also expected to complete this quarter. PARADIGM will examine the effect of solriamfetol in MDD patients with and without [indiscernible]. We now anticipate top line results from the trial in the first quarter of 2025.

Lastly, the ENGAGE Phase III trial in binge eating disorder and a sustained Phase III trial in shift work disorder continue to enroll with top line results anticipated in 2025 and 2026, respectively.

As we highlighted in previous calls, solriamfetol's unique pharmacology as a dopamine and norepinephrine reuptake inhibitor, and TAAR1 and 5-HT1A agonist, along with preclinical and clinical evidence, supports its potential to treat a broad range of CNS conditions, impacting over 80 million people in the U.S. With the potential new indications for solriamfetol under study, we have the potential to deliver multiple value-creating catalysts to drive long-term growth for solriamfetol alone.

In closing, the path ahead for Axsome includes a robust series of clinical, regulatory and commercial milestones. With strategic focus, operational excellence, a strong balance sheet, we are confident in our ability to deliver significant near and long-term value for patients and shareholders.

With that, I'll hand it over to Nick.

[Nick Pizzie, executive]

Thank you, Herriot. Today, I'll share our third quarter financial results and provide some financial guidance. We delivered yet another robust quarter and reported total net product revenue of $104.8 million compared to $57.8 million for the same period in 2023, representing an 81% year-over-year increase. Auvelity's strong sales momentum continued with net product sales increasing to $80.4 million in the third quarter, representing 113% growth compared to the prior year period and 24% sequential growth versus Q2 2024.

We're also pleased with the continued performance of Sunosi, which delivered net product revenue of $24.4 million in the quarter or a 21% increase compared to the same period in 2023. Gross to net was approximately 50% for Auvelity and in the low 50s for Sunosi.

Our R&D expenses for Q3 were $45.4 million compared to $28.8 million for the same period in 2023. The increase was primarily driven by our ongoing clinical programs for AXS-05 and solriamfetol as well as increased chemistry manufacturing and controls costs associated with our pipeline products, and higher personnel costs, including noncash stock-based compensation associated with organizational growth.

SG&A expenses for the third quarter were $95.6 million compared to $83.2 million for the same period in 2023. The increase was mainly a result of continued investments for the commercialization of Auvelity and Sunosi along with higher personnel costs, including noncash stock-based compensation associated with organizational growth.

Net loss for the third quarter was $64.6 million or $1.34 per share compared to $62.2 million or $1.32 per share for the comparable period in 2023. The $64.6 million loss includes $40.9 million in noncash charges, which reflects a fair market value adjustment for contingent consideration this quarter of $16.4 million.

Cash and cash equivalents totaled $327.3 million as of September 30, 2024. As we approach the potential launches of AXS-07 in migraine and other late-stage assets in the coming years, we remain committed to our principal efficient approach to capital allocation that has yielded substantial returns to date. As such, we believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity based on the current operating plan.

And with that, I'll turn the call over to Ari, Axsome's Chief Commercial Officer, to provide details on our commercial performance.

[Ari Maizel, executive]

Thank you, Nick. Axsome delivered robust commercial performance in the third quarter of 2024. In addition to strong sales performance for Auvelity and Sunosi, Q3 saw continued improvements in market access dynamics for both brands, including an increase in covered lives for Auvelity for the second consecutive quarter, reinforcing the strength and quality of our commercial execution.

Auvelity, once again, outperformed the market and branded competitors with approximately 144,000 prescriptions in the third quarter, representing 108% growth year-over-year and 17% growth sequentially compared to the second quarter. By comparison, the antidepressant market grew 1% year-over-year and sequentially. Nearly 26,000 new patients were prescribed Auvelity in this quarter, bringing the total number of new patients started on Auvelity since launch to nearly 140,000. Our sales team successfully activated more than 4,100 new prescribers in the third quarter and continue to penetrate both the psychiatry and primary care markets among [ MDs, NPs and PAs ], who care for the majority of depression patients across the U.S.

On the market access front, our previously announced expansion of covered lives for Auvelity resulted in meaningful increases in new patient starts and covered claims. Coverage continues to evolve and expand, and Auvelity now has 63% of commercial lives covered and 78% of total lives from across payer channels. Negotiations with payers and [ PBMs ] are advancing across the access landscape.

To build on the success of the Auvelity launch, we are planning a second expansion of our Auvelity psychiatry sales force to approximately 300 sales representatives, which is expected to complete in the first quarter of 2025. The increase in share of voice, combined with strength and market access, outstanding product attributes and positive provider and patient experiences with Auvelity will position the brand for further growth as we enter another pivotal year for Axsome.

Turning to Sunosi. Total prescriptions were approximately 47,000 in the quarter, representing 15% year-over-year growth and 5% sequential growth. By comparison, the [ weight ] promoting agent market grew 3% year-over-year and 4% sequentially. Sunosi's strong performance with new patient prescriptions once again in Q3, with more than 4,100 new patients initiating Sunosi treatment during the quarter as the Sunosi team continues to drive depth with existing prescribers while also activating approximately 400 new [ writers ] in the quarter.

Turning now to AXS-07. As Herriot mentioned in his open, we are eagerly anticipating the January 31 PDUFA date for this innovative treatment. Migraine is the leading cause of disability among neurological disorders and affects approximately 39 million Americans, 70% of them report not being fully satisfied with their current treatment due to suboptimal efficacy.

If approved, AXS-07's distinct multi-mechanistic pharmacology has the potential to address this unmet need. Launch preparations are well underway, including the build-out of the AXS-07 sales team. We anticipate a commercial launch in the first half of 2025.

In closing, we have made significant progress in 2024, our second full year as a commercial company and have firmly established Axsome as a trusted partner for providers, patients and payers, providing a solid foundation for continued commercial performance for Auvelity and Sunosi as well as future product launches.

I will now turn the call back to Darren for Q&A.

[Darren Opland, executive]

Thanks, Ari. I'll now turn it over to the operator to begin the Q&A.

[Operator]

[Operator Instructions] Our first question comes from Vikram Purohit with Morgan Stanley.

[Unknown Analyst]

This is Morgan on for Vikram. So on the Auvelity sales force expansion, how long would you expect this full expansion to take? And how much of a sales lift would you expect from the expansion? And then I have a follow-up after that.

[Ari Maizel, executive]

Morgan, this is Ari. Thanks for the question. As we mentioned, we expect the expansion to be completed in the first quarter of next year. In terms of lift, I would suggest that our last expansion, the guidance we gave was that the ramp would build over the course of the year. I think you saw as we completed that expansion in January of this year, we started to see the impact straight away, and it's been part of the reason why the brand has performed so well over the course of this year. So we would expect a similar impact for the second expansion.

[Unknown Analyst]

Okay. That's helpful. And then would you say -- how much of this move would be driven by the desire to expand in MDD versus preparation for potential ADA launch as well?

[Ari Maizel, executive]

Yes. This is really about MDD, and the rationale for it, recent market access wins have expanded the potential for Auvelity as first or second-line treatment. We've also seen promising growth in the primary care market. We expect further improvements in market access moving forward and continued growth in primary care. So this makes sense to capitalize on those dynamics. But to your point, we do see potential synergy for the future if ADA is approved. And so we'll share more updates on that at the appropriate time.

[Operator]

Our next question comes from Jason Gerberry with Bank of America.

[Jason Gerberry, analyst]

First, just on Auvelity. Curious your thoughts on new atypical antipsychotics that are likely to be approved next year as [ adjunctive. ] I get that these are technically considered different segments of the market, but is it fair to think that the target patient that might be an option for a new monotherapy with a different mechanism versus considering going on to [ adjunctive, ] there's sort of a competitive tension there. So I'm just wondering if there's new any way atypical like [indiscernible] with a better tolerability profile might be somewhat of a competitor to Auvelity.That's my first question.

And then just as a follow-up. On the ADA marketplace, I know in the past, you guys have said, you feel like you have a differentiated profile. So whatever we're seeing with Rexulti may not be applicable to an eventual Auvelity launch. But I guess the one thing we've heard is a big issue has been high out-of-pocket costs for patients because it's a high Medicare SKU. Sponsors are really able to defray those costs through co-pay assistance program. So how do you overcome that hurdle, which seems more intrinsic to the ADA marketplace? That's my follow-up.

[Unknown Executive]

Great. Yes, thanks, Jason, for the questions. I'll start with the atypical question. Obviously, adjunctive [indiscernible] is slightly different than monotherapy [indiscernible]. And although there is use of atypical in addition to monotherapies, we do see these as distinct marketplaces. As we've stated previously, we firmly believe that Auvelity is a first or second line treatment. Typically, atypicals will come into play in a later line, third or fourth when the patient has had inadequate response to monotherapy treatments.

Your comment about capitalized tolerability profile, I believe, is related to other atypicals because our safety tolerability profile, I would say, is very strong in this marketplace. So while we expect there to be some level of noise, ultimately, we believe our key competitive set is with monotherapy SSRI, SNRIs, and that's how we're commercializing the product.

As it relates to ADA, we have been following the Rexulti launch very carefully. And I think for any branded agent on the marketplace, out-of-pocket expense is always a tough concern for providers and patients. Part of our strategy is we continue to develop strong working relationships with payers and [ PBMs ] across the landscape as we develop those relationships and expand coverage for Auvelity and Sunosi. We expect there to be a benefit for the ADA launch, which should set us up to help mitigate out-of-pocket expenses for those patients over time.

[Jason Gerberry, analyst]

So you guys wouldn't expect to have [ $200 ] out-of-pocket kind of co-pay costs borne on these patients?

[Unknown Executive]

Jason, it really depends on the coverage and the rebate agreements that we have with the plan. So it's a little premature to comment exactly on the out-of-pocket expense. But our goal is to ensure that there's access for every patient. And that out-of-pocket expenses, it's managed appropriately.

[Operator]

Our next question comes from Leonid Timashev with RBC Capital Markets.

[Leonid Timashev, analyst]

It's Leo. Congratulations on the quarter. Just a simple one from me, I guess. On ADA, I guess, now that you reached target enrollment in both ADVANCE-2 and ACCORD-2, can you talk about both how the patients you've enrolled in ADVANCE-2 compared to ADVANCE-1 and what your expectations would have been? And then also the event rate for ACCORD-2 compared to your expectations?

[Herriot Tabuteau, executive]

Sure. Thank you for the question. So as you mentioned, we have reached target enrollment. As it relates to the patient population, they're very similar. So you we do an exclusive criteria for the ADVANCE-1 and ADVANCE-2 studies are very similar. And I would say the same thing with regards to ACCORD-1 and ACCORD-2. The goal was to make ADVANCE-2 as well as ACCORD-2 replicative studies.

As it relates to the event rates, the event rates are what we're expecting them to be. And that is why we're confident that we will be able to have a readout this quarter for both the ACCORD-2 study as all the ADVANCE-2 study simultaneously.

[Operator]

Our next question comes from Charles Duncan with Cantor Fitzgerald.

[Charles Duncan, analyst]

Herriot and team, congrats on a nice quarter. And I appreciate all the color on the pipeline, lots going on. I had a couple of questions. One is kind of commercial on AXS-05 and then a follow-up in terms of the pipeline and its upcoming readouts. With regard to Auvelity, are you getting more traction with psychs or [ PCPs ], and is the rapidity of response a driver to that? And do you think that, that profile could read on potential differentiation relative to, say, Rexulti, if the drug shows effects and is approved for ADA?

[Ari Maizel, executive]

Charles, this is Ari. Thanks so much for the question. To answer your question, we're doing quite well in both the psychiatry and primary care market. That said, in Q3, primary care clinicians were the fastest-growing segment, which is a really great signal. Something we talked about historically that we expect that segment of the market to continue to grow. So we're really pleased with the progress that we're making in the primary care segment.

Your comment about rapid acting is spot on. It is one the top drivers of utilization in the depression market. And yes, based on our early conversations with KOLs in the Alzheimer's education market, that rapidity of response is a very compelling attribute that we think will be a core part of our brand story at launch.

[Charles Duncan, analyst]

Helpful, Ari. Relative to the upcoming AXS-05 readout, looks like ADVANCE-2 is slightly smaller sample size than ADVANCE-1. So does that make you at all concerned about what you might observe there in terms of effect size? And then can you provide us any color on the ongoing open-label extension study in terms of enrollment or rollover into that and then persistence?

[Herriot Tabuteau, executive]

Great. So with regards to the sample size for ADVANCE-2, Charles. So the sample sizes that you see in our slide presentation, these are our target enrollment numbers. And the numbers always differ slightly once you actually complete enrollment. You never reach the exact numbers. You might -- usually, it's plus or minus. So I wouldn't read too much into that except to look at that number and use it as a guide to how the study is powered.

In terms of the open-label expansion, we've seen a very nice or very high percentage of patients rolling over from the control study, those in the open-label extension studies or the open-label extension study. And usually, that's a positive sign in terms of how patients and caregivers precede a product. So we're very happy to see that. Another benefit of a high enrollment rate in the open-label safety extension studies is that it does allow us to move towards our target exposure numbers, which are needed from an [ ICA ] perspective to enable an NDA filing. And on that front, we're very well positioned.

[Operator]

Our next question comes from Cerena Chen with Wells Fargo.

[Cerena Chen, analyst]

Congrats on a strong quarter. I want to ask about solriamfetol in ADHD with the FOCUS study now pushed out to 1Q '25. I was just wondering if there is any kind of slowdown or competition and -- sorry, in enrollment. And then what is your thinking on running the pediatric study? Are you still planning to start that prior to or potentially after the adult data readout?

[Mark Jacobson, executive]

This is Mark. So with respect to timing, that's simply the final screening funnel and kind of what we're seeing. So the study is already over 95% enrolled, it's just our final estimate of how long final patient enrollment is going to take. So stay tuned. And that's all moving along. And then with respect to the pediatric study, those plans are in the works and we're going to launch that as -- basically as soon as we're able. And so also stay tuned for that. But it's not predicated on the FOCUS study per se.

[Operator]

Our next question comes from David Amsellem with Piper Sandler.

[David Amsellem, analyst]

So wanted to ask about the cost structure broadly speaking. And I know I'm not asking for any sort of guidance question about 2025. But I did want to drill down on how you're thinking about R&D spend, not just for next year, but as you think beyond that, particularly with a lot of programs, a lot of studies wrapping up next year. How should we think about that?

And then secondly, regarding promotional spend. I mean I know you have the expansion of the sales force in support of Auvelity. But how are you thinking about, say, migraine and then Alzheimer's and the extent to which you're going to be adding head count to support these additional opportunities. Help us understand how SG&A is going to expand next year and beyond.

[Herriot Tabuteau, executive]

Maybe I'll just give just some overarching comments and then I'll let the other members of the team provide more detail. But just overall, the way that we've thought about spending in terms of -- whether it's for R&D or for commercialization is to approach it in a very rational way. So there is an intense focus in the company culturally on return on invested capital. So everything that we do will be very well thought out and will be done in a rational way. Now that may differ from what maybe we're used to seeing with other companies. However, we think that that's the right way to run the business.

[Nick Pizzie, executive]

Sure. Yes. And maybe just -- David, this is Nick. And just to add on to Herriot, I think he made the key points. But we, at Axsome right now, at the end of Q3, are in the strongest capital position that I'd say we've ever been since inception. As a reminder, with our current cash on hand, we have the ability to get to cash flow positivity and execute on all of our priorities that are in our operating plans, including further investing in Auvelity, Sunosi, the launch of AXS-07 and just furthering our pipeline.

And then just maybe specifically on this quarter, in Q4 and how we should think about OpEx in Q4. We saw Q3, we were -- we had a decrease in R&D and SG&A from the previous quarter. We would expect a slight increase in Q4 as it relates to our R&D spend. And that's mainly due to the PDUFA fit for AXS-14. So we're following that shortly. And then SG&A, again, potentially slightly increasing just as we prepare for the migraine launch.

[Operator]

Our next question comes from Marc Goodman with Leerink.

[Marc Goodman, analyst]

First of all, on Auvelity, can you just give us a sense of how the product is being used and how that's evolving?

Second question is the expansion in the sales force, that's just for Auvelity. But how are the reps going to be used for the migraine launch? I know the question has been asked a few times, but just -- I'll ask it again, like are we going to have another expansion for the migraine when it's approved? Or are we going to leverage these reps that you're about to add?

And then just lastly on reboxetine. Can you just give us an update on what you need to file this product? You're running another study, you have the positive study. So do you need this study to be positive to file? Are we looking for more patients for long-term safety? Just curious what the gating issue there is.

[Ari Maizel, executive]

Mark, it's Ari. I'll start with the Auvelity utilization. So we, again, saw an incremental increase in first and second line use. It remains around 50% first or second line use in Q3. So pleased with sort of the incremental growth, and we expect that to continue to build, particularly as we bring more market access online for the product. In addition, when you think about monotherapy or [ adjunctive ] use, again, we saw an increase in monotherapy use, but it remains around 50% monotherapy adjunct. So overall, the trends are in line with our expectations and we expect that to continue to improve over time.

As it relates to the expansion, this expansion is for Auvelity [indiscernible]. When you think about the migraine launch, we do intend to enter the migraine market in a targeted differentiated way that leverages our experience with Auvelity. So there will be an additional expansion, if you will, of sales representatives. I would say that we've made significant progress over the past year with our digital-centric commercialization model. We expect 07 to benefit from this experience at launch, but we will be engaging with top migraine treaters and headache centers, large neurology clinics, et cetera. So we'll share additional details as we get a little bit closer.

[Herriot Tabuteau, executive]

Great. As it relates to the reboxetine question. So Mark, I think what you're referring to is our ENCORE trial. This is the Phase III trial in patients with narcolepsy. So we do not need this study to be positive in order to be able to file an NDA. So we already have our 2 studies, which will support the efficacy claims that we want to make with regards to reboxetine or AXS-12.

However, the Phase III trial, the long term -- the Phase III long-term safety extension trial, it does incorporate a 3-week randomized withdrawal period. So that's always been the design of the study from the very beginning. And it's just that there has not been much focus on it. So as we near the readout for that study, we did want to point out that this is, in fact, a controlled study, and it should provide additional efficacy data. And if it's positive, that's fantastic, it will make for an even stronger package.

[Marc Goodman, analyst]

But you're filing anyway with or without a positive study?

[Herriot Tabuteau, executive]

Correct. And the ENCORE study, it has 2 periods. One is the open-label period. That's a 6-month open-label safety extension trial. So that was the original reason for running the study. So we do leave that part of the study in order to file. And then using our strategy that we've used in the past, which is to make sure that we're efficient in everything that we do, when we designed the study, we did include a [indiscernible] phase, which is AXS-12 versus placebo.

[Operator]

Our next question comes from Joseph Thome with TD Cowen & Company.

[Joseph Thome, analyst]

Congrats on the progress. Maybe first one on solriamfetol in MDD. I guess given sort of the high bar that Auvelity has set in the indication, what sort of the area for differentiation that you're looking for here to consider additional investment on that program? And then second, when you're thinking about the enrollment of AXS-05 in Alzheimer's agitation, where are you finding these patients? What sort of the last touch point before being referred into the study? Is it a neuro psychiatrist? Is it an Alzheimer's physician? Is it a primary care doctor? Kind of where can we find these patients? And is it different in the commercial setting?

[Herriot Tabuteau, executive]

Great. So thank you for the question. As it relates to solriamfetol in major depressive disorders, so we are studying solriamfetol in patients with MDD, both with and without excessive daytime sleepiness. So if you look at the drug from a pharmacology perspective, it has a novel mechanism of action, which is [indiscernible] receptor agonist. That will provide the marketplace and clinicians and patients, a brand-new mechanism of action in MDD, and given that MDD is a very [ pararogenous ] patient population. To have different mechanisms of action is very useful. And we've seen that firsthand with Auvelity, with its novel mechanism of action and how that has been received by the marketplace.

As it relates to other points of differentiation. One of the aspects, one of the clinical aspects of major depressive disorder is its association and comorbidity with excessive daytime sleepiness. So that is one of the areas that we will look to explore in the PARADIGM study. So stay tuned. And we're looking forward very much to learnings from that study, about the potential profile of solriamfetol in MDD.

And the other question which you asked related to Alzheimer's disease agitation and where those patients are coming from. The way that clinical studies are run is we and other companies partner with critical trial centers that specialize in psychiatry. So the way that clinical trial enrollment works is not to go specifically to the general population, although there is advertising. It is to go to centers that have experience and relationships in taking care of these patients and enrolling them. So that's where the patients are coming from.

And as it relates to how that might translate into commercialization, I think one point of differentiation with our program is that it is focused on community dwelling patients. So these are not your [indiscernible] patients. And one of the potential benefits of AXS-05 in Alzheimer's disease agitation should be successfully developed is, in fact, to keep patients out of the nursing home.

[Operator]

Our next question comes from Joon Lee with Truist Securities.

[Unknown Analyst]

This is [indiscernible] on for Joon. Congrats on the quarter. The first question for me is, can you remind us what the powering FX side of the ADVANCE-2 study is? And then as a follow-up on Auvelity, have you seen some sort of inflection from the increased coverage of 22 million additional new lives on August 1? Or would you say you're seeing more than inflection due to the sales force expansion from earlier this year?

[Herriot Tabuteau, executive]

Well, ADVANCE-2 is powered very similarly to ADVANCE-1, so it's 90% powered to detect a treatment difference. We have not talked about exactly what the [ effect ] size is, but the effect size that it's powered to detect is similar to the effect size in ADVANCE-1.

[Unknown Executive]

And thanks for the question on Auvelity inflection. We are very pleased with the demand that we've driven post the market access expansion. We have seen meaningful growth in both new patient starts and covered claims. In addition, we've seen a reduction in rejection rates for those covered lives. So overall, we're very pleased with the performance. I think keep in mind that, that win occurred during the summer seasonality month. So we expect that to continue to build over time. And so I don't think it's a fair comparison to say which created more inflection. But given the fact that the expansion -- the sales force expansion was earlier in the year has obviously had more time to make impact, and we've been very pleased with the impact we've seen over the course of the year.

[Operator]

Our next question comes from Myles Minter with William Blair.

[Myles Minter, analyst]

Just back on the sales force expansion. I know you've still got one large [ GPO ] contract that you could potentially execute here. Is that 300 sales force expansion next year incorporating that you get that? Or is it more from the level of access that you have now, you think that, that expansion is required? And if you bring on another GPO contract, we could get a further expansion?

And then just secondly, on AXS-14, have you started to engage payers and is that sort of unique benefit on fatigue that you might see with that age and something that jives with them potentially having a cover of branded therapy price?

[Unknown Executive]

Myles, so regarding the sales force expansion, it's not specifically tied to a future market access win. It's really to capitalize on the market access we have today and sort of the increase in first and second line access that we've experienced this year. But also the growth we've seen in primary care in 2024 are 2 of the primary reasons why we believe it was the right time to add additional selling efforts. So any additional market access wins would be additive to this expansion and further accelerate performance.

[Herriot Tabuteau, executive]

Yes. And you asked a question about whether or not we start to engage with payers as it relates to AXS-14.

[Unknown Executive]

Yes. So we do talk to payers regarding our pipeline, generally speaking. And obviously, the things that are more near term to launch are of more interest as it relates to sort of payer or rebate negotiation. That said, I think it's fair to say that payers are very impressed with the breadth of our portfolio. They've recognized that these are areas of significant unmet need. And although there are existing treatment options, there's still plenty of room to improve on not only symptom improvement, quality of life, but also health resource utilization. And so we feel very good about the strength of the profile of 14 and others and believe we'll have constructive negotiations once we get closer to launch.

[Mark Jacobson, executive]

And Myles, this is Mark. Just to your observation on fatigue in particular, we do think that is an important element of the product profile.

[Operator]

Our next question is from Yatin Suneja with Guggenheim Partners.

[Eddie Hickman, analyst]

This is Eddie on for Yatin. Congrats on the quarter. For Auvelity, what sense are you getting from the real-world rate of discontinuation, especially as it relates to the pivotal studies and other sort of branded antidepressants on the market. And then in terms of the coverage, it looks like you're creeping up in terms of commercial coverage, but what are the major hurdles you're seeing to getting broader coverage access on that commercial channel beyond that sort of 60% to 65% range?

[Unknown Executive]

Yes. Thanks for the question. Regarding discontinuation, we haven't seen anything significant over the course of this year. And in fact, the persistency that we've observed has been very positive. In fact, one of our internal analysis suggests that Auvelity persistence outpaced that of SSRIs and SNRIs. So we're really pleased with that, and there's been no impact from the ongoing clinical trials in the marketplace.

In terms of hurdles, it's really about aligning on final rebates and utilization management criteria with the outstanding plans. And we're very confident in the negotiations that we've had and expect to see access expand and evolve in the near term.

[Operator]

Our next question comes from Ami Fadia with Needham Co.

[Unknown Analyst]

This is [indiscernible] for Ami. My first question is, how do you [ expect ] the prescription trends for Auvelity to differ in fourth quarter with the number of holidays? And could you provide us some additional color on the timing of the data readouts expected in the fourth quarter for Alzheimer's disease agitation and migraine?

And lastly, does the EMERGE study in any way impact the regulatory decision on Jan. 31?

[Ari Maizel, executive]

Ami, this is Ari. I'll start with the demand question. So we do expect there will be some impact from seasonality in Q4. Quantifying that is a little difficult at this time. I would point to Q3, which also there's a seasonality effect and Auvelity outpaced the market, both the generic and branded market, which in both cases. And so we feel optimistic that we'll be able to continue to grow the brand, but we do expect some seasonality impact in Q4.

[Herriot Tabuteau, executive]

With respect to cadence of the readout -- excuse me, between now and the end of the year, that's right around the corner. So I think you can stay tuned for that and we haven't -- we're not -- this morning, we didn't provide guidance on the exact choreography, but again, it's right around the corner, and we're looking forward to providing updates there.

And then with respect to EMERGE, I think I heard the question is, is that needed for the NDA submission or resubmission or from a regulatory perspective. And so just as a reminder that the AXS-07 trial that will read out, and that is not needed from a regulatory perspective. Instead, we expect that to -- whatever we learn from that, we'll inform potential approaching the marketplace and medical and potential commercial communications.

[Operator]

Our next question comes from Joel Beatty with Baird.

[Joel Beatty, analyst]

First question is for the sales force expansion, how much more reach does that give you? Like, for example, how many more [ docs ] does that allow you to cover? And then the second question is for ADA, when would you expect to be able to file?

[Unknown Executive]

Yes. Thanks, Joel, for the question. There will be some increase in reach. But I think importantly, there's also a frequency play here for high decile providers. And so we feel really good about the markets in which we're expanding capitalizing on the strong market access in those markets. And ultimately think that it will be sort of a dual benefit in getting in front of more doctors. And I have a specific number for you at the moment, but also frequenting those doctors more regularly.

[Herriot Tabuteau, executive]

Great. And as it relates to timing of filing for the Alzheimer's disease agitation, the choreography is that once we have the readout from the ongoing studies, we will then see [indiscernible] pre-NDA meeting. But in general, the way that we think about it is it takes roughly 6 to 9 months after completing the studies in order to get a package ready for filing.

[Operator]

Our next question comes from Graig Suvannavejh with Mizuho Securities.

[Graig Suvannavejh, analyst]

Congrats on the progress in the quarter. My question is primarily on AXS-05 and AD agitation. Could you please provide your, I guess, take on the various potential Phase III AD agitation trial outcomes? In other words, I think you said earlier that you feel like hitting on either 1 of the 2 would be sufficient to support a filing. But of the 2 trials, if you're going to only hit on one, how should we think about a positive ADVANCE-2 enabled filing versus an ACCORD-2 enabled [ S&D ] filing? And then I've got a follow-up, please.

[Herriot Tabuteau, executive]

Well, thanks for your question. So just as a reminder, the program consists of 4 pivotal studies. And we've already read out 2 of those studies, which are positive. So going into these 2 readouts, there are 2 possibilities. And well, there are several possibilities. But one possibility is that both studies are positive. In other words, ACCORD-2 and ADVANCE-2 or that one of those studies is positive. In either of those situations, that would leave us with 3 or more positive efficacy trials to support an NDA filing. And that is more than is needed from a regulatory statutory perspective. So we feel really good going to these data readouts.

What we like about the program and the fact that we have 4 studies is that it will provide a lot of information in terms of the product profile and also in terms of the safety profile of the product in this population.

[Graig Suvannavejh, analyst]

Okay. And then maybe if I could just ask the gross to net. I think it was 50% for Auvelity in the third quarter. I might have missed comments around the expectation for the fourth quarter. But any comments just on fourth quarter and perhaps looking into 2025 specifically on the Auvelity gross to net?

[Nick Pizzie, executive]

Sure, Graig. It's Nick. Yes, you're correct. Auvelity [ GTN ] in the quarter was approximately 50%. That was a slight improvement from the low to mid-50s in the previous quarters. We would expect it to remain in that approximately 50% range to slightly worsening for the fourth quarter, similar to prior year. And then for 2025, we would anticipate that similar negative seasonality impact in Q1 that we've seen in previous years and the rest of the pharma industry sees, typically, and that's due to the reset of the deductibles. And we would expect that to improve throughout the year, similar again to previous years.

[Operator]

It appears we have time for 2 more questions. Our first question comes from Ram Selvaraju with H.C. Wainwright.

[Unknown Analyst]

This is [ Eduardo ] on for Ram. I had a question regarding the fibromyalgia asset. And specifically, if you were expecting to hire a [indiscernible] sales force to promote the sales of that, if it were approved? And also if you could give a little color to the binge eating disorder market and the nature of the competitive landscape in that indication.

[Unknown Executive]

Yes. So I'll start with the AXS-14 question. The fibromyalgia market is represented by a broad group of prescribers across primary care, rheumatology and team specialists. And similar to my comments about 07, we intend to market -- enter the market in a targeted differentiated way that really leverages the experience we've seen with Auvelity.

Right now, I think it's fair to say that there will likely be some distinct selling, particularly in those specialties where we don't currently call on. But in primary care, which is a large segment of the provider group, there is potential for synergy with our existing sales force. And so we'll share additional details as we get a little bit closer to launch.

[Herriot Tabuteau, executive]

Yes. As it relates to -- great. As it relates to binge eating disorder and the market for that, this is a very large patient population. There are 7 million patients in the U.S. who have binge eating disorder. And there's only one product that is currently approved. And so that's [indiscernible]. So we think that there's a lot of clinical needs and a lot of opportunity to respond to that clinical need with solriamfetol should it be successfully developed.

[Unknown Analyst]

Great. And if I could have just one last one. If you had any data or background on how Sunosi is doing outside of the U.S.?

[Nick Pizzie, executive]

Sure. Yes, Sunosi continues to perform well outside the U.S. We do outlined the royalty revenue that we received from Pharmanovia, and you'll be able to see that that's been increasing over the last couple of quarters as it's been a further prioritized at Pharmanovia in the European countries.

[Operator]

Our last question today comes from Matt Kaplan with Ladenburg Thalmann.

[Matthew Kaplan, analyst]

Just with the ADA data readout in the near term. What are -- what's your current thinking in terms of the launch plans with respect to filing AXS-05 as Auvelity or as a new brand in the ADA market?

[Herriot Tabuteau, executive]

Thanks, Matt, for the question. So the nice thing about the AXS-05 [indiscernible] application is we do have the ability to file it as an NDA under various forms, either an FDA or its freestanding NDA. And there are benefits to each approach. We are still exploring the approach that we will take. Stay tuned for that. However, what we can tell you is that it will be a very well thought-out decision.

[Operator]

We have reached the end of our question-and-answer session. And I would now like to turn the floor back over to Herriot Tabuteau closing comments.

[Herriot Tabuteau, executive]

Well, thank you again for joining us on the conference call today. Axsome has built a singular, innovative, late-stage neuroscience portfolio, spanning multiple indications in both psychiatry and neurology, which has the potential to deliver differentiated outcomes for millions of patients and compelling returns to shareholders. We look forward to keeping you posted on our progress.

[Operator]

This concludes today's teleconference. Thank you for your participation. You may disconnect your lines at this time.