Is this late in the second half of the year? And just to confirm that this new study that you’re talking about here, this is just patients who’ve already gone through that open-label. So, it’s not really competing against it at all, right? Thanks.
Nick Pizzie: Hey Marc, it’s Nick. So, for inventory, inventory remains in channel at two weeks. So, nothing has changed specifically around inventory for Auvelity nor Sunosi remains continuing at two weeks. And then, the Auvelity GTN discount for Q1 was in the low- to mid-50%s. And Sunosi GTN discount was in the mid-50%s for the quarter. As you know, Q1 typically does have a seasonality — a negative seasonality effect on GTN, which we both saw in Auvelity and Sunosi versus the prior quarter. For Auvelity, GTN did fluctuate in Q1 and ended the quarter with March being in the mid-50%s. And right now we have no reason to expect it to vary significantly from that level moving forward.
Herriot Tabuteau: And Marc, as it relates to the questions around Alzheimer’s disease agitation, so starting with ADVANCE-2, the guidance is second half of this year. We’re very comfortable. We remain very comfortable with that guidance based on enrollment trends. So, what we’re seeing is very positive with regards to how that study is proceeding. And then, as it relates to ACCORD-2, it is not competing with ADVANCE-2. So, you are correct, so you have a large number of patients who are in the open-label portion who are experiencing stable responses. So that allows us very efficiently to enroll ACCORD-2. So, we do expect for enrollment in ACCORD-2 to complete in mid-year, and the reason for the confidence around that is that the study is very far along in terms of enrollment.
Marc Goodman: And so, just to understand, for ADVANCE-2, enrollment really picked up over the past three months and that’s why you’re confident?
Herriot Tabuteau: So, we’re confident based on where enrollment was and has been. Enrollment in ADVANCE-2 is also very far along, and it continues to enroll at a predictable pace.
Marc Goodman: Okay. Thanks.
Operator: Our next question comes from David Amsellem with Piper Sandler. Please proceed with your question.
David Amsellem: I have a couple of questions on the pipeline. First, for reboxetine in narcolepsy, can you just remind us of the path forward? In other words, are you expecting to file after you’ve completed the extension, or are there any other gating items to an NDA filing? So, can you talk about that and your timeline to a filing on reboxetine in narcolepsy/cataplexy? And then, solriamfetol, can you talk to your pediatric ADHD study plan? I believe that’s a gating item to a filing in ADHD. So, it would be helpful to talk to that. And then lastly, esreboxetine in fibromyalgia, how big of a commercial priority is that? And what’s the extent to which you’re going to need to expand the commercial organization to support that product commercially? Thank you.
Herriot Tabuteau: Thank you for those questions. So, I’ll take the first two on the AXS-12 and solriamfetol, and then I’ll let Ari comment on esreboxetine. So, in terms of the timing for NDA filing for AXS-12, so the gating factor is completion of the open-label safety extension trial, which we expect to complete in the second half of this year. And then, it’ll take us then some time to put together the NDA filing, but that is the gating factor. So, once that study is completed, we will then be able to file the NDA. As it relates to solriamfetol and the pediatric ADHD study plan, you are correct that, that is a trial which needs to be part of the initial NDA package. And we’ve been working on that, as you can imagine in terms of speaking with the FDA to get that in place. And we have not yet provided precise guidance. But this is a study that we will be targeting to start this year. And with regards to esreboxetine?
Ari Maizel: Yeah, thanks for the question. I think for AXS-14 in fibromyalgia, we do view this as a meaningful commercial opportunity. There are three approved agents, but there’s a lot of room for improvement in terms of the overall clinical profile for patients. And we feel very optimistic about the profile AXS-14 offers for patients. As it relates to how it will impact the sort of commercial footprint, part of what we’re analyzing this year is how to effectively size and structure our sales force to accommodate a growing portfolio of products. Although fibromyalgia is not a psychiatric product, there is a lot of overlapping comorbidity with major depressive disorder that will influence some of our thinking. And so, it’s a little too early to say how many additional reps we would want to build into the plan or how we would structure it.
But we do think that there’s a way to promote AXS-14 efficiently while also putting plenty of attention on the other approved products on the market.
David Amsellem: That’s helpful. Thank you.
Operator: Our next question comes from Yatin Suneja with Guggenheim Partners. Please proceed with your question.
Yatin Suneja: Hey, guys. Thank you for taking my question. I have two quick ones. One is the clarification one. With regard to the ACCORD-2 study, so that’s a new study, and this is the fourth study within the ADA umbrella. Is that a requirement from the FDA that you have to do two randomized withdrawal study? And then, will the NDA package be contingent upon completion of that study or the outcome of that study? So that’s one. And then, with regard to Auvelity, I mean, very nice quarter, so congrats on that. Any thoughts on thinking about providing guidance for the product, maybe on a quarterly or on a yearly basis? Thank you.
Nick Pizzie: Yeah. Sure. Hey, Yatin, thanks for the question. It’s Nick. It’s just too early in Axsome and Auvelity’s lifecycle to provide sales guidance given the fluid nature of some of the market dynamics and the unpredictability of external factors that could have different impacts. We have shared that we believe peak sales for Auvelity and MDD alone are in the $1 billion to $3 billion range, and Sunosi is $300 million to $500 million for its current indications.
Herriot Tabuteau: So, Yatin, with regards to ACCORD-2, this is not an FDA requirement. However, it does increase the robustness of the package, and it is a pivotal trial. So, we like that. We like having four different studies. So basically, if you think about it, ADVANCE-1 and ADVANCE-2 are two parallel group studies, and ACCORD-1 and ACCORD-2 are two randomized withdrawal studies. So, a very nice source of evidence generation with those four studies. And then, with regards to the filing, is it contingent upon completion of that study? Since it’s not required, it’s not really contingent. However, we do think that based upon where we are with enrollment of that study, we expect the study to be fully enrolled mid-year. And also timing of the relapses in the ACCORD-1 trial, which was positive, that there is the potential for that study to read out around year-end.
That’s not formal guidance, and the formal guidance will be based upon the number of relapses and the timing of relapses. But just to give you a sense of how one might think about it. So, we’re really happy with the way that we’ve been able to efficiently increase the robustness of the program for this very important product.
Operator: Our next question comes from Jason Gerberry with Bank of America. Please proceed with your question.
Jason Gerberry: Hey guys. Thanks for taking my question. So, just on ACCORD-2, so it sounds like the motivation with the study is that kind of like, think about it as a marketing study. And along those lines, is there an opportunity for you to pool ACCORD-1 and ACCORD-2, such that, I don’t know, if the data has a better chance of getting into the label given that ACCORD-1 was a really small trial? And then, you guys did mention that the cyberattack in 1Q. So, I know some of your peers had kind of indicated it wasn’t really a material impact to the number. So, can you quantify to what extent the cyberattack did affect Auvelity revenues in 1Q? Thanks.
Herriot Tabuteau: Sure. So, with regards to ACCORD-2, just to be clear, this is — it can be used for marketing, obviously, but it is a registration trial, so we like that. So, it does provide a very objective source of evidence. And as it relates to being able to pool it with ACCORD-1, the two studies because they’re similar design could definitely be combined. And that’s typically something that is done in NDA packages.
Ari Maizel: Yeah. And regarding the Change Healthcare cyberattack, the impact for Auvelity was really focused on two weeks at the end of February, beginning of March. Basically what we saw was roughly 30% to 40% impact on weekly prescriptions for those couple of weeks. During that time, we put in a number of technology optimizations and patient savings optimizations, and saw a very quick bounce back in early to mid-March for our demand trend, and it’s been stable since then, stable to growing since then. So, it’s largely behind us at this point. We don’t expect any continued disruption. And for some brands, it was more impactful just related to time and market, whether patient savings cards were tied to the Change Healthcare, so things of that nature. And so that’s why it impacted us. But it was transient in nature. We feel really good about the solutions we put into place and we’ve seen really nice growth since.
Jason Gerberry: Thank you.
Operator: Our next question comes from Joon Lee with Truist Securities. Please proceed with your question.
Joon Lee: Congrats on the strong quarter, and thanks for taking our questions. Regarding ACCORD-2, what’s the rationale behind designing it as a randomized controlled trial as opposed to a standard parallel comparative trial, which appears to have — you have quite a success in? And are the endpoints in ACCORD-2 identical to that [leads] (ph) in ACCORD-1? Thank you so much.
Herriot Tabuteau: So, thanks, Joon. You were somewhat muffled, so I’ll try and answer the question the way that I interpreted it, but not necessarily what you said. But I think the question was around ACCORD-2 and what was the rationale for the design versus other designs. So, the rationale was we wanted to take advantage already of the fact that we had a study which was treating patients in an open-label fashion and therefore would allow assessment of stable response. So, it made a lot of sense, so it — since our open-label safety extension trial is essentially the same way that all randomized withdrawal studies begin. So that was the rationale there. And in terms of the endpoint, as compared to ACCORD-1, the endpoint is identical. So, this is a way for us to be able to take the learnings from ACCORD-1 and apply them to ACCORD-2 to generate additional data.
Joon Lee: Thank you.
Operator: Our next question comes from Joel Beatty with Baird. Please proceed with your question.
Joel Beatty: Hi. Thanks for taking the questions. First one is on Auvelity. Could you provide a breakdown between uses in earlier-line and later-line therapy? And with the second large purchasing contract, could the usage in early-line therapy be impacted at all?
