Started. Thank you, everybody, for joining us again this afternoon at the Citizens Life Sciences Conference. Really excited to be joined next by Axsome Therapeutics. Axsome is a commercial-stage company focused on CNS indications. It actually has a number of approved products as well as a broad pipeline. As usual, a ton of stuff going on, both from a regulatory perspective, data that you've read out in the last couple of months, as well as actually selling products. You're joined here today by Mark Jacobson, the company's Chief Operating Officer. Mark, with that, I'll say welcome and maybe hand it over to you to give a couple of quick introductory remarks.
Great. Thanks, Jason, for having us. It's good to be at the conference. This is our first time out in a while. We reported on Monday. So far this year, there's a ton going on. It's been a really strong year so far. We're not even halfway through. Q1, $122 million net sales, $96 million of that coming from Auvelity. That's our product for major depressive disorder. That's now just two years post-launch, a little bit beyond that. Our second product, Sunosi, $25 million for the quarter. We're pleased with just the continued execution and growth on those products. Now we have three products that are approved. In January, our third product, our second fully developed internally product, is Symbravo. That's for the acute treatment of migraine with and without aura. We'll be launching that next month.
That is proceeding on track. We are excited for that. Excuse me. The final kind of finishing touches on the sales and marketing platform are in the works. We can talk about that. That will be commercially available. We are targeting for next month. If you shift to what has been going on on the development side of things, Axsome Therapeutics for Alzheimer's disease agitation, we had a pre-NDA meeting minutes that we announced, the feedback from FDA on our plan. We are on track to submit an SNDA for that program in the third quarter of this year. We had a number of data readouts. In particular, solriamfetol in ADHD, positive trial. That is the focus phase three trial in adults. Can talk about next steps there.
We had a proof of concept trial in major depressive disorder where we have a nice signal in major depressive disorder patients with individuals living with major depressive disorder with excessive daytime sleepiness. There were also results associated with Symbravo from the Emerge open label trial, phase three trial in individuals with an inadequate response to prior oral CGRP therapy. That is all just what has happened so far this year. It was just an incredible amount. We are pleased with activities year to date. There is a bunch coming up. It is a really exciting year for Axsome.
Yep, totally agree. A lot going on there. Maybe to start off with Auvelity, like you said, two years on the market now. Can you maybe speak to where you've seen the initial adoption, the kind of subsegments of the MDD market where you're getting utility?
Yeah. Initial focus in terms of detailing and engagement with potential prescribers, HCPs, starting out with psychiatrists and then now going broader into primary care. Initial use right now where things stand and we're pleased with is over 50% in first or second line, so first line or first switch. Very pleased with those numbers and the growth and how it's being used, which makes a lot of sense to us, right? The product is fast, it lasts, it's differentiated. We're pleased to see the uptake. Maybe just one note on the operational side of things, we recently expanded the sales team. It's now about 300 account managers, sales reps. That expansion was completed in the first part of, so in Q1. Now we are starting to see preliminary impact. We'd expect that to grow over time.
Got it. Okay. I think one thing you guys have done really well is securing reimbursement for the product as well. Can you maybe just give us an overview of it's never easy, right? Payers don't want to pay for anything. Just how you've ensured that patients get access and where you still think you have room to grow.
Sure. Where we have room to grow is in the commercial channel. Our expectations around steady state is the vast majority of lives will be covered. We have not guided to a specific number. What you see for the class antidepressants, a steady state is north of 80%-85% of total lives covered. That is our expectation and that work is underway. What we are seeking to do, I mentioned how it is being used already, first line first switch. That speaks to the quality of coverage that is currently in place. We would expect to continue to add lives, in particular in the commercial channel, and to evolve and improve the current coverage algorithms that are in place. Already we like where we started.
You mentioned speed of onset of activity. Patients feel better really quickly on the drug. To what extent is, I guess I'm going to ask it a different way. What's driving the selection of the drug for that frontline patient? Because it's not common for a CNS drug to be used in frontline this quickly.
Yeah. It seems to be a number of things. We talked about the rapid onset of action. That is really important. Durability. Feedback we are also getting is safety profile and the tolerability profile. You have different rates of kind of the classic AEs with typical antidepressants, weight gain, sexual dysfunction. We do not see those same rates that are historically seen and often are what lead to discontinuation in treatment adherence and compliance. I think that is another key element based on the feedback we are getting from clinicians.
Two years into the launch, you have more information now than you did on persistence.
Yes.
Can you maybe just give us an idea of what you're seeing in terms of persistence rates?
Yeah.
If there's anything that you've learned along the way that maybe can help build that.
have not, we are still monitoring what it is. Right now, qualitatively, we are seeing persistence, compliance, adherence kind of beyond what you typically see. There is still flux in it, and part of that will likely depend on how additional coverage comes online and things like that. Right now, we are pleased. We are outpacing what you typically see for the class of antidepressants, but we have not given a specific number yet. It tends to be, like, the class tends to be, say, three to six months. We like how it is being used to date and the persistence numbers that we are seeing.
Maybe if we move on to AD agitation, can you maybe just hit the high points from the phase three program, what you saw, and where you see the opportunity for the drug?
Yep. No, thanks. Obviously, we're pretty excited about that, that we completed that clinical program at the end of this past year. We have three positive trials in hand and long-term safety. Very pleased with what we saw both from an efficacy and safety perspective. In particular, we did not see signals with respect to falls in mortality. We're pleased with that. We think that's really important given it's an elderly patient population. If you're just looking ahead, the next steps, I mentioned we had pre-NDA. We shared the pre-NDA feedback from FDA. That allows us to proceed with an SNDA submission in the third quarter. That's what the package will be comprised on. Team is essentially, the data generation is done. It's building the package, right, writing the modules and assembling them.
Was there anything in particular you were looking for to get out of the pre-NDA meeting? Anything that you thought could have been something you needed to get clarity on? Or is it definitely something that you have to go through?
Sure. Yeah. Aligning on content and format, in a way, it lets the FDA know what your plans are for presentation of the data. That is good because I think in our mind, the data that we have in hand, it is a clear approach for us for the submission. You do want to align with FDA just in case there is something on their mind that you have not heard yet or you want to preview something new just to make sure that you are giving them warning too, that they have a heads up that that is coming. That is a big effort on their part. In our mind, it is a mutually beneficial interaction.
Where do you see the drug fitting in? Obviously, agitation is a symptom that develops throughout Alzheimer's as the disease progresses. I guess there are two questions here. Where do you think you'll be at launch? Where do you think you'll be down the road?
Sure.
Is it the earlier stage, get the patient as early as possible? Or are you going to end up starting with a slightly more advanced patient?
Sure. It's a huge unmet need, right? There's now one product approved. That product is growing in the space. The majority of patients are treated off label, right? The agitation is a very challenging symptom. It's often the symptom that leads to placement in long-term care facilities. It's critical to be dealt with. Clinicians, it requires intervention. Patients can be danger to themselves and others. Potentially early days, should the product be approved and launched, potential early days, you might imagine those who are already seeing clinicians may already be on some type of off-label or now on label therapy. What we love is it's differentiated mechanistically from the primary way that patients are now treated, which is atypical antipsychotics. We like that it's differentiated mechanistically. That offers very compelling elements from an efficacy and tolerability perspective.
In our work engaging with KOLs and clinicians, when we completed the clinical program, we had a call. Dr. Jeffrey Cummings participated. The feedback is such that, hey, based on the clinical profile, that's something that clinicians would envision using early in the treatment paradigm. One challenge now is there is a black box warning for the use of atypical antipsychotics in elderly individuals with dementia because of a mortality risk. That's an important consideration. A potential, obviously, we don't have a label or an approval or a label in hand, but potential differentiation there.
I think our experience is the same. Physicians hold off prescribing atypical antipsychotics for as long as they can do in Alzheimer's patients because of that safety overhang. Okay, great. Can we move on to Symbravo?
Yeah.
You said approved earlier this year.
Yeah.
You're about to launch. Just maybe start with the label. What are the key points there that you're really pleased with? How will you position the drug from day one? Maybe also let me just, how does this fit into your existing commercial infrastructure?
Sure. Great. The product is, what we like about it is differentiated. In the data, the clinical data that we generated shows robust efficacy, which is where the need is, where the patient need is. We like that a lot. What's interesting about the product is you have two rapidly acting mechanisms of action and then a very long half-life for durable symptom relief. We think that's very important. Indicated for acute treatment. It's not indicated for preventative treatment. I think that's important. When you think about detailing or the sales infrastructure around that, right now, the two facets of the Axsome sales team right now are, you can break them into psychiatry and sleep, I think, is just a simple way to do it.
We'll be adding about 100 reps to focus on the headache centers in the U.S. To us, the early days will be and beyond will be a very targeted effort to those centers. We want to drive initial trial and utilization in those centers because they tend to be where uptake begins and then expands from there for individuals with migraine. We're excited about that. We'll be announcing that in the not too distant future.
Great. Maybe could you just talk a little bit about the detailed message here? Obviously, we have newer therapies for migraine.
Yes.
Physicians have become comfortable with those therapies.
Yes.
What's the marketing focus for medical education focus?
Sure. Yeah. The team's going to be launching the marketing messages and the marketing effort and campaign soon. I won't front-run them too much. What I'll share is the need and the data we've generated is differentiated from an efficacy perspective. That is rapid relief. That is 24, 48-hour symptom relief. That is important because when you talk to folks, there's the current treatment individuals with migraine, right? This is debilitating pain. There are a bunch of treatment options. If you survey patients and clinicians, there's high, high dissatisfaction even today, despite the number of options with pain and, say, most bothersome symptom relief. The exact message we'll share with everyone soon. It will be in that vein.
Okay. Maybe let's talk about the pipeline a little bit.
Yep.
Solriamfetol, ADHD, you reported positive phase three data. You're also now showing the timeline of the efficacy curve. Can you maybe just walk us through that new data that you're now showing?
Sure. Yeah. That's the focus phase three trial that was in adults. What you're referring to, just to frame, and when we reported on Monday, we also provided an updated corporate deck. In there is the efficacy curve on the primary endpoint. That's the first time we've shared that. I mean, obviously, we top-lined the data. There wasn't an update to the deck at that time. That's there. Change in an endpoint for specific to adults with ADHD, that's AISRS and very, very robust reductions. We tested two dose levels, 150 milligrams and 300 milligrams. The primary, the key dose we were interested in is 150 milligrams. That's the highest approved dose. We are interested to see if there's a dose response or we think basically at 150 milligrams, you're capping the dose response ceiling.
Next steps here are to launch a pediatric adolescent trial. That's the second study that we need in order to file for Sunosi. What we've guided to is starting that program this year or that trial this year.
Okay. The market in adult ADHD has grown. There's definitely underdiagnosis.
Yes.
How do you ultimately see the drug being positioned there versus in the pediatric adolescent setting?
Sure. One thing just to your question that I neglected to mention, but I think that could be informative with respect to positioning and the treatment landscape, is the changes that we saw on the AISRS were very robust and in line with studies that have been done with stimulants and using the same endpoint in line with changes that you see with stimulants. That is important and compelling because then, of course, challenges with stimulants are tolerability profile, scheduling considerations, and things like that. Mechanistically, solriamfetol is differentiated from stimulants in that way, distinct scheduling. We do not see the product is approved as solriamfetol, safety and tolerability consistent with the prior clinical program. That is really compelling in terms of what is available now, stimulants, non-stimulants, which obviously have a distinct safety and tolerability profile from the stimulants.
Where we net out exactly on that spectrum is to be determined. Right now, the data we have in hand gives us—we're excited about that.
You're also now moving through a phase three trial in MDD with excessive daytime sleepiness. What's the rationale for the drug and its indication?
Sure. Yeah.
Yeah, start there.
Sure. The rationale was initially feedback from KOLs who have experience treating patients with solriamfetol and the feedback they shared about their thoughts on indications that could be interesting. The feedback was that when we acquired Sunosi, solriamfetol, we very quickly launched a broad development effort across four different indications initially. One of those was MDD. That is based on KOL feedback from mechanistic, but also real-world trial of how patients do. The study that we ran, the PARADIGM trial, we were interested to look at just overall potential impact in depression, but also with sleepiness, given what we know about the product profile already. We looked at patients with sleepiness. About 50% of patients with MDD have excessive daytime sleepiness. What we wanted to do for this study is make sure we were honing in on severe EDS.
That's what that study looked at. The next trials will be just MDD with EDS. We're planning to launch the next phase three for that program this year as well.
Got it. We said at the start there's a lot going on here.
Yes.
I want to just spend the last couple of minutes talking about a couple more NDA submissions that are now incoming. So AXS-14 and AXS-12.
Yes, thank you. Yeah.
Maybe 14 real quick. So the NDA is submitted.
Correct. Yeah.
Fibromyalgia is the indication.
Yes.
Just kind of give us the high points here, knowing that we got like a minute or two.
Sure. Okay. Yeah, very quick. It's submitted. Next step is to share potential acceptance decision from FDA. Stay tuned. Right, that's based on two randomized placebo-controlled trials, short-term trials. There are long-term data sets as well. That's one of three submissions for the year. You mentioned another. That's AXS-12. AXS-14, that's esreboxetine. That's the S enantiomer of reboxetine. AXS-12 is reboxetine. That's racemic reboxetine. We've developed for cataplexy in patients with narcolepsy. That clinical program, we completed a few months ago as well. We plan to submit an NDA for AXS-12 this year. The third, of course, we've already touched on, which is AXS-05 and AD agitation. Just on the commercial front, the clinical front, and then the regulatory front, the organization is humming across all functions.
It is a pretty exciting year for us.
Maybe just to wrap it up with a higher-level question, as you think about investors that are new to the story, a ton going on. Where do you think there still may be opportunities to pay more attention where you haven't got as much focus?
Sure. Historically, say, past 12 months and beyond, the focus has been on Auvelity and the Auvelity launch and Alzheimer's disease agitation. I think over the past few months, the rest of the organization is starting to come into focus. I think there's still much of the organization is just coming into focus. We've touched on it. We are very.
That's good service.
No, no. We are very efficient today, which is great. I think most of it is just starting to come into focus, which makes sense because obviously, some of these programs are now getting to a point where it's regulatory filings or upcoming to launch. It makes sense. That's why it's such a neat time for the company. Deep and broad foundation with all these layers that are starting to go on top.