Good morning, ladies and gentlemen, and welcome to Axsome Therapeutics' Conference Call. Currently, all participants are in a listen-only mode. We will be facilitating a question and answer session towards the end of today's call, and instructions will follow at that time. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mr. Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Please go ahead.
Thank you, operator. Good morning, everyone, thank you for joining us on today's conference call to discuss the positive top-line results from the INTERCEPT phase III trial of AXS-07 in the early treatment of migraine. A press release announcing that AXS-07 achieved the co-primary endpoints in the trial crossed the wire a short time ago and is available on our website at axsome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents, our clinical and non-clinical 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, and possible intended use of cash and investments.
These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today from Axsome's management team are Dr. Herriot Tabuteau, Chief Executive Officer, Dr. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs, Mr. Nick Pizzie, Chief Financial Officer, and Mr. Dave Marek , Chief Commercial Officer.
Herriot will start by providing an overview of today's announcement before turning the call over to Cedric, who will review in greater detail the top-line results of the INTERCEPT clinical trial. Following Cedric's presentation, we will open the line for Q&A. Herriot will close out the call with some concluding remarks. I shall now turn the call over to Herriot.
Thank you, Mark. Good morning, everyone, and thank you all for joining us on the call today. We are extremely pleased to announce that AXS-07, Axsome's novel oral multi-mechanistic investigational medicine for the acute treatment of migraine not only substantially and significantly eliminated migraine pain but importantly also substantially and significantly prevented progression of migraine pain in the INTERCEPT phase III trial of AXS-07 in the early treatment of migraine. In the study, AXS-07 met the two co-primary endpoints of freedom from migraine pain two hours after dosing with a P value of 0.002 and freedom from the most bothersome symptom two hours after dosing with a P value of 0.003. The percentage of patients achieving migraine pain freedom at two hours with AXS-07, which was 33% in this trial, is among the highest reported for any oral agent in recent studies.
The percentage of AXS-07 patients achieving freedom from most bothersome symptom at two hours was also substantial at 44%. This trial was designed such that patients were instructed to dose at the earliest onset of migraine pain while the pain was mild, which represents the anticipated real-world use of AXS-07. The results of this study demonstrate that the rapid absorption and multiple mechanisms of AXS-07 in combination with early treatment significantly prevented the progression or worsening of migraine pain beyond mild intensity. After a single dose of AXS-07, there was no progression or worsening of migraine pain in 74% of patients compared to 47% of placebo patients over 24 hours with a P value of less than 0.001.
The symptom improvement with AXS-07 translated to significant functional benefit with 74% of AXS-07 patients reporting no functional disability at 24 hours compared to 47% of placebo patients with a P value of less than 0.001. The durability and clinical meaningfulness of the effects of AXS-07 are further reflected in the substantially reduced use of rescue medication over 24 hours, which was required in only 15% of AXS-07 patients compared to 43% of placebo patients with a P value of less than 0.001. These low rates of rescue medication use are notable considering patients were treated with only one dose of AXS-07. Most pivotal trials of acute migraine treatments require patients to wait until their headache pain intensity is moderate or severe before taking study medication. However, even FDA guidance notes that dosing in this manner is contrary to what is typically recommended by migraine experts.
The INTERCEPT study was designed to replicate the anticipated real-world use of AXS-07. Therefore, these positive results are especially notable because they provide further compelling evidence of the potential of AXS-07 in the acute treatment of migraine. As a reminder, our Phase III MOMENTUM study, which reported positive results at the end of last year, was conducted in a difficult to treat patient population with a history of inadequate response to prior acute treatments. These patients were required to wait until their migraine pain was of moderate or severe intensity before dosing. With the INTERCEPT and MOMENTUM Phase III trials, AXS-07 has now been evaluated in two positive, well-controlled trials.
These studies demonstrate the efficacy of AXS-07 against both a potent active as well as against placebo comparators across a spectrum of migraine attack settings, regardless of the timing of migraine treatment, disease severity, prior treatment experience, or baseline pain intensity.
Our plan in the filing for AXS-07 in the acute treatment of migraine based on the MOMENTUM trial is strengthened by the INTERCEPT results. Our long-term open label trial of AXS-07 in migraine patients to build the safety database required for an NDA filing is on track with more than 700 patients dosed. To date, more than 1,800 patients with migraine have been dosed in our completed and ongoing trials. We are on track to file an NDA in the Q4 of this year with the goal of making AXS-07 available to patients as quickly as possible. The rest of our CNS pipeline continues to progress. In the near term, we remain on track to report top-line results from our pivotal ADVANCE phase II/III trial of AXS-05 in Alzheimer's disease agitation in early Q2. The seriousness of migraine is underappreciated.
The World Health Organization classifies severe migraine attacks as among the most disabling illnesses comparable to dementia, quadriplegia, and active psychosis. Migraine damages family life, social life, and employment. The importance of rapid and early treatment of a migraine attack is widely accepted among migraine experts. Suboptimal or prolonged time to treatment has serious consequences, as large-scale studies show that in addition to the debilitating pain, it can lead to increased progression from episodic migraine to chronic migraine. There is therefore an urgent need for new treatments that provide improved efficacy for this serious neurological disease. AXS-07 is a novel oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine consisting of MoSEIC meloxicam and rizatriptan. AXS-07 is thought to act by inhibiting CGRP release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization.
Axsome's MoSEIC technology significantly increases the speed of absorption of the meloxicam component after oral administration while maintaining a long plasma half-life. AXS-07 is covered by 27 issued U.S. and international patents, providing protection out to 2036, and Axsome maintains worldwide rights. I would now like to turn the call over to Cedric, who will review the INTERCEPT top-line results in greater detail.
Thank you, Herriot. The INTERCEPT, or Initiating Early Control of Migraine Pain and Associated Symptoms study, was a phase III randomized, double-blind, placebo-controlled, multi-center trial to assess the efficacy and safety of AXS-07 in the acute treatment of migraine. 302 patients were randomized in a one-to-one ratio to either AXS-07 or placebo and were instructed to take a single dose of study medication at the earliest onset of migraine pain when the pain was mild and before it had reached moderate or severe intensity. The co-primary endpoints of the study were pain freedom at two hours and freedom from the patient's most bothersome migraine-associated symptom, nausea, photophobia, or phonophobia at two hours for AXS-07 as compared to placebo. Secondary endpoints included sustained pain freedom from pain progression or worsening, improvement in functional disability, and the use of rescue medication. Shown here are the key entry criteria.
Eligible patients were between 18 and 65 years of age and required to have an average of two to eight migraine attacks per month. Patients were excluded if they had other headache conditions or significant cardiovascular disease. The demographics of the patients enrolled in the INTERCEPT study are representative of the migraine population. Over 85% of the subjects were female with a mean age of 41 years. There were no meaningful differences in baseline demographics across the treatment groups. All subjects reported mild migraine pain intensity at baseline prior to dosing with study drug as intended by the study design. Now to the efficacy results. On the first co-primary endpoint of pain freedom at two hours, a statistically significantly greater proportion of patients treated with AXS-07 were pain-free as compared to placebo. 32.6% versus 16.3% respectively, for a placebo-adjusted difference of 16.3% with a P value of 0.002.
On the second co-primary endpoint of freedom from the patient's most bothersome migraine-associated symptom, photophobia, phonophobia, or nausea. A statistically significantly greater proportion of patients treated with AXS-07 were free of their most bothersome symptom at two hours as compared to placebo, 43.9% versus 26.7%, respectively, for a placebo-adjusted difference of 17.3% and a P value of 0.003. AXS-07 provided rapid and substantial freedom from migraine pain, as shown on this slide. The percentage of patients achieving pain freedom with AXS-07 was numerically greater than placebo, starting at 30 minutes and statistically significant by 90 minutes. Nearly two-thirds of patients treated with AXS-07 achieved pain freedom by 12 hours. The MoSEIC meloxicam component of AXS-07 has a long half-life, which provides the robust, sustained efficacy effects seen with AXS-07.
At hour 12, the pain freedom rates were 64% for AXS-07 and 42% for placebo, with a P value of less than 0.001. At hour 24, the pain freedom rates remained high, 69% for AXS-07 and 47% for placebo, with a P value of less than 0.001. The therapeutic gain of AXS-07 improves over time, with placebo-adjusted differences in rates of pain freedom greater than 20%, starting at hour four and for every time point thereafter. Treatment with AXS-07 resulted in statistically significantly greater rates of sustained pain freedom. 22.7% of patients receiving AXS-07 who achieved pain freedom at hour two remained pain-free at hour 24, compared to 12.6% of those receiving placebo, with a P value of 0.03.
On the right side of the slide, sustained pain freedom from 2-48 hours shows similar results, with 20.5% of patients receiving AXS-07 and less than 10% of patients receiving placebo, with a P value of 0.013. These results are especially compelling as patients only received a single dose of AXS-07. Freedom from the patient's most bothersome migraine-associated symptom was numerically greater with AXS-07 at all time points measured. Statistically significant improvements were noted at hour two, the co-primary endpoint, and at hour four. Within four hours after a dose of AXS-07, over half of the subjects reported complete resolution of their most bothersome symptom. At baseline, the most common, most bothersome symptoms were photophobia, reported in 63% of subjects, followed by nausea in 21% of subjects. The ability of early treatment with AXS-07 to prevent progression or worsening of migraine pain was evaluated in the INTERCEPT trial.
In the study, patients were instructed to treat their migraine at the earliest onset of migraine pain when their pain intensity was mild. On this slide, we present the pain progression, defined as a pain intensity worse than mild or the need for rescue medication. As is shown here, AXS-07 substantially and significantly prevented migraine pain progression beyond mild. AXS-07 prevented progression of migraine in 74% of treated patients versus 47% for placebo at 24 hours with a P value of less than 0.001. The ability of AXS-07 to prevent pain progression is evidenced by the pattern of use of rescue medication, which is shown on this slide. The percentage of placebo subjects requiring rescue medication increased significantly over time, reflecting worsening pain.
In contrast, the use of rescue medication in patients treated with AXS-07 was very low and relatively unchanged over time, reflecting AXS-07's efficacy in preventing migraine pain progression. 24 hours after a single dose of AXS-07, only 15% of patients required the use of rescue medication, compared to 42% of placebo patients with a P value of less than 0.001. The efficacy of AXS-07 in entirely eliminating or halting the progression of migraine pain is beneficial in reversing the disabling symptoms of migraine and allowing a patient to return to normal functioning, as described on this slide. As shown here, 74% of patients treated with AXS-07 had no functional disability after 24 hours, compared to 47% receiving placebo with a P value of less than 0.001. The symptomatic and functional benefits of treatment with AXS-07 translated to global improvements in migraine.
On this slide, the Patient Global Impression of Change at two hours was highly statistically significant in favor of AXS-07. 52% of patients receiving AXS-07 reported very much or much improved two hours after the dose, as compared to 28% receiving placebo, with a P value of less than 0.001. AXS-07 was safe and well-tolerated in the study. The most commonly reported adverse events with AXS-07 were somnolence, dizziness, and paresthesia. There were no serious adverse events, and overall, the safety profile is consistent with that which was seen in the MOMENTUM study. In summary, in the INTERCEPT study, treatment with AXS-07 resulted in rapid, sustained, and statistically significant efficacy as compared to placebo.
Early treatment with AXS-07 resulted in substantial and significant prevention of migraine pain progression, which translated into significantly less use of rescue medication with AXS-07 as compared to placebo, and return to normal functioning in the vast majority of treated patients. Finally, AXS-07 was safe and well-tolerated in the study. We would like to thank all the patients who volunteered to participate in the INTERCEPT study. We would also like to thank all the clinical site staff who collaborated with Axsome in the execution of this important study. With that, I would like to hand the call back over to Herriot.
Thank you, Cedric. I'd like to hand it back to the operator to open the line for questions.
Certainly. At this time, if you'd like to ask a question, please press star one on your telephone keypad. To withdraw your question, press the pound key. Charles Duncan with Cantor Fitzgerald, your line is open.
Hey. Good morning, Herriot and team. Congratulations on these very good results with AXS-07. I had a couple of questions, so I appreciate you taking them. The first is regarding Cedric mentioned the reduced functional disability. Can you tell us how that was measured?
Thanks, Charles, for the question. I'll hand it over to Cedric.
Hey, Charles. Yes. The functional disability scale is one of those scales that asks you whether you have had no change in functional disability, much improved, very much improved, or worsened. It's asked at a particular time point to assess how the patient regards their level of functional ability. Coming in at baseline, you have a range of disability, and despite evaluating mild and early onset, there was quite a great degree of disability at baseline. Then at the 24-hour mark, you ask the patient to what degree they feel that they've improved.
What was compelling about these data was the fact that treating the migraine and getting those high rates of pain freedom at two hours, coupled with arresting the progression of the attack, translated very proportionally similar into patients at 24 hours saying that they were much or very much improved, 74% with AXS-07 and 47% with placebo.
Okay. you may have not yet done this.
Hey, Charles.
Yeah.
Just to clarify Cedric's response. As Cedric mentioned, we did, of course, ask patients for their level of improvement over time. That's the global measure. With regards to the actual functional disability scale, it is the same scale which has been used in other migraine studies. It's just the exact same scale that has been used by the sponsors. It actually does look at specifically whether or not somebody can perform normal daily activities or whether they have to stay in bed or whether they're incapacitated. We do measure that in the exact same way as other migraine studies that you're familiar with.
Yeah. That's helpful. I figured that it was a validated scale. You may have not done this analysis, but if so, did you detect any differences in the efficacy in the patients with most bothersome symptoms? I think about 60, well, almost two-thirds were photophobia versus nausea.
We have yet to look at those analysis when you break it out by most bothersome symptoms. What I can tell you is that 63% had photophobia at baseline and 21% had nausea at baseline.
Okay. Second question was regarding the placebo side of things. These are very nice data. It looks like the placebo activity in the control arm was relatively good compared to other recent trials. Correct me if I'm wrong if that's not the case, but what would you attribute this to? Is this due to studying patients, I think, Herriot, you mentioned earliest sign of migraine pain, or in those patients that are experienced with triptan therapy, do they have a differentiated experience with AXS-07?
I'll let Cedric comment, with regards to the placebo response rate, it's along the lines of what one would have expected in this all-comers population. It is higher than what was seen in our MOMENTUM trial. Remember, MOMENTUM was in a very refractory patient population. There, placebo response was even lower. This is along the lines of what we would've expected. It's not much greater than what we would've expected, so you're right that we were able to control the placebo response.
Charles,
Okay. I'm sorry, go ahead.
Just, Charles, just to say, the triptans are widely regarded as the most effective agents out there for the acute treatment of migraine. In INTERCEPT, we had two-hour pain freedom rates that are amongst the highest, if not the highest, of recent oral entrants. You couple that with the results from MOMENTUM, where we showed statistically significant superiority over rizatriptan, widely regarded as one of the fastest acting, if not the most potent, of triptans. You put all that together, and now with INTERCEPT and MOMENTUM, the efficacy of AXS-07 has been described in a broad range of clinical settings. I think that it adds very compelling efficacy data regardless of timing of treatment or baseline illness severity or prior response, right? Because inadequate response was characteristic of the patients in MOMENTUM.
Now you have a broad breadth of efficacy data for AXS-07 in these varied clinical settings.
Yeah, very nice clinical efficacy. Last question. I think you enrolled 152 patients in the experimental arm, I think I saw that it was 140 patients that you were reporting data on. Can you just help us understand, did the 12 other patients just not have migraine?
No, actually, what happens there is either they didn't dose for whatever reason, they didn't have a migraine, or they withdrew consent. These numbers are what you'd expect to see.
Okay, good deal. Thanks for taking my questions. Congrats.
Thank you.
Ram Selvaraju with H.C. Wainwright, your line is open.
Hi. Thanks very much for taking my questions. Just three quick ones, if I may. With respect to how you expect to position AXS-07 relative to other drugs that are currently approved for migraine, can you give us a sense of specifically how the INTERCEPT data set is likely to aid in that positioning? Also, if you expect the INTERCEPT data, as strong as it appears to be, to have a significant impact on potential formulary positioning. Then secondly, I was wondering if you could comment on the safety profile, specifically in relation to another triptan formulation called Qtrypta, which apparently reported very low instances of triptan-like side effects in its pivotal program. Just wanted to see if you could provide some additional color on the incidence of specifically triptan-like side effects in your INTERCEPT study. Thank you.
Sure. Thanks, Ram, for the question. I'll turn it over to Dave to answer your positioning questions. With regards to the safety profile, we were very pleased with the safety profile. As you can see, we had to really look for very low cuts in terms of percentage of subjects reporting individual adverse events in order to come up with a table. So very low rates of adverse events, placebo-like in terms of triptan-like side effects. We have not seen anything that is out of the ordinary. Also, we are studying AXS-07 in our long-term open label safety extension trial, and those patients are actually dosing every migraine. So far, there's nothing unexpected that we're seeing. So we're very pleased with the safety profile. Dave?
Hey, good morning, Ram, thank you for the question. I think, when you think about the positioning of AXS-07, we are in a really good spot. Whenever we think about positioning, we think about what's the unmet need out there. Consistently, we hear that efficacy is what the greatest, by far, unmet need is in the marketplace. When you think about what we have to offer with AXS-07, we asked physicians at the end of last year, first based just on the MOMENTUM data, "Where would you position this?" What we heard was that for patients who had failed multiple therapies, they would prescribe this. 40%-50% felt like this is where they would prescribe it, AXS-07. They also said they would prescribe it for about 20% of their treatment-naive patients.
With MOMENTUM, we showed that for treatment-experienced patients, this is really a great therapy for you to choose because we're the ones who have data that shows superiority over standard of care in that patient type. You could first think of experience from treatment experience. What we've shown is in an all-comer patient setting, why wouldn't you move this up earlier? What we've shown now is if you take the therapy the way that physicians most frequently instruct their patients, three out of four patients are not going to progress beyond mild. We think from a positioning perspective, the positioning of AXS-07 will be really strong and superior efficacy over standard of care in an oral, convenient to take oral product with very favorable safety profile.
When you look at that, you would see us being used, certainly source of business up front would largely be the patients they're frustrated with and looking for a more effective option, but very clearly could move up to a first-line therapy. As far as formulary position, we're also in a very good situation. When you think of the type of data that payers are looking for, head-to-head superiority data, we think positions us very well for those discussions. In addition, now the data today say that if you take AXS-07 early, not only do you have the ability to not progress beyond mild, but you can return to normal functioning for three out of four patients. Really important to payers is the cost of rescue medications added to the therapy. What we saw today was only 15% use of rescue therapy.
That combined, that entire clinical profile, we think positions us very well with payers to be used early in the treatment of migraine.
Just with respect to the promotional sort of competitive environment, it seems to us anyway, that the bulk of the newly approved migraine agents are specifically targeting prevention. Their promotional message and overall targeting is going to be very different to that with AXS-07. Could you maybe comment on sort of the kind of promotional headspace bandwidth that you anticipate will be available for AXS-07 as and when it gets to the market? Thanks.
Well, first, I think with one of the greatest opportunities within migraine is just getting more patients treated and with a sense of urgency to improve the outcomes of these patients. Having more players in the market helps us draw attention to the unmet need, whether that's in the acute space or in the prevention space. Remember, every patient who's on a preventive therapy is also on an acute therapy. While there are strides to improve care for preventive therapies, when you look at one of the predictors of progressing from episodic to chronic migraine is insufficient effectiveness in the acute therapies. We have a very important role to play in terms of making sure that all of the patients who are on therapy, certainly on acute therapies, have the best, most effective option at their hands.
We think that we're in a very good position to be able to address that. The focus is on increasing efficacy in acute therapy, and anyone who has migraine should have an effective acute therapy in their hands.
Thank you very much.
Yatin Suneja with Guggenheim Partners, your line is open.
Good morning, everyone, and thank you for taking my questions and congrats on good results today. In terms of similar question or similar lines of question to what Ram asked earlier, just help us understand the label that you are hoping to get because INTERCEPT was more frontline, and then you have MOMENTUM, which was more lateline. That's the first question. The second part of the question I have is that it seems like you had excluded patients with cardiovascular disease. Can you maybe put some numbers around what proportions of patients or migraine patients have cardiovascular-related disease, and will you be seeking for a contraindication for that? Thank you.
Thanks, Yatin, for the question. With regards to the label, the indication that we'll be filing our NDA for is the acute treatment of migraine in adults with or without aura. That will be the label. With regards to the role of the MOMENTUM and the INTERCEPT trials, we think that both of these studies will be or are likely to be included in the product label. That should inform clinicians in terms of how to use the product. What's nice is with MOMENTUM and with INTERCEPT, we do have a broad range of patient types and disease severity and ways to treat the migraine. We do think that that will definitely be useful to have in the label. With regards to the exclusion criteria, that is a standard exclusion criteria.
In most clinical trials, you will exclude patients who have very severe underlying disease. Our exclusion criteria is pretty standard, and it's actually used in other migraine studies with other agents of other classes. With regards to what the implication of that might be for the label, we do expect that the contraindications that are in the label for triptans with regards to cardiovascular risk factors will be in the label for AXS-07. In multiple surveys, however, clinicians indicate that roughly it's in the teens, the percentage of patients who would be contraindicated or to whom they would not prescribe and are not prescribing
triptan-containing products. In our Mindset survey, it was somewhere between 12% and 15%. That's been replicated in other surveys of physicians.
Got it. Thank you very much.
Marc Goodman with SVB Leerink, your line is open. Marc Goodman, your line is open.
Sorry, I hear you. Can you give us a sense of what was the number of migraines that these patients had? I know that there was some inclusion criteria mentioned, but I was wondering, what was the actual number? Did you look at the patients to see if they had more migraines, did they respond better, and how that was? Were the patients on any background medication? Were they allowed to have any other triptans at all? Were they on prevention, just to make sure of that?
Thanks for the question, Marc. Cedric?
Hi, Mark. Yes, you're right. The inclusion criteria was on average two to eight migraines per month. We haven't yet looked at how it breaks down in terms of number of migraines. The other question were contraindications, or sorry, prohibited meds. They weren't allowed to be on other triptans, there weren't a significant. We would have to look at the numbers that were on prevention. I just don't have those numbers right in front of me now. It was very essentially an all-comers population with just the standard contraindications on prohibitions on comorbid conditions, cardiovascular disease, things like that, but otherwise, an all-comer population.
Some of these patients, or a lot of these patients could have been on CGRP prevention injectable?
I don't have those numbers right here with right now.
Yeah. If I may add to what Cedric just said, the way the study was designed is patients came in and prior to dosing with AXS-07, there was a one-month period of time where they recorded their migraines. In terms of the actual number of attacks that they had during that time period, we do have those data. We just need to analyze them. While, as Cedric mentioned, we don't yet have an exact percentage of patients who were receiving background preventative medications, including the CGRP receptor antagonists. Those were allowed. That was not an exclusion criteria. Patients could be on background preventative medications as long as those doses were stable and as long as they still met the criteria in terms of the number of migraines that they needed to have in order to be treated.
In terms of other medications, as you know, the way that these studies are designed, obviously, during the first two hours, since two hours is the primary endpoint, patients are not allowed to dose with any kind of rescue medication. Although some do dose just a little bit before, thereafter, patients are allowed to use rescue medications, which are the standard rescue medications, which might include triptans.
Then just second, in your market research, does it look like the product will be used after a triptan and possibly before CGRPs or equal to CGRPs? I'm talking about the oral rescues that were just approved. Just curious what your market research says?
Great. That sounds like a question for Dave.
Well, we did ask the question where physicians would use AXS-07, I think what really differentiates what we're offering is the superiority versus rizatriptan. That makes a significant difference in physicians' minds when they start to think through where are they going to place this product. When you think about typically what happens, they typically start with a triptan. More times than not, it does not bring the effective efficacy that they're looking for, they wonder, okay, what's the next best step? Our data that shows superiority over rizatriptan really helps them answer that question because we have the data that says for difficult to treat patients, AXS-07 is superior than rizatriptan in that next choice. I think the initial use for many physicians will be for those patients that they're struggling with.
Remember, our research also asked the question, would you use this in place or in front of emerging therapies, including oral CGRPs? Remember that 90% of physicians said that they would choose AXS-07 slightly, moderately, or significantly greater than CGRPs. It's because of that differentiated data. I think that's what is really exciting, is they're looking for head-to-head superiority data, and I think that puts us in a very good position relative to new entrants as well as traditional entrants. The final point I would make is that would be for those patients who have already been treatment experienced. Again, I would echo, physicians also said that they would prefer AXS-07 for just over 20% of their treatment-naive patients. They're looking at specific types of patients that they think need this type of efficacy right out of the bat from the very beginning.
We would expect that the MOMENTUM data, now coupled with what we see about the ability to prevent the progression of migraine pain could really move us up into first line for a percentage of those patients. Thank you.
Thanks.
Myles Minter with William Blair, your line is open.
Hi, guys. Good morning. Congrats on the data. Just the first one on the patient baseline demographics. I'm curious whether the breakdown of most bothersome symptoms at baseline in INTERCEPT were similar with MOMENTUM. I know Cedric made the comment on the INTERCEPT trial here that 23% had nausea. I don't think I've heard that commentary out of MOMENTUM. Considering their different patient demographics, I was just curious as to how those both match up. I have a follow-up after that. Thanks.
Good morning, Myles, thank you for the question. We have not done the full exact analysis, but we certainly have those numbers, and we would expect that they would be similar. We'll get those precise numbers to you, though.
Okay. Thanks for that. Then just back on the Mindset survey, just curious what the breakdown of survey participants were of primary care providers versus migraine specialists, like your Richard Lipton of the world. I'm just thinking that even though 20% might prescribe this in treatment-naive patients, whether or not that's going to be your initial sort of sales targeting process considering prior commentary that you'd probably target the specialist centers first and then build out to primary care physicians later.
Thanks, Myles. It's Dave. When we looked at the Mindset survey, we did ask physicians who were treaters of patients with migraines. The criteria to enter the survey was to treat at least 100 patients personally or actively in a 12-month period. The breakdown was around 40% of them were headache specialists, around 35% were neurologists, and about 24% were primary care physicians. When you look at the bulk of the prescribing, these are the type of physicians that we think represent the bulk of where, or a disproportionate share of where the patients reside. That's why we feel confident in asking these physicians what their distribution would be across treatment-naive all the way through treatment-experienced.
We still feel confident that a targeted approach to these types of physicians, those that have a high volume of migraine patients, makes sense right from the beginning. As we move into greater adoption and payer formularies start to kick into place, then we'll have the ability to scale quickly based on the trajectory of adoption. We think a targeted approach at the very beginning still makes sense, not only to capture the treatment-experienced, but treatment-naive patients, and then the ability to scale very quickly.
Okay. Just a final follow-up from me. Just your thoughts on maybe moving from an oral pill into an injectable format or an orally dissolving tablet, maybe even an intranasal formulation, given optionality is also an issue for patients out there as well. That's it from me. Thanks.
Those are definitely options, and I think certainly one of the things that we are exploring are alternate formulations for the pediatric population. Stay tuned, and we'll provide you more information on that later. Thank you.
Bert Hazlett with BTIG. Your line is open.
Yeah, thanks for taking the question and congratulations on the supportive results. I realize that the current regulatory standard is pain freedom and most bothersome symptom freedom at two hours. Did you happen to look at one of the older measures, pain relief at two hours in this study?
Hi, Bert. Thanks for the question. The way that this study was designed, the study was designed specifically to have patients treat their migraine pain at the earliest onset of migraine while the pain was mild. We looked at pain freedom, meaning then you completely eliminated the pain. In this case, since you're comparing it to baseline, pain relief and pain freedom are identical.
Okay. Thank you. The measures at one hour, given what you saw in MOMENTUM, were you kind of surprised you didn't see more of a separation at one hour?
Not at all. Again, the point of the study was to have patients treat their migraine pain at the earliest sign of migraine pain. The point was to actually prevent patients from progressing. We saw that, we demonstrated that very convincingly. Not only were we eliminating pain in a third of patients, but then we prevented pain from progressing from beyond mild. When you look at all that together, then almost three quarters or 75% of patients either had their pain totally eliminated or did not progress beyond mild. Now, having said that, we still did see numerical separation and numerical superiority starting at 30 minutes. Now, when you think about the results of this trial and think about the p-values with statistical significance that we showed, it's important to remember that we dosed a total of 283 patients, and we enrolled 302.
That's about 130 or so patients per arm. To have been able to show the high level of statistical significance that we showed really speaks to the effectiveness of the therapy.
Okay. Terrific. Just shifting gears briefly, and sorry to do this, but just wondering about the commitment to narcolepsy phase III and the second AXS-05 phase III. Are you still anticipating that? Again, things seem to be changing daily based on the effects of COVID. I just want to know whether there's been any additional consideration with those two pivotal studies.
Yeah, we are moving forward as planned with our CNS pipeline. It is very robust. With regards to narcolepsy, the plans have not changed at all with regards to launching our phase III program, and we're still on track to do that. Planning is still underway, and everything is moving forward and is on track with regards to narcolepsy. Similarly with AXS-05, with our other planned phase III trial, that is also moving forward. We gave guidance most recently that we expected that study to start in the Q3 . We're moving forward.
With regards to COVID in general, we are in a very advantaged position given that our efficacy trials, which are needed for commercialization or which are needed to provide the first evidence of efficacy, for example, our ADVANCE pivotal trial in Alzheimer's disease agitation, we're very advantaged that all those studies have completed enrollment. We are in a good position. The actual timing of the launch of additional trials, I think, does allow us certainly enough time to see how the impact of COVID hopefully wanes by the time that we plan to launch those studies.
Okay. Congratulations again on the data. Thanks for the additional color.
Thank you, Bert.
Matt Kaplan with Ladenburg Thalmann, your line is open.
Hey, guys. Good morning, and thanks for taking the question. Just wanted to dig in a little bit more to the differentiation of AXS-07 with respect, I guess, given the MOMENTUM results where you clearly showed superiority rizatriptan and now the INTERCEPT results. I guess maybe a question for Dave. Help us understand in terms of the reduction in the use of rescue meds and in terms of the durability of the pain freedom, how do you think this will play with payers and impact on, I guess, now MOMENTUM and INTERCEPT helping you to get on the different schedules with payers?
Sure. Thanks, Matt. I think when we look at what payers are interested in, the type of data that we've generated, I think, is really in line with fostering great discussions with payers. Look at what payers are dealing with kind of day in and day out. They're dealing with kind of a merry-go-round of triptans for many of these patients where they try one, try another, try another. Yet frustration with efficacy remains, disability remains, use of rescue medications remain. We have the ability to go in a very unique position to say, For many of those patients who've been on that merry-go-round of triptans, what's the next best use that you can look for an effective therapy that can change that future? Our superiority to rizatriptan really helps answer that question for many of those patients that are difficult to treat.
When you look at those data from MOMENTUM, you look at our ability not only to quickly deliver efficacy, but also then to sustain it. Of course, that leads to the reduction in rescue medication. That has a great benefit to patients, but it also has a nice economic benefit, too. When you think of the overall cost of managing migraine, which has been estimated certainly in the neighborhood of $78 billion in direct and indirect costs in the U.S., then we think a big driver of that is the lack of efficacy. We're in a very good position to come in in a very differentiated stance in terms of our clinical data, and then also have that available in a form that patients and clinicians prefer in an oral format, and with a tolerability profile in these trials that have been very favorable.
I look forward to the discussions with payers. I look forward to delivering the type of clinical profile that we think they're interested in that delivers patient benefit, clinician benefit, but also clear economic benefit as well.
Great. That's very helpful. Thanks for the color and congrats on the results, guys.
Thank you, Matt.
There are no further questions at this time. I would now like to turn the call back over to Herriot for closing remarks.
Thank you all again for joining us on the call today. We are very pleased with the additional data generated in the INTERCEPT trial for AXS-07, and these data confirm the superior and durable efficacy of AXS-07, and also it expands and enhances the differentiated profile of this product candidate in the acute treatment of migraine. We remain on track to file two NDAs by year-end, one for AXS-07 in migraine and one for AXS-05 in major depressive disorder. We look forward to reporting top-line results for our pivotal ADVANCE trial in Alzheimer's disease agitation in early Q2 . Thank you.
This concludes today's Axsome Therapeutics conference call. We thank you for your participation. You may now disconnect.