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 call is being recorded. I'd now like to turn the conference over to your host, Mr. Mark Jacobson, Senior Vice President of Operations at Axsome Therapeutics. Please go ahead.
Thank you, operator. Good morning, everyone, and thank you for joining us on today's conference call to discuss the positive top-line results from the GEMINI Phase III trial of AXS-05 in major depressive disorder. A press release announcing that AXS-05 achieved the primary endpoint 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, 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 GEMINI clinical trial. Following Cedric's presentation, we will open the line for Q&A. Following Q&A, Herriot will provide some concluding remarks. I shall now turn the call over to Herriot.
Thank you, Mark. Good morning, everyone, and thank you for joining us on the call today. We are extremely pleased to announce that AXS-05, Axsome's novel oral NMDA receptor antagonist with multimodal activity, met the primary endpoint and rapidly, durably, and substantially improved symptoms of depression in the GEMINI Phase 3 trial in major depressive disorder or MDD. These results confirm and extend the positive findings from our previously completed ASCEND trial of AXS-05 in MDD. As a reminder, AXS-05 has been granted FDA Breakthrough Therapy designation for the treatment of MDD. The positive results of the GEMINI trial are potentially transformative for many of the patients who are seeking a new effective treatment option and for Axsome, since these data, along with the ASCEND trial, are sufficient to support an NDA filing for AXS-05 for the treatment of MDD.
We look forward to filing this NDA next year with the goal of making this therapy available to patients as quickly as possible. The GEMINI study was a phase III randomized, double-blind, placebo-controlled U.S. trial in which 327 patients with a confirmed diagnosis of moderate to severe depression were treated with either AXS-05 or placebo for six weeks. On the primary endpoint of a change in MADRS at week six, AXS-05 resulted in a substantial and highly statistically significant improvement as compared to placebo with a P value of 0.002. The antidepressant effects of AXS-05 were rapid, demonstrating high statistical significance on the MADRS at week one, the earliest time point measured, with a P value of 0.007. These effects translated to important improvement in quality of life and reduction in functional impairment for the patients treated with AXS-05 that were also highly statistically significant.
We are encouraged by the high degree of internal consistency of the results. Specifically, AXS-05 met all pre-specified secondary endpoints at week six with statistical significance, and the vast majority of these endpoints with statistical significance at week one. AXS-05 was well-tolerated and was not associated with psychotomimetic effects. The GEMINI results are especially important in light of the seriousness and high prevalence of MDD. An estimated 17 million adults in the U.S. experience a major depressive episode each year. MDD is the leading cause of disability in adults during their most productive years. Up to 70% of patients with MDD fail to respond adequately to treatment with currently marketed antidepressants. Currently approved antidepressants for MDD can take up to six to eight weeks to provide clinically meaningful response and are thought to act primarily through monoaminergic mechanisms.
The late onset of antidepressant efficacy has been associated with poor long-term outcomes and increased risk of suicide. The potentially fatal consequences of depression highlight the importance of rapidly and effectively controlling depressive symptoms. There is therefore an urgent need for new treatments with novel mechanisms of action and faster onset of action that are orally administered. AXS-05 is potentially the first and only oral NMDA receptor antagonist, also known as a glutamate receptor modulator, a new mechanism of action for the treatment of MDD. AXS-05 is also a sigma-1 receptor agonist and an inhibitor of the reuptake of monoamines. These mechanisms of action may be synergistic, resulting in the observed clinical effects of AXS-05 in patients with MDD. If approved, AXS-05 would represent the first mechanistically novel oral pharmacotherapy for depression in over 30 years.
AXS-05 is covered by 41 issued U.S. and international patents, providing protection out to 2034. Axsome maintains worldwide rights. I would now like to turn the call over to Cedric, who will review the GEMINI top-line results in greater detail.
Thank you, Herriot. The GEMINI, or Glutamatergic and Monoaminergic Modulation in Depression study, was a phase III double-blind, randomized, placebo-controlled, multi-center, six-week trial conducted entirely in the U.S. A total of 327 subjects with a confirmed diagnosis of moderate and severe major depressive disorder were randomized in a one-to-one ratio to receive treatment with either AXS-05 or placebo twice daily for six weeks. The total dextromethorphan/bupropion daily dose of AXS-05 was 90 mg / 210 mg in two divided doses. The primary endpoint of the study was the change from baseline in the Montgomery-Åsberg Depression Rating Scale, or MADRS total score at week six. Secondary endpoints included clinical response, remission, physician and patient-reported global assessments, functional and quality-of-life measures. During the course of the study, extensive quality control measures were employed.
The key entry criteria included adult outpatients fulfilling DSM-5 criteria for current major depressive disorder without psychotic features, who had a MADRS total score of 25 or more and a CGI-S score of 4 or more. There were no meaningful differences between the two treatment groups in terms of demographics and baseline clinical characteristics. The mean MADRS total scores at baseline were comparable between groups, 33.6 for AXS-05 and 33.2 for placebo. These scores reflect clinically depressed subjects with moderate and severe illness. Study completion rates were high in this study at more than 75% for both treatment groups. Turning now to the efficacy results. AXS-05 met the pre-specified primary endpoint by demonstrating a highly statistically significant reduction in the average MADRS total score at six weeks as compared to placebo with a p-value of 0.002.
The treatment effect was evidenced by a 16.6-point improvement in the MADRS for AXS-05, compared to 11.9-point improvement for placebo, for a placebo-corrected difference of approximately five points. The antidepressant effect of AXS-05 was rapid, with a clinically meaningful and highly statistically significant reduction in the MADRS total score compared to placebo at week one, the earliest time point measured. Statistical significance was maintained at all time points thereafter, reflecting both the rapid and durable antidepressant effect of AXS-05. A statistically significantly greater proportion of patients achieved clinical response on the MADRS, defined as at least a 50% improvement with AXS-05 as compared to placebo at week one and at every time point thereafter.
At every time point, the proportion of AXS-05 patients achieving clinical response was nearly twice that of placebo, with more than half of AXS-05-treated patients demonstrating a clinical response at week 6 with a p-value of less than 0.001. Turning to the results for clinical remission. Remission refers to the near complete absence of clinically significant symptoms of depression and as such, represents an even higher threshold of clinical response. It is defined as a MADRS total score of 10 or less. Remembering that the mean MADRS total score for all patients was approximately 34 at baseline, getting to a MADRS score of 10 points or less would represent, on average, a 70% or greater reduction in depressive symptoms for the subjects in this study.
The proportion of AXS-05-treated patients achieving remission was more than twice that of placebo-treated patients at week two and at every time point thereafter, and these differences were highly statistically significant. At week six, 40% of AXS-05 patients achieved remission, compared to 17% of placebo patients with a p-value of less than 0.001. This slide highlights the rapid onset of action of AXS-05, as evidenced by early and highly statistically significant separation from placebo on numerous secondary endpoints. As can be seen, AXS-05 was statistically significantly superior to placebo on nearly every measure one week after the start of treatment, the earliest time point assessed. Furthermore, this rapid therapeutic effect was durable and was maintained out to six weeks, with statistically significant effects on all endpoints at this last time point.
Rapid and statistically significant improvements were seen for AXS-05 on the MADRS total score, MADRS response, clinical remission, MADRS-6 subscale, the patient-reported QIDS scale, the Clinical Global Impression of Improvement, the Clinical Global Impression-Severity, and the patient's Global Impression of Improvement scale. Importantly, these antidepressant effects translated into statistically significant improvements in both daily functioning, as measured by the Sheehan Disability Scale, and statistically significant improvements in quality of life, as measured by the Quality of Life, Enjoyment and Satisfaction Questionnaire, reflecting tangible real-world functional benefits with AXS-05. Overall, multiple secondary endpoints pertaining to efficacy, quality of life, and daily functioning in the GEMINI study statistically favored AXS-05 as compared to placebo at week one, and these rapid and robust improvements were maintained over the entire treatment period. Now turning to safety and tolerability. AXS-05 was safe and well-tolerated in this trial.
The most commonly reported adverse events in the AXS-05 arm were dizziness, nausea, headache, diarrhea, somnolence, and dry mouth. There was only one serious adverse event, which was not drug-related. The rates of discontinuation due to adverse events were low in both treatment groups, 6% for AXS-05 and 1% for placebo. Importantly, treatment with AXS-05 was not associated with psychotomimetic effects or dissociative side effects. In summary, in the GEMINI study, treatment with AXS-05 resulted in rapid, durable, substantial, and statistically significant improvements in depressive symptomatology across multiple efficacy endpoints with AXS-05 as compared to placebo in patients with MDD. Furthermore, these symptomatic benefits translated into statistically significant improvements on validated measures of daily functioning and quality of life. AXS-05 was safe and well-tolerated, with a safety profile consistent with prior trial experience. Overall completion rates were high in this study, and discontinuations due to adverse events were low.
These positive phase III GEMINI study results replicate the early and statistically significant efficacy results previously demonstrated versus the active comparator bupropion, a well-established antidepressant in the phase II ASCEND study. With today's results, AXS-05 has now demonstrated rapid, clinically meaningful, and statistically significant efficacy with a well-tolerated safety profile across two trials in major depressive disorder. We would like to thank all the patients who participated in this important clinical trial. We would also like to thank the qualified and conscientious clinical site staff who collaborated with us in the execution of this important clinical study. With that, I would like to hand the call back over to Ariel.
Thank you, Cedric. I would 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 *one on your telephone keypad. To withdraw your question, press the pound key. Marc Goodman with SVB Leerink, your line is open. Marc Goodman, your line is open. Yatin Suneja with Guggenheim Partners, your line is open.
Hey, guys. Congrats on the results. Maybe just a couple questions for me. Can you maybe put these in perspective in terms of the effect size, what the effect size are? We know the currently approved agents have shown somewhere around 0.3, 0.35. Can you just maybe put that perspective up? Can you just help us understand what you achieved? I have a couple follow-ups.
Thanks, Yatin, for the question. With regards to the effect sizes, we haven't calculated those exact numbers, although you can probably extrapolate them from the data that we presented. What we will say is that the placebo-corrected differences are very significant, much larger than what has been reported with currently marketed antidepressants. If you look at the results during the first week, the placebo-corrected difference there is along the lines of what you see with standard antidepressants out to six weeks.
The results that we showed at week six, at the end of treatment, were about five points. Clearly, significantly greater than the currently marketed antidepressant drugs.
Got it. With regard to the discontinuation rate, can you maybe help us understand what the reasons were for discontinuation? Like what were maybe the top three reasons, and when exactly did these discontinuation occur? Were they earlier in the study or like when on the treatment curve they occur?
Yeah. Thanks for the question. We're really happy that the discontinuation rates due to AEs were very low. It was only 6% in the AXS-05 arm. The most common reasons for discontinuation due to AEs were anxiety, insomnia, and nausea. These discontinuations occurred really early in the study, right after randomization.
Okay. Just final questions. Can you maybe talk about the durability of these effects after week six? Are we going to get that information at some point? Were you evaluating patients after six weeks? Just like a broader one, when you alter this NMDA biology, does that sort of give a little bit more of a, or leads to a permanent change in how a patient would react?
What we've seen thus far in the GEMINI trial and also in our previous experience with AXS-05 in MDD is that the results are durable. Not only have we observed a very rapid antidepressant response at week one, which is actually only four days after the start of BID dosing, but it's been shown to persist and actually increase over time out to week six. That's the last time point that we measured. We do have an open-label safety extension trial. The majority of patients are rolling over into the open-label safety extension trial, which is encouraging, and that will give us longer-term data. Right now, we don't have that data, but there's no reason that we would expect, given the experience thus far during the first six weeks, to expect that this would not be a continued treatment effect.
Great. Thank you for taking my question, and congrats on great results.
Marc Goodman with SVB Leerink, your line is open.
Hi, this is Roanna Ruiz on the line for Marc. Thanks for taking the question. Just two for you. I know you listed the top adverse events as dizziness, nausea, et cetera. I was wondering if you could put that in context to other antidepressants and how that compares. Is it better, is it worse, et cetera? Then, my second question is just, kind of thinking ahead, how is the safety database enrollment going in context of this trial reading out? Thanks.
Yeah, thanks for the question. Actually, the rates for Adverse Events are lower than you tend to see in other antidepressant trials. To put the dizziness in context, it's much lower. We've seen some rates of up to 30% in the literature with other antidepressants. Given that the overall discontinuation rates due to AEs are also low, it speaks to the ability for patients to stay in the study and receive treatment benefit. In terms of the ongoing safety extension study, that will allow us to capture more over a longer period of time how this drug is being tolerated. Those results will be forthcoming in the future.
Great. Thanks.
Joon Lee with SunTrust, your line is open.
Hi, thanks for taking my question, and congrats on the great data. Just looking at the results today, your drug arm in the GEMINI behaves very similarly to what the drug did in the ASCEND study where you saw about a 17-point reduction from baseline. Regarding the placebo in the GEMINI, you saw about 11.9-point reduction, which is just 2 points shy of what bupropion did in the ASCEND trial. Is that 2-point numerical superiority where you expect for bupropion? Is that something that you would still expect in the upcoming STRIDE- 1 study early next year? If so, does that increase your conviction on the positive outcomes for the TRD study, assuming that the bupropion is just 2 points better than the placebo and you see consistent effect in your AXS-05?
The second question is, has the Data Safety Monitoring Board reviewed the safety in the STRIDE-1 study at any point? Thank you.
Thank you for the questions. With regards to the expectations of a treatment benefit with bupropion, we would agree sort of it's about a two-point difference. That's what's been reported in the literature. Our data are consistent. One thing that we would point out in the GEMINI trial is there was a very high placebo response. As you mentioned, it was 11.9 points in terms of reduction on the MADRS. This would be expected given that we had announced the positive results with the ASCEND trial which clearly would've influenced expectation bias in subsequent studies. Having said that, AXS-05 performed really well and was able to overcome that. If you look at the AXS-05 arm, the way that it performed in GEMINI and ASCEND, it performed very similarly. We're encouraged by that.
As it relates to STRIDE, certainly now having demonstrated efficacy in two separate trials in MDD with, AXS-05, that was robust. It definitely speaks well of the mechanism of action of the drug and its potential to have an antidepressant effect. It's clearly relevant to STRIDE, but we would caution that of course, STRIDE is enrolling a different patient population. It is enrolling patients with Treatment-Resistant Depression, which by definition means that those patients are a lot harder to treat.
Your next question.
Sorry. Has the Data Safety Monitoring Board reviewed the safety of STRIDE-1 thus far at any point?
Yes. There was one interim analysis that was conducted in the STRIDE-1 trial. It was an interim analysis for futility. It did pass futility, interim analyses for futility. The primary reason is of course, to look at efficacy. However, the independent data monitoring committees always look at safety. Yes. They did look at safety on an unblinded basis. Obviously, the company is blinded and there were no observations from that interim analysis.
Thank you so much.
Sure.
Charles Duncan with Cantor Fitzgerald, your line is open.
Hey, good morning, Herriot and team. All I can say is wow. Congratulations on a very well-conducted study and the results this morning. I had a couple of questions. Thanks for taking our questions. First is relative to the patient characteristics for the enrolled sample. How do you think those patients read on the broad potential use of AXS-05 in MDD? Do you anticipate the results to have positive predictive value for effect sizes in a more heterogeneous patient population?
Thanks for the question, Charles. I'll let Cedric just speak to what these results might mean in the broader MDD population. I'll just start off by saying that this was MDD and Cedric will talk to the severity of these patients at baseline and what he thinks that that might mean for clinical practice.
Sure. Thanks, Charles. Yeah, these patients with a confirmed diagnosis of major depressive disorder had on average, a MADRS score baseline of 34. It's often regarded that a score above 32 and into the 30s above that would represent a severely depressed population. With a mean of 34, you're getting a very good representative sample of depressed patients in the moderate and severe range. These patients were clearly ill, and also they were coming in with scores on the measures of daily functional impairment on the Sheehan Disability Scale, and also on measures of quality of life and enjoyment of life on the what's called the Q-LES-Q validated measures of quality of life and satisfaction that suggested significant impairment from their depressive symptomatology.
We're confident that in the GEMINI trial and indeed the ASCEND trial before that, we have captured a truly representative sample of MDD patients who are significantly impacted by their illness. Of course, this is different from the ongoing treatment-resistant population in STRIDE. In terms of the broad applicability and potential for AXS-05 as a treatment we're very encouraged by the fact that not only have we demonstrated efficacy in two trials now, but also the tolerability and safety profile characterize a drug that has very low discontinuation rates, is very tolerable, and results in rapid substantial and durable antidepressant effects. When you put that all together, I definitely can see no reason why this treatment wouldn't be chosen as a first-line treatment for a broad MDD population should it get approved.
Yeah, for sure. Very impressive results. Let me ask you a couple of questions regarding the future and next steps. One is NDA timing and really the gating activities to that. Any additional clinical studies? How do you feel about the CMC section readiness and ability to manufacture AXS-05? Would you need to do anything else beyond the clinical trial supply that you have?
Thanks, Charles, for that additional question. In terms of the NDA filing, we're in a very fortunate position that we now have two positive studies. Based on our Breakthrough Therapy meeting with the FDA, this puts us on track to file an NDA, which we're targeting for the second half of next year. One of the gating factors, and I think, the key gating factor, is the safety database. We do need a safety database of 300 patients who've been treated for six months and 100 patients who've been treated for one year. As you know, we did launch an open-label safety extension trial to capture those patients with MDD and TRD back in July.
We're capturing those patients, and we will have the one-year anniversary, hopefully of the 100 patients in the second half of this year, putting us on track to file the NDA in that timeline. With regards to CMC, we're in excellent shape with regards to CMC. The study drug that was used in our, and that is being used in our pivotal trials are in fact being manufactured at commercial supplies.
Okay. That's very helpful. Last question regarding commercial strategy. I imagine these results really get you to think very intently on that. Probably a little half-baked at this point, but if you had to guess, would this be a drug that you would market in-house completely, or would you do so with a co-promote, or would you out-license it for use in MDD and other potential indications?
Thanks for the question, Charles. As we've stated, we do intend to market AXS-05 ourselves in the U.S. We would look to partner outside of the U.S., but we're fully committed to marketing the product in the U.S. We think that that can be done by a company of our size. To that point, as you know, we did start recently in the third quarter to build our commercial leadership. In fact, Dave Marek , our Chief Commercial Officer, is sitting with us in the room.
Thank you, Charles. That certainly would be our intent. What we are planning in terms of moving forward is to look to commercialize it from Axsome in the U.S. Of course, we always keep options open to see how we can do that most effectively to get AXS-05 to the right patients who would benefit. Right now, we see the ability to do that within Axsome today.
Okay, great. Thanks for the added color, taking my questions. Great way to start the week.
Ram Selvaraju with H.C. Wainwright, your line is open.
Thanks for taking my questions and really congrats on this data. It's very clean and I must say that the GEMINI name was quite apropos because this looks so close to the ASCEND data. Congratulations. Wanted to ask about the timeline to presentation or publication of the GEMINI data, and also if you could clarify the time elapsed between first-line treatment during a major depressive episode and treatment with study medication for that 23% of patients who were specifically noted in the press release.
With regards to our presentation, we do intend to present the data at upcoming scientific conferences this year. We just got the data very recently, and we're sharing it with you now. Once we have confirmation from these scientific conferences, we'll let you know exactly at which of these scientific conferences that are upcoming, and you can probably guess which ones we're going to submit the data to. We'll make that known. In terms of publication, same thing. We are also launching publication planning with regards to this study, especially in light of the fact that we're very close, relatively speaking, to an NDA filing. For your question on the patients who were being treated during a current major depressive episode prior to enrolling in the study. I think the 23% number that you mentioned was from our ASCEND trial.
Okay.
We're still tabulating the exact percentage of those patients who appeared in the GEMINI trial. In terms of the timing of when they were on those prior antidepressants, they were on the prior antidepressants during the current major depressive episode. They were clearly washed out of any antidepressants that they were on prior to being randomized into GEMINI.
Just wanted to clarify what that washout period was.
The washout period was long enough to assure that there was absolutely no drug on board. It was at least five half-lives of the drug or one week.
Okay, great. Can you comment on what other recent comparator-controlled data sets exist in MDD and what the comparators were that were utilized there? It's my impression, and I think the impression of KOLs, that bupropion is a very effective active comparator, and therefore you chose a very high hurdle here. Just wanted to see sort of what the lay of the land is.
Thanks for the question, Ram. In terms of putting the data in context, and as we mentioned earlier, these results in terms of the treatment effect or the treatment difference are demonstrably larger than what has been seen with currently marketed antidepressants. In the ASCEND trial, we did use bupropion as the active comparator, and that performed similarly to the way that bupropion has performed in other trials with also a nice benefit from baseline. AXS-05 was able to, again, show superiority to that active comparator here in GEMINI versus placebo.
Just very quickly to clarify, regardless of what the STRIDE-1 outcome is, you are clear with the ASCEND and GEMINI data sets to file an NDA for AXS-05 and MDD, correct?
That is correct.
Thank you very much. Congratulations once again.
Robert Hazlett with BTIG, your line is open.
Yes, congratulations on an extremely well-conducted study. Hard to replicate the studies from one to another. You certainly did that. Congratulations to Cedric and the crew. The TRD. My question is with regard to how timing of that study result will impact at all the filing in MDD. Assuming success in STRIDE-1, how do you think about how that will be handled with regard to an NDA application for '05?
The timing of an NDA for AXS-05 and MDD will not be affected. The gating factor is not STRIDE. The gating factor is the open-label safety expansion trial. We are targeting the second half of next year for that NDA filing. We are on track to report top-line results from the STRIDE-1 trial in the first quarter. Assuming success in STRIDE-1, then those data would be very easily incorporated into an NDA filing.
Okay. Just a couple of quick ones. There was one SAE in the AXS-05 one that was not deemed to be study drug related. Maybe you mentioned that. Could you just mention what that was? Could you remind us of the IP estate of AXS-05, and is it evolving? If so, what should we expect in terms of that evolution?
Great. Thanks, [Bert]. Cedric here. The one SAE was pancreatitis. It was not related to study drug. It didn't occur while the patient was on drug. In fact, the subject completed the study. With regards to the IP estate, we currently have 41 issued U.S. and international patents covering AXS-05. They go out to 2034. The patents in terms of patent families fall into a couple of categories. One is pharmacokinetic patents which cover the exact PK profile, which is achieved with AXS-05. Those are agnostic to any indication. We're pretty happy about those patents. We also have claims covering the specific doses that are used with AXS-05. Also some of the claims cover the formulation which is used. The patent portfolio is evolving with the availability of efficacy data from now three trials. Really, if you count 12 patients.
That allows us to now prosecute more indication-specific claims. Those would be a new family of patents, and so we're looking forward to continuing to prosecute those and to having some of those issued.
Okay. Just a quick follow-up. Given that you have a comparator data with previous trials, does that, again, provide a rapid opportunity for the EU, either in terms of your filing or licensing or other business-related opportunities there?
It definitely advantages us with regards to European filing. One of the differences in regulations, typically between the U.S. and-- well, the FDA and then the EMAs is that in Europe, as you alluded to, clinical trials using active comparators are sometimes required. We're in a good position that many of our trials, including the ASCEND trial, have used an active comparator.
Okay. Congratulations again. Look forward to the filing and to the publication of the data. Thank you.
Thank you.
Myles Minter with William Blair. Your line is open.
Hi, guys. My congratulations on the data as well. Seriously impressive. My first question is just related to the demographics of patients enrolled. Did you enroll any patients that were comorbid with agitation? Did you capture that data from an efficacy perspective? Would that be data that we could expect to be presented at a scientific congress, maybe in advance of your ongoing trial, your ADVANCE-1 trial in AD agitation?
Thanks for the question. Yes, anxiety is often comorbid with depression and as a symptom of depression. It's interesting to look at a whole range of symptoms that occur in depression. If the patient's primary diagnosis was an anxiety disorder, they would not have been included in this study because this was a study in patients with MDD diagnosis. You're absolutely right that there's an opportunity to look at a variety of comorbid symptoms, and anxiety is one that occurs frequently in depression. We'll look further into the data as we do additional analysis and look forward to presenting the data at future conference.
Okay. Thanks for that. Just on the side effect profile as well, the dizziness, was the prevalence of that increased in more older patients out of that population? I'm just thinking about in an elderly population, dextromethorphan's being sort of attuned to falls in that population. Not saying that you had that here, but interested to see whether there was an age-related prevalence in those.
Well, the population in the MDD study were adults of the age of 65, so not an elderly population here. Also, the rates of dizziness were low comparative to other antidepressant trials, and discontinuations were also low.
Nothing on this.
Yeah.
Yeah. Thus far, first of all, the rates were relatively low, and there's no correlation with age.
Yeah, no signal for falling in the trial either.
Cool. That's helpful. Just assuming that STRIDE-1 is positive next year, correct me if I'm wrong, but it's an understanding that to get the TRD indication in a potential sNDA, you would need to run another well-controlled trial enrolling treatment-resistant patients. Could you potentially file with the STRIDE-1 data and incorporate that data set, assuming it's positive, into the MDD label so docs would have access to that when potentially prescribing this product? Thanks. That's it.
Yes. Assuming that STRIDE-1 is positive, then our expectation would be that it would be included in the package insert and the product label for AXS-05. Even though the overall indication would be MDD, the experience in patients with TRD and the TRD trial would be included in the clinical study section of the package insert. With regards to getting a formal indication for TRD, our working assumption is that we would need one additional study in TRD.
Okay, great. Thanks for the clarification. Cheers, guys. Congrats on the data.
Matt Kaplan with Ladenburg Thalmann. Your line is open.
Hi, good morning, guys. Congrats on the very impressive data in this study. I wanted to dig in a little bit more in terms of the onset of action, in terms of the rapid onset of action that you're seeing in this. Specifically, how that compares with other drugs in MDD. How to think about that with respect to any read-through to STRIDE-1 as well based on, I guess, this differentiating mechanism of action and the rapid onset of action that you're seeing in the GEMINI study.
Thanks, Matt. We were very encouraged by the fact that at the first week, we had a 2.4 difference from placebo. These are the kind of magnitudes of changes from placebo that often at 6 weeks for antidepressant trials result in statistical significance. We're seeing it at week 1. The rapid onset that we saw in GEMINI replicated what we saw in ASCEND, which is really encouraging against an active comparator. That maybe puts in context a little bit how other currently available antidepressants would look with regard to that. Of course then there's the important clinical parameters with getting to remission. Looking at response and remission and seeing those early achievements of really high thresholds for what's viewed as clinically meaningful.
I think that we stack up superior to what's available when one has to acknowledge that existing medications based on monoaminergic pathways often have to be taken for six to eight weeks before being able to truly assess whether a clinical benefit has been attained by patients. We're very encouraged by what we're seeing in terms of early onset.
Great. Thank you. One question in terms of the dose adjustment that you made in terms of initial dosing at QD dosing for the first few days and then to BID. Is that something you're replicating in the STRIDE-1 study as well?
Yes. We are replicating that in the STRIDE-1 trial and actually in all of our studies, essentially that's how AXS-05 is dosed. Once daily for the first three days and then starting at day four, getting the full dose, so BID dosing.
Great, thanks. Last question in terms of, can you update us on the status of the AD agitation study? When we should potentially expect a readout on those results?
With regards to the AD agitation study, that study continues to enroll well. I believe at the last update that we gave, the study was approximately 70% enrolled. That puts us on track for a readout in the first half of 2020. Towards the end of the first half of 2020.
Well, congrats again on the results and thanks for taking the questions.
Great. Thank you.
There are no further questions at this time. I would now like to turn the call back over to Axsome for final remarks.
Well, thank you for joining us on the call again today. We're very pleased with the GEMINI data readout, given its potential implications for the care of patients with MDD, which is a devastating disease. We look forward to an NDA filing for AXS-05 in this indication in the second half of 2020. AXS-05 is currently also being studied in a comprehensive program of CNS trials, including our STRIDE- 1 trial in TRD. We still expect that readout in the first quarter. Also in our ADVANCE- 1 trial in AD agitation, with a readout expected in the first half of 2020. Earlier this month, we did announce positive Phase II results of our AXS-12 product candidate for the treatment of narcolepsy. We anticipate launching Phase III trials with AXS-12 next year. We are also excited about AXS-07, our product candidate for the acute treatment of migraine.
The Phase III MOMENTUM trial of AXS-07 in migraine is on track for readout of top-line results by year-end. I'd like to thank the Axsome team for their hard work and dedication, especially during the month of December. Their hard work is allowing us to advance our CNS pipeline with the goal of providing new treatments for the millions of patients who are failed by current therapies. Thank you again, and we look forward to speaking with you again before the end of the year.
This concludes the Axsome Therapeutics conference call. We thank you for your participation. You may now disconnect.