Good day, ladies and gentlemen, and welcome to the Milestone Pharmaceuticals RAPID Top Line Data Conference Call. As a reminder, this call is being recorded. I'd now like to turn the call over to Brendan Burns with Argot Partners. Please go ahead.
Thank you, operator. Good morning, and thank you for joining us today for a review of top-line results from the RAPID trial. As a reminder, a slide webcast accompanying today's remarks is available at Milestone's website at milestonepharma.com. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent annual report on Form 10-K, as well as other reports filed with the SEC. Any forward-looking statements represent Milestone's views as of today, October 17th, 2022, only.
Delivering prepared remarks on today's call will be Joseph Oliveto, President and Chief Executive Officer, Dr. David Bharucha, Chief Medical Officer, and Lorenz Mueller, Chief Commercial Officer. Following prepared remarks, we will open the call up for Q&A, and joining us will be Amit Hasija, Chief Financial Officer, Jeff Nelson, Chief Operating Officer, and Dr. Francis Platt, Chief Scientific Officer. I'll now turn the call over to Milestone's CEO, Joe Oliveto. Joe?
Thank you, Brendan, and thank you to everyone for joining today's call. For the agenda, we plan to review top-line results from RAPID, our pivotal phase III clinical trial of etripamil in patients with paroxysmal supraventricular tachycardia, or PSVT. We will then provide commentary on our initial read-through of the RAPID results for the commercial opportunity, and we'll conclude with a review of the next steps for the etripamil program before opening up the call for Q&A. Excuse me. With RAPID data in hand, today marks an important day, not only for Milestone, but for patients and the healthcare community charged with treating those affected with PSVT. We are thrilled with the positive outcome and look forward to reviewing the data in greater detail shortly.
I'd like to start with a brief overview of PSVT and the impact it has on patients in order to provide some important context regarding the unmet medical need we are trying to address. PSVT is a highly symptomatic condition characterized by unpredictable episodes of very rapid heart rate that impacts approximately 2 million patients in the U.S. alone. The condition is currently managed chronically, either by use of oral calcium channel blockers or beta blockers to help reduce the number of episodes patients experience, or by catheter ablation, which is often curative but has some risks that causes most patients to opt against having the procedure. Once a patient finds themselves in an episode, there are currently no approved therapies that patients can take themselves to terminate the episode.
As a result, patients are left with the option to seek resolution in the emergency department through IV drugs, most commonly IV adenosine, or electrical cardioversion, the dreaded paddles. Both interventions represent an unpleasant and costly experience for patients, and this is exactly the area where we think we can help. Etripamil is a short-acting calcium channel blocker nasal spray designed to be the first patient self-administered treatment for terminating episodes of SVT wherever or whenever they occur. Supported by our extensive physician and patient market research, we believe that the opportunity for patients to self-treat their episodes and potentially take control of their condition is very meaningful. Now, let me move on to the results from the RAPID study.
To start, the RAPID trial met its primary endpoint with patients who self-administered etripamil demonstrating a statistically significant and clinically meaningful improvement in time to SVT conversion over the first 30 minutes compared to placebo. Further, etripamil demonstrated a favorable safety and tolerability profile consistent with that observed in prior trials, and we believe supportive of patient self-administration without the need for healthcare provider oversight. These safety and tolerability findings are particularly important given the repeat dose regimen that was implemented in this study. Lastly, analyses of pooled data from the NODE-301 and RAPID studies show that the etripamil treatment group had a statistically significant reduction in the use of rescue medical interventions and a statistically significant reduction in visits to the emergency department when compared to the placebo treated group.
Before I turn the call over to David to review the data in greater detail, I'd like to say that we owe our deepest gratitude to all those who participated in the study, including the patients and their caregivers, as well as the many dedicated healthcare professionals. Of course, I'd also like to thank the entire Milestone team for their dedication and steadfast commitment to our mission to bring etripamil to as many appropriate patients as possible. With that, I'll turn the call over to David.
Thanks, Joe. Turning to slide 8, I'll summarize the development plan for etripamil in PSVT. As shown on the slide, the clinical development program has been designed to support an NDA filing in PSVT, while also building an extensive safety database and assessing the drug's potential application in additional episodic cardiovascular conditions. For our planned NDA filing for patients with PSVT, the efficacy portion will be comprised mainly of the completed NODE-301 study and the RAPID study, of course, the top-line results of which we'll review shortly. For the safety package, we'll have data from the NODE-302 and NODE-303 studies. These studies, first of all, have had an open-label design in which only etripamil is administered. Second, both of these studies have yielded and will yield additional real-world experience as they allow for the treatment of multiple separate episodes of tachycardia.
Finally, we are also assessing etripamil in patients with atrial fibrillation with a rapid ventricular response rate, and we'll have some remarks on our AFib plans later in the call. The slide in front of you now shows the RAPID study. The RAPID trial was a phase III double-blind placebo-controlled trial of self-administered etripamil for terminating SVT episodes in the at-home setting. This slide shows the trial details of RAPID that are most important to better understand the targeted population and the drug treatment regimen. Study procedures are illustrated as we move from left to right, and enrollment at each stage of the study is denoted in parentheses underneath each trial stage. Starting on the left of the key inclusion criteria, I'd note that all these patients had a well-demonstrated history of PSVT.
Next, in moving to the right on the slide, all patients were given 2 test doses of etripamil, 70 milligrams each and separated by 10 minutes while being monitored in a physician's office. Next, patients passing the test dose were randomized 1:1 fashion to an etripamil treatment regimen or to a placebo one and were sent home with 2 double-blinded nasal spray devices. Shown in the purple rectangle, when a patient experienced an at-home event of perceived PSVT, he or she applied a wireless ECG monitor to the skin of their chest wall in order to record their heart rhythm, performed a vagal maneuver, and if symptoms persisted, administered the double-blind study drug.
In order to maximize the potential treatment effect of etripamil and to target those patients whose symptoms persisted for 10 minutes after the first dose, a repeat dose of study drug could be self-administered for those patients with still persistent symptoms. Excuse me. All ECG data were transmitted to a central and independent adjudication committee who made all assessments that went into the main endpoints. I'll describe those findings in a moment, but briefly, the patient demographics are shown on slide 10. This slide summarizes baseline characteristics of the 184 patients who make up the efficacy population in the rapid trial. All characteristics were well-balanced between the placebo and etripamil arms. Now let's review the primary efficacy analysis from the trial. As stated in our press release from earlier this morning, the rapid study achieved its primary endpoint with a high degree of statistical significance and demonstrated clinical efficacy.
The slide in front of you shows a Kaplan-Meier plot revealing both the primary endpoint at 30 minutes and a demonstration of PSVT conversion over the 90 minutes following the first dose of etripamil or placebo. The x-axis shows the time for when patients first self-administered study drug. The y-axis shows the cumulative conversion rate from SVT to sinus rhythm. I first draw your attention to the vertical dotted line at 30 minutes. There's clear separation between the etripamil regimen-treated patients and those on placebo. Namely, there's a 64% conversion rate in the etripamil arm, and this is 33 absolute percentage points superior to the conversion rate under placebo. Note that at the top of the dotted line, the hazard ratio of 2.62 represents robust efficacy, and the P value of less than 0.001 demonstrates a high level of statistical significance.
The next observation is starting on the left of the curves. At the very beginning, the curves separate early and stay separated throughout the observation window shown on the slide, with the etripamil treatment arm clearly showing greater conversion rates compared with placebo. Moreover, throughout this observation window, at every time point except for one, there is separation with statistical significance. Data from these curves also show information regarding the median time to conversion from PSVT to normal sinus rhythm. Patients in the etripamil arm had a median time to conversion that was more than threefold quicker than patients on placebo. These data all taken together show that patients on this etripamil regimen described here have a much greater degree of conversion and have a much faster conversion and by a large margin, and the degree of superiority is significant. Moving to the next slide.
This presents one of our key secondary endpoints, mainly a reduction in medical interventions and emergency department visits in combined data from the RAPID study and the NODE-301 study. The RAPID study included a key secondary endpoint examining the need for patients to seek rescue treatment, rescue medical interventions, or the need to simply seek care in emergency departments. Here we present the combined analyses of RAPID and NODE-301 study that demonstrate together substantial reductions in each of these two important measures with the significant P values noted on this slide. We believe that this is a strong result that not only demonstrates the efficacy of etripamil, but also further reinforces the value of etripamil's self-administration in the at-home setting. These findings also underscore the potential for this treatment approach to potentially reduce healthcare utilization. This next slide shows a summary of the RAPID safety analysis.
Overall, as demonstrated, etripamil showed a favorable safety and tolerability profile that is consistent with our prior clinical data, continues to support the drug's use in the ambulatory or the at-home setting. There's a paucity of serious or severe adverse events, again, consistent with our findings in prior clinical data. Of note, the vast majority of treatment emergent adverse events seen in RAPID were rated as mild or moderate. No patients treated with etripamil experienced an adverse event rated as severe, and there were no serious adverse events under etripamil treatment in this study. Next slide. On the top half of this slide, we present the most frequent adverse events observed in the RAPID study. As can be seen very easily, the majority of adverse events that did occur were localized to the nasal administration site.
These events were typically transient in nature and were most commonly characterized as mild, and in our experience, tend to recede over repeat applications. In the bottom half of the slide, we present a summary of those adverse events that we particularly examined that might reflect a lowered blood pressure, might reflect AV block, or might reflect an arrhythmia other than PSVT. As can be seen in this section of the table, no adverse event among this array of potential events was observed in a meaningful way. In sum, the RAPID trial achieved its primary endpoint with high degrees of statistical significance and demonstrations of clinical efficacy. The data demonstrate favorable safety and tolerability consistent with findings from our prior trials. Patients who self-administered etripamil needed to seek rescue treatments, medical interventions, or emergency department care less than those taking placebo.
In order to elaborate on how these trial data strengthen our conviction in the potential of etripamil to the PSVT treatment paradigm, I'll turn the call over to Lorenz Mueller, Chief Commercial Officer.
Thank you, David, and thanks to everyone for joining us this morning. I'm very excited about the results from the RAPID study because I believe it delivers the profile we had hoped it would to ensure patients, physicians, and the broader healthcare system all derive great value from a potentially paradigm-changing treatment like etripamil. Let me tell you what I mean. Starting with patients, market research has consistently shown how much those who suffer from PSVT would value a drug that would empower them to self-manage their disease and not have to go to seek the care of their physician or rush to the emergency department. Etripamil in the RAPID study converted two-thirds of patients within 30 minutes and almost 75% within an hour, effectively allowing them to get back to their lives.
We believe that results like these will make patients want to seek this treatment and have a good experience with it, which in turn could drive persistency. For prescribers, safety has always been foundational to their attraction to the potentially paradigm-changing nature of etripamil. Bottom line, etripamil has to be safe for physicians to feel comfortable with their patients self-managing an episode of SVT at home, and the RAPID study clearly delivered on that goal. Market research has shown that with a strong safety profile, the bar is low for cardiologists to prescribe etripamil to the majority of their patients. Payers have also expressed interest in etripamil, partly because they recognize the clinical need within this patient population, but also because they are excited about the value of an almost 40% reduction in emergency department visits, as evidenced by the study results you just saw a few minutes ago.
Given the unpredictable nature of PSVT, of course, payers will likely want us to come to them with data to help them understand frequency of use, which we will be prepared to do based on data being collected in our open-label studies. Let me now briefly review the U.S. market opportunity for etripamil in PSVT that we believe can be realized by the RAPID study results. Currently, there are approximately 2 million diagnosed patients with PSVT in the U.S., which we estimate will grow to 2.6 million by our peak year of sales in 2030. A large observational study we completed in 2021 demonstrated that 40%-60% of these patients have episodes that are burdensome enough in terms of duration and severity of symptoms that they would want to seek treatment. This is our target addressable market population of approximately 1-1.6 million patients.
As mentioned earlier, quantitative market research with cardiologists has shown that efficacy and safety findings like those demonstrated in the RAPID study result in over 50% stated adoption, which yields peak patient shares of 500,000-800,000 patients. The observational study I just mentioned also showed that patients with PSVT experience a median of 12-15 episodes per year, of which they report 30%-40% are the most burdensome, which leads us to estimate an average patient will use etripamil about five times per year. Doing the math on these numbers defines a peak year volume of 2.5-4 million episodes treated. Using conservative pricing assumptions based on Medicare specialty tier thresholds, this defines a core net revenue opportunity for etripamil in the United States of $2-$3 billion. With that, I'll turn the call back over to Joe.
Thank you, Lorenz. Moving to our regulatory next steps. While RAPID represents our largest and most informative PSVT study ever completed and meets our original agreement with the FDA for a single study efficacy approval, this slide shows the results of RAPID in the context of the overall efficacy package. I'll point out an efficacy package with consistent results across studies and across regions. Moving next to the safety on the next slide. The RAPID study showed safety and tolerability data consistent with that seen from earlier studies. The program to date now has exceeded 1,600 patients from multiple regions, apologies, and in multiple settings, having been exposed to etripamil doses of 70 mg or greater.
We believe we have the package needed to approach the FDA with an NDA filing plan and are in the process of doing that immediately with the expectation to file the NDA in mid 2023. Moving to the next slide to summarize. The RAPID study achieved its primary endpoint with clinically meaningfulness and strong statistical rigor, reaffirmed a consistent safety and tolerability profile seen in prior studies, and in pooled analyses with NODE-301, etripamil resulted in reductions in emergency department utilizations when compared to placebo. Our initial commercial read-through is that RAPID analyses provide valuable data to support etripamil's potential to allow patients better control over their condition and value to the healthcare system through more cost-effective ways to overcome episodes. On the regulatory front, as just mentioned, our plan is to file the etripamil NDA for PSVT in mid 2023, pending FDA feedback.
With that, let's open the call for questions. Operator?
Thank you. We'll now begin the question and answer session. To ask a question, you may press star then one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. This time, we'll pause momentarily to assemble our roster. Our first question comes from Chris Howerton from Jefferies. Please go ahead.
Hi. Good morning. Just congratulations on the great results, and thanks for taking the questions. Maybe just two kind of detailed related ones and then one higher level one. For the detailed related ones, obviously a great result in terms of the relative reduction of the emergency department visits or the medical interventions. Could you give us the absolute numbers that were observed in the study? How many emergency room visits or interventions did you actually observe in this study? Second kind of more detailed question would be, obviously the safety looks really great. And just one thing I wanted to just drill in a little bit. For those patients that received two doses of etripamil, were there any kind of stacking effects on any tolerability or any of the things that you observed in the overall profile?
Then the third question may be for you, Joe, or whoever else. Obviously, you've stated that you feel you're ready to go and approach the FDA, but what is your feelings around regulatory approach in other territories? Then, of course, how are you going to support that commercially? Thanks so much.
Great. Thank you, Chris. Thanks for the accolades and the questions. I'll take the first and third, maybe turn it over to David for the repeat dose question. With regard to medical interventions, as some of the audience may remember, we had some worries. We had seen great trends in medical intervention reductions in NODE-301. We had some questions as to whether the people would utilize the emergency department to the extent they did pre-COVID in the COVID world, which I'll remind everyone, RAPID was run completely during the time of COVID. Good news is that they did avail themselves of the emergency department and medical interventions. I'd say in general, the size of the numbers are of similar size to NODE-301.
Chris, we're actually kind of holding back on specific numbers as we are really interested in trying to get this material in front of some medical conferences and trying to escape the thin line of embargoes. We're actually holding back on the specific numbers for that reason.
Sure.
Yeah. I'm going to let David handle the second one and then move on, and I'll come back on the EU story.
Hey, Chris, good morning. Thanks for your questions. In terms of the potential for repeat dosing, let me make several points. The first is, the majority of the patients in the study self-administered 2 doses. Second point is, not surprisingly, a greater proportion of placebo arm patients utilized a second dose. In terms of your question about safety, we saw no material difference in the rate of adverse events between those patients who took only 1 dose and those patients who elected to take a repeat dose.
Great. Maybe I'll come back to the EU. The third question, Chris, on the EU. I think we've been very fortunate for this program to have generalized agreement, I'd say, between EMA and FDA across the board. Like many programs, they're never exactly aligned. That's always very tough. I think it's tough in many areas of the world. It's very good alignment in general, but with regulators, often hard to have 100% alignment. One of the areas that there is a little bit of a discrepancy in the view of our program was on the utility of the NODE-301 ad hoc analysis for efficacy and what our program with RAPID and NODE-301 would look like coming back to the EMA. We basically agreed to come back to them after these results.
Now, I think with RAPID giving such pronounced results and a P value of less than .001, I think that closes that gap for us and gives us, I would say, increased confidence to be able to go into the EMA with a full package. I think that's the main point. On the second, kind of somewhat related point, regulatory path and our ability to interact with and attract a commercial partner for Europe, which we've been public with wanting to do, I think has gotten substantially stronger as a result both of the regulatory path now that will be made clearer, we expect, as well as the commercial read-through that Lorenz had talked about really being applied equally to the U.S. and to other markets. I think more on the BD front will be coming from us in terms of our activities in 2023.
Okay, fantastic. Well, congrats again, and thanks for the answers.
Thanks, Chris.
The next question comes from Ritu Baral from Cowen. Please go ahead.
Good morning, everyone. Thanks for taking the question, and congratulations on this data set. I wanted to drill down a little further on what you think was happening between minute 5 and minute 10. Is that just a function of small numbers, or are you seeing sort of a trend, I guess, in PK/PD that suggests really the label should say everybody should take a second dose at 10 minutes? I've got a couple follows.
Sure. Why don't I start a little bit, Ritu. I'll start with the second answer first. Everything in this data set leads us to believe that we should not force everyone to go directly to the repeat dose administration. We believe pretty strongly that this data supports the idea of empowering the patient to treat their condition, monitor their symptoms, and then be able to choose whether they want to use that second repeat dose. We've talked about that extensively over the weekend as we looked about at this data, and we think not only will the data show that, but psychologically for patients, that gives them the opportunity to intervene as they wish and take control over their condition, something we really want to support.
I answered that, but I really want to turn it to David for the first 5 minutes or so, the first 5 to 10-minute questions.
Good morning, Ritu. Let me answer your question in two parts. The first is a general observation on our program, and that is, we believe very strongly, and the data substantiate this, that etripamil self-administration can be guided by patient symptoms. That's indeed what we studied in the RAPID trial. Etripamil treatment regimen that we examined very successfully should indicate that or demonstrate that patients with a second dose available to them for them to choose based on persistent symptoms are very able to make the decision that ultimately results in the efficacy findings that are shown. Brendan, if you could go to slide 11. That's where the efficacy findings are best shown and is the other part of your question, Ritu. When you look at the curves on slide 11, they separate very early.
Moving from left to right, you can see there's an initial upsurge in both the placebo conversion rate and the etripamil conversion rate. They then parallel for about the first 10 minutes. At 10 minutes, the placebo curve, the teal-colored one in this slide, tends to plateau off, whereas there's a second upsurge in the etripamil-treated patients. It stands to reason that the second dose that was administered at 10 minutes contributed to and was materially responsible for this second upsurge. That's the way I would read the event curves that you were describing, Ritu.
Got it. Super helpful. Thank you. The incidence of AV block. Can you give us just a little more background, as though it's first-degree AV block? Did this patient have a history of AV block, and did it resolve? Was this something seen with the second dose?
Yeah. As a first comment, let me put the finding of first-degree AV block in context. It is asymptomatic. It is an EKG finding and a very minor EKG finding. We track it just out of a sense of being very thorough, but first-degree AV block and the fact that it was seen in only one patient does not concern us. The attention that's been paid over the course of the development program to higher degrees of AV block, for example, second-degree AV block or third-degree AV block, and we've had zero instances of that in the RAPID trial as shown here on this slide.
Got it. Last question. Can you review for us the gating factors to filing outside of meeting with the FDA, specifically any CMC left to do or any either preclinical or phase I potential data generation that you anticipate, to check off the boxes?
Yeah, no, absolutely. Ritu, we'll want to speak to them as well about CMC, but like now for clinical, we feel we have the full package and have had that package for some time now on the CMC side, as well as any of the tox side or preclinical side. We feel this was the gating issue, as always final efficacy and then final safety on the clinical side. We feel like we're good to go and have confidence for a mid-2023 filing.
Great. Thanks for taking all the questions.
Thank you, Ritu.
The next question comes from Ted Tenthoff from Piper Sandler. Please go ahead.
Hi, guys. Congratulations on the data. I know a lot of hard work went into this successful trial. I was particularly impressed by the safety profile of etripamil. Can you go into detail about the discontinuations that we're seeing? Also, how does this data strengthen your belief in the opportunity for etripamil in AFib? Thanks.
Great. Thank you, Ted. I'll ask David to talk about discontinuations in the trial, and then I'll bring it back and talk about the AFib program.
Morning, Ted. For the discontinuations in the trial, as you can see on one of the slides we presented, there were three instances in the etripamil arm of subjects discontinuing due to an adverse event. These adverse events were not material in our eyes. I'd be happy to describe them to you. Two were several ectopic beats or unsustained ventricular tachycardia that is not infrequently seen when an SVT stops for any reason. If you give a patient IV adenosine, even in our placebo arm patients, when we would see SVT stop spontaneously due to placebo, there would be non-sustained VT in a couple of instances. These findings of drug-related AEs leading to study discontinuation are not surprising and quite frankly, they're not concerning from a medical standpoint.
Ted, with regard to read-through on the AFib program, you're exactly right. The way we read this safety data from the RAPID trial is that there is, as David said, a paucity of really serious events here. If you recall, the reason we went into the AFib program in phase II, the reason we went into the emergency department, very difficult area to do studies, is because the AFib population is older, more polypharmacy on board, and just a more complicated condition. We thought it would be wise not to, if you will, risk the PSVT program by going into AFib in the at-home setting and instead going into the controlled setting of the emergency department. That has been difficult to do, especially during COVID, to get studies done when patients are trying to get out of the emergency department and get through it.
I think what we're seeing here is a real confidence in the ability to now take the AFib program out into the at-home setting. We've already got plans. Although not quite ready for prime time, we'll want to incorporate this RAPID result and some other data we're seeing in the program that's encouraging to come out with an at-home study, probably another phase II study in AFib, that we'll plan to start, I'd say late next year. Late 2023, maybe early 2024. More to come on AFib, but super excited given what we've seen in RAPID now, especially with the repeat dose, which could lend well for AFib as well as the safety. Thank you so much for the question.
The next question comes from Leland Gershell from Oppenheimer. Please go ahead.
Hey, thanks for taking my call. Congratulations on the great news. Just a few questions from me. During the RAPID trial, could you reveal how many patients in each arm ended up going to the ER? And did this include any who were successfully terminated with etripamil? Also, we saw an oversubscription in the trial with about 760 people compared to an expected number of 500. Was there any driving factor behind this? Thank you.
Thank you, Leland. I'll handle both of those. We saw similar levels of emergency department utilization in RAPID that we saw in the NODE-301 study. We're staying away from exact numbers at the moment, Leland, just because we're really interested in a latebreaker and a potential presentation at a medical conference that we're still waiting for results on. That was one of the key questions that the committee asked us about and asked us to hold back on. We're going to respect that for now, and after that data comes out at the conference, we'll be happy to talk about the actual use of emergency department utilization in the study. Needless to say, I will say that it's in general similar levels that we saw in NODE-301.
Great question to pick up on the fact that we did over-enroll 700 instead of we were thinking 500 originally to fill the top of the funnel to get to 180 events. That was a little bit a result of just the way the enrollment went in this trial. Again, I'll repeat, this trial was a little tough to get off the ground as it started right after COVID was in full force, and being able to get study sites up and running was difficult. As we did that through the middle of the trial, and then particularly at the end of the trial, enrollment picked up significantly and we had a bit more of an influx of patients towards the end of the trial, and we enrolled right up until the time that we got our 180th event.
A lot of that over enrollment came from excitement and as new sites came on and as they just enrolled more patients. We saw it as a benefit because, again, we get more repeat dose utilization in a test dose and yields some of the numbers that you saw in the overall safety data set. We hadn't planned it, but we're very fortunate that we achieved it and now allows us to go directly to FDA with the filing package.
Appreciate it. Thank you.
The next question comes from Patrick Trucchio from H.C. Wainwright. Please go ahead.
Good morning, team. This is Jason on for Patrick, and thank you for taking the questions and congrats on the positive reports today. I guess the first question that we had was what percentage of the patient population from the RAPID trial took the repeat dose of etripamil? And if there were any analysis in terms of analyzing patients with a single administration compared to repeat dose, is there a difference in the conversion between these two populations compared to placebo? And I have a follow-up question after that. Yep.
Sure. Let me start with the first question. You may notice that, Brendan, if you can bring up the Kaplan-Meier curve, it's actually in there in a bit of a-
It's a footnote on slide 11.
Slide 11. If you pull up slide 11, it's a footnote in slide 11 when we try to give the overall demographics. Jason, as you may remember, some of these patients in the RAPID trial were rolled over, if you will, from the NODE-301 trial. These are patients that had events after NODE-301 top line data was cut and shown, and they had events later, and they had events while they had that study drug. 29 patients, for example, had events with only the single dose study drug in front of them. We removed them from the analysis. For patients that only had repeat dose study drug in their hands available to them, we found that approximately two-thirds of etripamil patients actually took the second dose. I believe-
79%.
On the placebo group, 79% took the second dose. That's understandable with the idea that etripamil is seeing an effect rapidly. For about a third of the patients, they converted within, or they likely converted within 10 minutes or felt like they converted within 10 minutes and then did not feel the need for the repeat dose.
Okay, great.
It's actually footnoted on slide nine.
Jason, can you repeat?
Yeah.
Go ahead.
The second question is just looking at the comparison between single administration of etripamil versus repeat dosing of etripamil and seeing whether or not the conversion time between these two populations are different.
Right. Jason, two comments there. The trial was not designed to do that, and the FDA informed us that we did not need to design any trials to definitively answer that question. The FDA will look at this as a treatment regimen. They will probably look to describe that somewhat in the label, but for the purpose of the trial, we did not look at that. Given its top-line data, we feel comfortable in just promoting this as a repeat dose regimen and really not getting into that because of really the trial design not being designed to help us with that answer. We will dig into that a little later and probably be able to articulate it in a little better form, but for today, we're going to just hold with that.
Okay, great. That's helpful. Just last question. Previously in the second quarter earnings, you guys had reported that the NDA filing would be in the second half of 2023, but now it seems like the timeline has been pushed up to mid-2023. What has enabled Milestone to kind of accelerate the NDA submission timeline?
Yeah. Well, actually, I'll just correct you. We've never formally given an NDA filing timeline, and that was largely because when we decided to put the repeat dose regimen into RAPID. We always knew we had a rough idea of what we would need, but when we decided to put the repeat dose regimen into RAPID, we would need to see what that regimen yielded. Did it yield extra efficacy or not? And did it yield any tolerability issues? With it delivering extra efficacy without any tolerability issues, we feel confident that we have the package now. I would say for the first time, we are ever coming out with our filing timeline, and that is mid-2023.
Okay, great. Thank you very much. Congrats on the progress.
Thanks, Jason.
This concludes our question and answer session. I would like to turn the conference back over to Joe Oliveto for any closing remarks.
Thank you, operator. Thank you again to everyone for their attention today, to our great analysts for the questions, and I'll just wish everyone a great rest of the day.
Conference is now concluded. Thank you for attending today's presentation. You may now disconnect.