Good afternoon, everyone. This is Andrew Weiss, Head of Investor Relations and Corporate Communications here at Idorsia. I welcome you to today's call to discuss the second set of phase III results for daridorexant in insomnia. In the call with me today are our CEO, Jean-Paul Clozel, and our Global Head of Clinical Development, Guy Braunstein. Both are here to walk you through our presentation and prepared remarks, which will then be followed up with a Q&A session. In that session, Martine Clozel will be able to also take questions. Next slide, please. I do need to remind everybody that we will be making forward-looking statements. You have been properly warned about the risks and opportunities of being invested in Idorsia. Next slide, please. I have the pleasure to hand over the call now to Guy. Please take over.
Thank you, Andrew. Good morning. Good afternoon, everybody. This is a presentation of the second pivotal study of daridorexant, and it's a follow-up discussion. I want to remind you that the first study results were shown in April, two months ago, a bit more than two months ago. I want to refer you also to the presentation that we delivered at that time. Of course, as we now have the two studies, it will be interesting to look at the data side by side, which will be done in the course of this presentation, which is leading me to the main conclusion that we draw from the second study, that we now have two positive single trials of daridorexant insomnia, and also the remarkable consistency of the results between the two studies. Next slide, please. We must be now on slide four.
This is a summary slide of the overall program that we have. We completed a while back a phase II program with two phase II studies, one in adults and one in elderly subjects. That was important because we could define the dose level that we wanted to study in the phase III program. It was also interesting to note from this phase II program that the same dose could be administered to adult and elderly patients. As a consequence, we could set up two pivotal studies looking at three different dose levels. The first study, called 301, that we reported in April, looked at the dose of 25 milligrams and 50 milligrams. The second study that we are going to describe today looked at the dose of 10 and 25 milligrams of daridorexant. In both studies, we included adults and elderly subjects.
The studies had a three-month duration and included patients with moderate and severe insomnia. The efficacy parameters, safety parameters were identical between the two studies. We had objective and subjective sleep parameters collected by polysomnography. I described them in detail in the previous presentation, and I would like again to refer you to that presentation for details, and we can discuss that in the Q&A if you need. I also want to mention that we had a range of subjective endpoints assessing the night using what we call the SDQ, the sleep diary questionnaire, which allows the patient to report on their feeling about their night, and in particular, the total sleep time that they perceive they have slept.
We also had, and that's unique to this program, an assessment by the patient themself of the daytime functioning using an instrument that is called the IDSIQ, Insomnia Daytime Symptom and Impact Questionnaire. This is a questionnaire that we developed at Idorsia and validated according to the FDA guidance. Again, I will refer you to the previous presentation for details, and we can discuss this instrument during the Q&A. As mentioned, we have now replication of the two complementary studies. The safety assessment included, of course, adverse events and a number of other parameters like vital signs, biochemistry, and hematology. More important and more specific to insomnia products, we also collected using a specific tool that I will come back on later on, the next morning residual effect.
We also collected the withdrawal and physical dependence and rebound of insomnia after withdrawal of the drug during a one-week observation. In addition to this program, of course, we have a clinical pharmacology program, which is not totally completed, and we will report later on on this program in a separate call. The next slide five, is showing the design of the trial, which you may remember is identical to the phase III 301 study that we reported earlier on. Just to remind you, there was a screening period of up to a month. The second part of the screening period was actually a single blind placebo running phase. During that placebo running phase, we collected subjective assessment using the sleep diary questionnaire, assessment of sleep, as well as polysomnography, which is represented at Visit three by the two bubbles.
We collected the polysomnographic criteria over two consecutive nights, allowing a clear assessment of the baseline. Following this placebo running phase, the patients were randomized at Visit four into three groups, placebo, 10 milligrams, and 25 milligrams of daridorexant. This was given to patients for three months, and we had, at one month and at three months, assessment of polysomnography again through two consecutive nights. During this whole treatment period, we continued to collect daily assessment of sleep as well as the daytime functioning using the IDSIQ questionnaire that I mentioned before. After the three months, when the patient had completed three months, they enter then into a single blind placebo run-out phase of one week, during which we continue to collect daily assessments of sleep as well as the daytime functioning.
We also included one placebo night to look at withdrawal symptoms and rebounds during this period. Finally, at the end of this single blind placebo period, the patient entered into an extension study if they wanted. The next slide is showing the study objectives. The primary objective was to evaluate the efficacy of 25 and 10 milligrams of daridorexant on objective sleep parameter collected by the polysomnography in patients with moderate and severe insomnia. The secondary objective was to evaluate the efficacy of 25 and 10 milligrams daridorexant on subjective sleep parameters collected with the IDSIQ, the sleep diary questionnaire, as well as the daytime functioning collected with the IDSIQ questionnaire in patients with moderate and severe insomnia.
The third objective, the safety objective, was, of course, very important to assess safety and tolerability of daridorexant, not only during the treatment phase but also upon treatment discontinuation to look at rebounds and withdrawal. On the next slide seven, we have now the description of the primary and secondary endpoints and how they were analyzed. Two primary endpoints were defined. These were nighttime primary endpoints, looking at the awakening after sleep onset by polysomnography. We call that WASO. Also the latency to persistent sleep, LPS, also collected by polysomnography. We had two secondary endpoints, one dealing with the night aspect, which is the subjective total sleep time recorded with the sleep diary questionnaire. We had the sleepiness score of the IDSIQ questionnaire, which is assessing how patient function during the day.
These subjective endpoints, subjective total sleep time, and the sleepiness score, were recorded every day on average over the treatment period on every week. The endpoint was the last week just preceding the polysomnography nights. We analyzed these endpoints according to the 10 milligram versus placebo dose, as well as the 25 milligram versus placebo, and we analyzed these endpoints at month one and month three. If you make the calculation, you will realize that here we have 16 comparisons versus placebo. Of course, we wanted to have a study-wide type 1 error control at 0.05. This is important in the context of making labeling claims. There have been a lot of questions when I presented that slide two months ago, a similar slide for the 301 study.
There have been a lot of questions about the structure of these 16 comparisons. So far, we were quiet about it. It's probably time now to disclose and discuss more fully how this was organized. This is shown on the next slide eight, which depicts graphically how we organized the 16 comparisons. I will try to explain that in as simple terms as I can. You see here the 16 H hypothesis comparison, H 1, 2, 3, 4, 5, 6, 7, 8 on the left, and then 9, 10, 11, 12, 13, 14, 15, and 16. The H 1 and H 2 were WASO comparisons and LPS comparisons, respectively. The green diagram shows the high dose versus placebo. For that particular study, this was 25 milligrams versus placebo at month one.
The blue following the green shows the high dose comparison, 25 milligram versus placebo at month three. Moving on to the right side of the slide, we have this pink showing the low dose, 10 milligram versus placebo at month one, and the purple part which shows the low dose, 10 milligram versus placebo at month three. Essentially, what we did was to prioritize 25 milligrams above 10 milligrams, and then within a certain dose level, to prioritize month one to month three. Therefore, the order of comparison was high dose month one, followed by high dose month three, followed by low dose month one, followed by low dose month three.
Within each of these buckets, high dose month 1 or high dose month 3, low dose month 1, low dose month 3, then we organize the comparison of the primary and secondary endpoint in a certain way. We started with WASO and LPS. Followed by H3, sTST, the subjective total sleep time, followed by the , H4. Similarly, H5, 6, 7, and 8 for the high-dose placebo at month 3. Then again, H9, 10, 11, 12 for the low dose of placebo at month 1. H13, 14, 15, and 16 for the low dose of placebo at month 3. What I would like to point out as well is that we started with the alpha value, type 1 error of 0.05. We carry on this alpha level according to how the statistical response is to the hypothesis.
Initially, we divided alpha into two in identical way to WASO and LPS. Therefore, the H1 and H2 are tested statistically at 50% of the alpha. Starting with 0.05, we divide into two, so H1 and H2 are tested at 0.025. If we can reject the hypothesis 1, then we can carry on the alpha level to the next level down. To do that, we divided the alpha level that is remaining. For example, if you win on H1, we can carry on 0.025. We don't lose any alpha, and we carry on to H5 and H3 similarly. Therefore, we divide the alpha of 0.025 into two identical levels, 0.0125 that goes to H3, and similarly, the same amount goes to H5.
If we also win on H2, we proceed in the same way, carry on half of the alpha remaining, which is 0.025, half of it going to H3, and half of it going to H6. By doing that, if we win on LPS and WASO, the alpha is received from WASO and LPS, and therefore receiving half of each, we again have the full alpha at that level. In contrast, assuming that we fail on H2, we don't reject H2, LPS as an example, then we lose the alpha that goes together with this comparison. The alpha of 0.025, which was associated with H2, is lost. However, as you see from the network of arrows, we can still continue to do the analysis.
The H3 can still be tested because half of the alpha from H1 is retained, then H3 can be tested at half of the alpha that was given to H1. If we win on H3 this time, we can also continue to H4, but interestingly, we can also continue to H6. Even if we lose, for example, on H2 LPS at month one, we can still go to H6 and test the LPS at three months. This is the methodology we have used to test the 16 hypothesis. This has been fully discussed with the FDA and agreed by the FDA. The last remark I would like to provide, which is important for this call as well, is that we don't need to win on more than one of the two, H1 and H2, to claim significance because they are tested independently.
We are not in a situation of co-primary endpoint, where you have to win on both of them to claim positive study. By dividing the alpha from the very beginning, we can claim positive if H1 is rejected or if H2 is rejected. This is important in the context of the current discussion, this is what allows me also to claim that the 302 study that we discussed today is a positive trial. I hope that was clear. It's a bit technical and complicated, because I've received questions on many occasions about this control of type 1 error across the 16 comparisons, I wanted to give you a bit more clarity on how it was done. The next slide nine, is now showing very classically the study patient disposition.
As you see that we had to screen a large number of patients, more than 3,600, nearly 3,700, to get 924 randomize. 25% of the patients were randomized. 75% didn't pass the criteria that we set forth in terms of randomization. This was primarily due to the fact that the patient recorded not sufficient insomnia on the subjective diary questionnaire and also for the polysomnography criteria. We wanted to be sure that we had very clear criteria for moderate and severe insomnia, and therefore, a number of patients had milder disease and therefore couldn't be randomized. Now continuing from the randomization, what we see, which is really very nice, is that we have a very high completion rate, 93%. Very few patients dropped out. Then the follow-up was the placebo run-out.
We have nearly complete data on the withdrawal during the run-out, withdrawal of treatment. Nearly half of the patients that were randomized actually could continue into the blinded extension. The blinded extension, which we call the 303 study, is still ongoing, and I'm not in a position to report the data from that study now. This will be the purpose of follow-up conversations. I'm sure you would like to see the results of the study, and that will be shown on the next slide 10. First, I would like to describe how the slide is constructed. On the left, you see the results of the first pivotal study, similar to what we presented at the previous teleconference. On the right, you see the results of the new study.
On the left, you see the results in green of the 25 milligram as placebo, and as a reminder, we see that there was significant improvement on both LPS and WASO at month one, as well as LPS and WASO at month three. You remember as well that the 25 milligram versus placebo was significantly improved for LPS and WASO. The study was positive on these two endpoints, as well as at three months for LPS and WASO. This is known, and you have seen that before. The new study provides very similar results. The 25 milligram of placebo shows numerical improvement of LPS, which was of borderline significance. The same at one month and three months. For WASO, it was highly significant at one month and three months. Interestingly, the 10 milligram of placebo showed numerical improvement on all these parameters, actually not reaching statistical significance.
When we look at the numbers, which I'm not allowed to give you because we would like to preserve the scientific integrity of publications, but I can tell you that the 25 milligram was numerically always superior to the 10 milligrams. We see an effect at one month. It was sustained at three months, and there is high level of consistency. You may question why we don't have numerical improvement, but no statistical improvement of LPS. I can't give you, again, the numbers, but I can tell you that numerically, they are actually very close to the 25-milligram data that we had in the first study. The next slide 11, is showing the results for the subjective TST.
As we see here, on the left, we had the positive data for 50 mg versus placebo at month one and month three for subjective total sleep time, and similarly for 25 mg of placebo. In the new study, the 302 study, we see on 25 mg versus placebo, significant improvement at one month and at three months on sTST. Again, for the 10 mg versus placebo, there was numerical improvement of a lower magnitude compared 25, and it didn't reach statistical significance. At this point, I would like to remind you what I said about the structure of the alpha spending function, so that you understand that even if we don't reject the hypothesis for LPS, we could still test the subjective total sleep time, although it was a secondary endpoint. Again, the effect that we observed at one month was sustained at three months.
The next slide 11, will show the results of the daytime functioning using the ESS questionnaire and the sleepiness domain.
Guy, you're on slide 12. You said 11. Sorry.
Slide 12. Thank you, Andrew, to remind me that. On slide 12, we see the ESS sleepiness domain. This is an assessment of the patient daytime functioning. The results were significant for the 50 milligram of placebo at one month and three months, and numerically better than placebo at one month and three months for 25 milligrams. We have very similar results in the second study with numerical improvement versus placebo in 25 milligrams, actually larger than on 10 milligram and not reaching statistical significance. Again, we see the consistency of the studies and the effect that we had sustained from one month to three months. This is in a nutshell, the results of the efficacy data that we collected during these two studies. I will now move to the safety data, slide 13. This is an overview of the treatment emergent adverse events.
We see that there was no huge difference between the. Again, showing the first study on the left and the second study on the right. We see that on the number of adverse events, we don't see much of a difference between placebo and the active doses of daridorexant. We see no tendency to dose response between the different doses. We see very few patients that had adverse events leading to premature discontinuation. We see very few, a handful number of serious adverse events, and also a very small number of adverse events of special interest, which were adverse events adjudicated blindly by an independent adjudication committee. Slide 14, the next slide, is showing a bit more details on the type of adverse events. We see a high level of similarity between the two studies, the main adverse event being nasopharyngitis, which I believe is really innocent.
We see a few patients with headache. We see very little number of patients with fatigue, dizziness, somnolence. You see the data here. Accidental overdose and nausea. No surprise of these numbers, and they are very much aligned to what we observed in the 301 study, with again, no tendency to an increased number of events from 10 milligrams to 25, and then to 50 milligrams. On the next one, slide 15, we give you a bit more data maybe that you haven't seen so far. Events adjudicated by the safety committee, and you see the numbers here. It's very difficult to debate about these numbers because they are very small.
For some narcolepsy-like symptoms related to complex sleep behavior, including hallucinations, sleep paralysis, you see a very small number, but I cannot give you the breakdown by treatment group because this would have the potential to unblind the 303 study, because these patients are actually continuing in the 303 study. Therefore, knowing on which treatment group they are would potentially unblind the study, and the 303 extension is blinded. On the bottom, you see again, the repetition of the somnolence, same number as before, and the number of adverse events, which are very relevant to an insomnia product, in particular, the number of falls that we had. You remember the small number in the 301 study. We have also a very small number in 303. Also depressed mood, again, very small number of patients. Overall, we are very pleased with the safety results.
I can now move on to slide 16, which is my concluding slide, using the same format as we have used in the previous presentation. The tick box indicates that we could reject the hypothesis and demonstrate efficacy on WASO on LPS at 50 and 25 milligrams in the first study, and for WASO on the second study, being close to significance for LPS in the second study, and nothing significant for the 10 milligrams, which is actually something we find very interesting. From a safety perspective, we didn't see a dose-dependent treatment-emergent adverse event. We see very low rates of clinically relevant adverse events. I can add that we didn't see morning hangover effect. This was assessed using a visual analog scale every morning as part of the IDSIQ questionnaire, assessing whether the patient would feel some somnolence resulting from the drug that was given the previous night.
We see rather a tendency to an improvement versus baseline and an improvement on active as placebo. We didn't see any sign of rebound, and we didn't see any sign of withdrawal symptoms during the placebo run-out period. Having said that, this completes my presentation. I will hand over to Jean-Paul.
Thank you, Guy, again, congratulations for this program. Maybe I can go to the next slide. Just to say, Idorsia took a lot of risk in designing this program because, in contrast to what is done usually, we tested three doses in phase III. We really wanted to have a statistical analysis including 16 comparisons, four main primary endpoints with two time points, one month and three months. Also, we had planned a design where the middle dose, 25 milligrams, would be common to the two studies, and the data would be in a later time could be pooled. I think that this program really shows a fantastic result because the two studies are very consistent, as was mentioned by Guy. Now with this data, I think really we have a very good idea of the dose response.
Usually, in phase III, you never get such precision, not only on the dose response for efficacy, but also for safety. We have seen that 10 milligrams has nearly no effect, but 50 milligrams has outstanding effect without safety penalties. This information, I think, is key for the authority, for the regulatory authorities. This is the reason why now we are really working, and the whole company is working very hard to submit an NDA before the end or around the end of this year. We are going to meet the FDA this autumn to prepare for this timing. That's the very important point. Now we have to prepare for the launch. What next slide. We are on slide 18. What is going to be important for a successful launch? First of all, of course, we have very clear data.
When you will see the data, you will understand how, I would say, striking how two studies can give data so close. More important, I would say, than even the data is the drug. Because we have a very unique drug. Again, I would like to say it's not by chance that we have seen this outstanding effect. The project started 22 years ago, and it took us, this is the third drug that we put in clinic. We wanted to have absolutely a drug with a very fast onset of action, peak effect around the peak dose in the pharmacokinetic of one hour, and we wanted a short half-life around five to six hours to allow for getting an effect on sleep onset, while without having this morning hangover effect. Of course, there is still this finding about the data. These are outstanding findings.
We still do not know what is the mechanism of this improvement of daytime functioning. Of course, it's going to be very interesting to go through the data and to try to understand better these findings, which is really striking. As we said, this NDA will be filed before the end of the year. Now the company has to get prepared for the commercial launch. You will hear more during this year, but we are working very hard in terms of branding, but also in terms of preparing, especially the United States affiliates, in order to be able to launch in the best conditions daridorexant. Next slide. It's slide 19. I think that what is important is that this program has to be put into the context of our visions in Idorsia.
It shows our ability to innovate because we were the first of the team who has discovered daridorexant, was the first to really go in clinic with a product blocking orexin receptors. This was almorexant at this time. We really are in the middle of innovation. As I have mentioned, what was also very important is not only to have the right concept but to have the right drug. It took us, I think, more than 25,000 drugs to be synthesized in order to discover daridorexant, which is absolutely unique in terms of pharmacokinetics and also pharmacodynamic properties. As you have seen, what is also very important in Idorsia is a patient-focused drug development. This focus on really trying to understand better what is needed for the patient, what is his main issue, what does he suffer, is quite unique.
We did that with ponesimod for fatigue. We are doing that with daridorexant for the daytime performance. We are going to do that with decelevstat for pain and this pain questionnaire . I think it's one characteristic is that we not only go to the simple, or I would say, usual endpoint, but we try to really evaluate what is important for the patient. Finally, even if we are now just starting with a group of Simon Jones, this building of this commercial organization, I think they understand very well what is needed for commercial success. I can tell you, even if we have a very good product and a very good drug, we do not believe that it's going to be selling by itself.
We are getting prepared for this very large effort for this commercial launch because we will need to work very hard to really get the full potential and full commercial potential of this drug. I think that now if I remember you, and I like consistency also not only within two studies but also with what we say. This is the first slide, and this is our strategy as it was explained to the investors who have decided to come with us three years ago when the company was created.
Jean-Paul, we are on slide 20, right? Sorry.
Slide 20. Sorry.
Yeah.
Never mind. We wanted to clearly explain what is our strategy priorities. Number one was, and we were giving us a five-year time scale. First one was to really bring three products to the market. Frankly, I really think that with daridorexant, we will have the first one. We are now working very hard for the other projects, but they are moving also well. That is on a good way, this goal. Number two was clearly to create a commercial organization. This is also on the way. As I mentioned. We wanted to bring Idorsia to profitability. I think that with a drug such as daridorexant, it will give us a very good tool to grow our sales and hopefully to reach profitability in a reasonable amount of time.
We also wanted to create a pipeline with a sales potential, a peak of CHF 5 billion or more. I think that with all our pipeline, we are also on a good way to have the drugs which will allow to reach this goal. Finally, we want to use a state-of-the-art technology. You cannot see that, but this is now true with artificial intelligence that we are integrating into drug discovery. This is true, as I've mentioned, into the new way we are evaluating clinical, how we are making clinical programs. This is what we're going to improve with our launch, which is going to use a lot of digital technology. I think we are moving back on the right direction. We are on a good track, and Idorsia is really in a very good and much better position than ever. Thank you. That's my last slide.
Thank you, Jean-Paul. Next slide, please. Now we're in the position to be able to take your questions. For this part of the call, Martine will be able to join us. Please remember that this is a presentation on phase III data, keep your questions to the topic. Questions on commercialization or on financial numbers, we will be able to address at a later time. Operator, please open the lines.
Thank you. Ladies and gentlemen, we will now begin our question and answer session. If you have a question for our speakers, please dial zero one on your telephone keypad now to enter the queue. Once your name has been announced, you can ask a question. If you find your question has been answered before it's your turn to speak, you can dial zero two to cancel your question. If you are using speaker equipment today, please lift the handset before making your selection. One moment please for the first question. The first question received is from Rajan Sharma of Deutsche Bank. Your line is now open. Please go ahead.
Hey, thanks for the question. I'm just hoping you could help us understand the somnolence rates between the 25 milligram and 50 milligram doses. Obviously, in the first trial, there was a higher rate associated with 25 milligrams versus 50 milligrams, and that seems to be consistent here. Just kind of to get your thoughts on any reasons for this would be really helpful. Secondly, just to clarify, do you expect to get the data from the long-term safety study, so study three oh three, prior to the FDA meeting?
Thank you, Rajan. Guy, can you take those questions on somnolence rates, 50 and 25 milligrams, and your expectations for the 303 data?
Yes. Starting with the 303. Yes, we expect the data to be available prior to the interaction with the FDA. That's not important from an efficacy perspective, but it's important from a safety perspective because as part of this 303 study, we have a sufficient amount of patients treated for up to a year. Of course, as we are looking for a chronic indication, we need this data. That will be available. The second question is about insomnia, sorry, somnolence, and the lack of dose response. I think it's an interesting observation. It's very difficult to comment on very low numbers. The message for me is more that we have very low level of somnolence across all dose levels.
It's probably in keeping with the pharmacokinetic of the product and the fact that the half-life is reasonably short, ideal for an insomnia product, and therefore the patient would not feel somnolence during the day and not report somnolence as an adverse event very frequently. We see very few, and what is also very interesting for us is to see that there is certainly no more patients with somnolence at 50 milligrams than at 25 or 10. Therefore, I think having now shown that 10 milligrams doesn't provide much benefit and 50 providing more benefit, it gives us a good chance to maybe achieve the right dose in our labeling.
Thank you, Guy. Next question, please.
The next question received is from Graig Suvannavejh of Goldman Sachs. Your line is now open. Please go ahead.
Hey. Good afternoon, good morning, and thanks for taking my questions. I was curious, and I might have missed it, my apologies, but did you look at next day performance? I know that was one of the key attributes that you highlighted, in study 301 and just wondering if it was measured, what you saw in next day performance. That'd be my first question. Then my second question really has to do around what doses, just to confirm what doses you do plan on filing and do you expect to get differential claims for both doses or What's the thought on kind of what you think the label's going to look like? Thanks.
Thank you, Graig. Guy, I think both questions are for you, the one on next day performance as well as our filing thoughts.
On the first question first. Before answering the question, I would like to be sure that we talk about the same thing, which is daytime performance. There is a bit of semantic here, of course. I do not want to be too complicated, but there is also the issue of next morning residual effect versus daytime functioning. I believe what you are talking about is the daytime functioning using the IDSIQ questionnaire that we have developed and validated. The question was about the effect that we observed, right?
Yes. Can you describe without giving the numbers?
Yeah.
Is there an effect? How is the effect?
Yeah. This questionnaire is made of three domains. I would refer you to the previous presentation where this is described. Presentation that is still on our website. One domain is the sleepiness domain, which has a number of questions within that I also described on the slide that I presented last time. This is the one that we use as secondary endpoint. We demonstrated that on 50 milligrams, there is a very highly significant effect on this domain. We have not disclosed the numbers, but I can tell you that as part of the development of the questionnaire, we also validate what would be clinically perceived by the patient, what would be clinically relevant. On this domain, we can claim that the effect we observe is clinically important for patients.
We have not reported on other domains, but I can also reassure you that there is consistency of the other domains. One was called the alert cognition domain. The other one was the mood domain. Of course, there is this overall questionnaire. Without disclosing the data, I can tell you that it's very consistent across the three domains and the total score on 50 milligrams. Now turning to 25 milligrams. What we observe is a numerical effect, which is not too distant from the 50 milligrams, that it's in between placebo and 50 as you would expect. In the second study, we have actually very similar results of the 25 milligram on this questionnaire. There is total consistency of the 25-milligram effect on the daytime performance.
As I didn't mention before, but it's in our press release, we are going to complete the analysis of this program by combining the treatment groups that we can combine for the two studies through a pooled analysis, and these are the 25-milligram groups and the placebo groups. I'm very confident that by pooling the two studies together on the different endpoints, we will have extremely good and precise estimates of the effect of the 25-milligram dose, including on this daytime performance. Now turning to the second question. I would be speculating on what we are going to decide in the next weeks and months. I can do that. What is more difficult is to speculate on what the FDA will tell us, because I'm not part of them.
Certainly, our intention is to take advantage of the lack of efficacy demonstrated of the very small efficacy, I would say, of 10 milligrams, the good efficacy of 25, and the very good efficacy on 50. Saying that is giving maybe a bit of a light on our idea of trying to put out in our submission to go with 25 and 50 milligrams. Of course, this will also depend on the interaction we'll have with the FDA later in the year and how they react to our data. The final dose that will be labeled will be known once we have this drug approved.
Okay. Thank you. If I could just have a follow-up. I believe Dayvigo is approved in 5 and 10 mg, and BELSOMRA is approved at 5 mg to 20 mg. Do you have a perspective at this point in time, given the data that you've seen about how daridorexant compares across the two other approved DORA products in terms of efficacy?
Yeah. This is of course a question that we are of course debating and looking. I would maybe tell you two things. One is versus suvorexant, which is the most recently approved. If you look at the labeling, the data are presented in such a way that it's very difficult to know exactly in terms of minutes by how much the treatment effect is. This makes the comparison very difficult. Having said that, we can have estimates, and certainly on the night assessment, we are not inferior at all. What the second part of my answer is that what we have in our program is actually unique. Because not only we could see an effect, which I believe is at least, during the night, as good as what is seen with suvorexant and lemborexant. We are adding a new dimension in our database, which is the daytime assessment.
Nobody has ever developed an instrument that is as comprehensive as the one we have. Nobody has done during drug development, assessment of the daytime performance to the level we did it using validated tools, daily measures. We are in a unique situation now to be able to differentiate the product not just in the night, but also adding a new dimension with the daytime assessment. We do that without impacting the safety of the patient. I think your question is about the differentiation. Here, we primarily differentiate the product by the information we have on daytime performance. The safety is very good, which is also in relation to the pharmacokinetic profile of our product. Especially, you would see the data, you have seen the data, you can compare in respect to somnolence and fatigue, for example.
Just if I can add, Guy. Thank you. I think it's very important that people, when you make comparison, and it's true with many drugs, very often you can get a better efficacy with the drug. The problem is to get a better efficacy without impairing the safety or the side effects. I think that what is extraordinary is not really, I would say, that it's much more active or less active than other drug, is that we get an efficacy without side effects or very, very limited side effects. Look at the somnolence rate compared to what is on the label of the drugs you have mentioned. It's always possible to get sometimes to make the patient sleep longer. The problem is that they sleep not too longer. That's the issue. If you compare only the quantity of sleep, this is really not helpful.
What is important is the quantity of sleep and people being able to wake up in good shape. I would say that is the most important that the people have to remember.
Excellent.
Okay, thank you all.
Thank you, Jean-Paul. Thank you, Graig.
Operator, next question, please.
The next question we'll receive is from Nick Nieland of Citi. Your line is now open. Please go ahead.
Hello, thanks for taking the questions. The first one is about the pooled analysis. How long will that take, and will you publish the results of that? Will we see anything from that pooled analysis, before you file? Just a quick question on suicidal ideation. Although the numbers were tiny, one patient in each dose. Dayvigo has actually got a warning on the label with a similar rate, i.e., 0.3%. Do you think that you are likely to get a warning on label or if there's any comment you can make on that? Thank you.
Thank you, Nick. Guy, I think those two are again for you.
Yeah.
Some indication on the pooled analysis as to how long it is going to take us and when will we have it before the filing, and then comments on the suicidal ideation.
Yeah. The pooled analysis is ongoing. As you can imagine, number one, that was pre-planned, so there is no ambiguity about that. It's ongoing. Of course, it's a bit delayed compared to the primary analysis of the study because we prioritize the 302 results before doing the pooled and communicating on that. It will take a while to have the complete data set analyzed in a pooled fashion. Therefore, this will come during summer. In terms of publishing it, of course, we'll publish. Whether we publish that before filing is difficult to say because we are not mastering the willingness of editors to publish quickly. We will certainly make an effort to communicate in congresses as much as we can, as early as we can. I can't guarantee that it will be done before filing.
We would like to prioritize the filing over everything else because we think that that's the best way to make the drug available to patients as quickly as possible. If we can have publications before, that would be great, but I cannot guarantee that. On the suicidal ideation, I think it's very difficult to make conclusions. You see that there are a handful number of events, one hand even, not more than four. What it means is difficult to assess. I cannot tell you what the FDA will say, but I'll be surprised if they just ignore it completely. We may be treated as every other product of that class and have the same kind of warning. That's a possibility. These effects exist.
I don't think they are problematic, but the FDA rightly is often conservative in terms of what is in the labeling, just to make sure that physicians and patients get the right information.
I think also, Guy, what is going to be interesting is the mood. We have a very thorough analysis of the mood effect of the drug, and I think it will be put in context. As you said, there is always the possibility to stay safe, but what is important will be the analysis of the effects of this drug on mood.
By that, Jean-Paul, I think you refer to the mood domain of the IDSIQ questionnaire.
Exactly.
Right. Which, as I mentioned earlier during this call, provides some very, very good data that we cannot disclose numerically, but the data were really very, very good in the first study. I don't have the results today of the second study, but the first one was very good.
Great. Thank you.
Excellent. Thank you, Nick. Operator, next question, please.
The next question received is from Barbara Blaha of Credit Suisse. Your line is now open, madam. Please go ahead.
Thank you for taking my question. I have two questions. One actually relates to the type 1 error, which you mentioned in the press release. Could you please elaborate on the type 1 error and where it exactly occurred? Whether you falsely rejected a positive or just give some details to this. If you pool the data together, how do you construct these three? You don't have 16 comparisons, but only 12. You just take off a part or Yeah. Could you please elaborate on this?
Yes. I thought I was too long on the type 1 error control in the presentation. I spent probably 10 minutes on that slide. I do not want to repeat everything I said. What matters is that the type 1 error was controlled across the entire study. Of course, as you can see, we didn't reject the hypothesis on LPS in the second study. We rejected the first one, which was called H2, I believe, on that slide. It limits the propagation of the alpha level downwards. It doesn't stop at all the analysis because H1 was rejected. That was a bit different from the first study where there was no rejection at all of H1 and H2, and many others as well. I believe if you want more details, rather than to spend, again, a few minutes, maybe we can have a separate phone call.
I would offer that to you. On the pool, we don't have a typical alpha level control. The purpose of the pool analysis is primarily to get the more precise estimate of the treatment effect on 25. We can have a separate call because I think it can be quite complicated doing this.
Okay. I will call you later. Sorry, one more question. If the data of the pooled analysis will not reach statistical significance, will you nevertheless file with the data that you have now or
Right. Yeah. This is a scenario that honestly I would reject completely. I cannot believe that at all based on the data that I've seen. I'm sorry that I cannot give you more because of the limitation due to the scientific integrity of the publication. We do not want to give P values. We do not want to give actual numbers. If you had seen what I've seen, you'll be immediately convinced that the likelihood of the scenario you describe is extremely unlikely, and I wouldn't even consider it.
Okay. Good.
I hope you can believe me. Please trust me that I can tell you.
I will call you later.
Yeah.
Thank you.
Please do.
Thank you, Barbara. Thank you, Guy. Operator, next question, please.
Okay, before we take the next question, just a reminder, if you would like to ask your question, please press zero one on your telephone keypad now. The next question received from Stefan Schneider of Bank Vontobel. Your line is now open. Please go ahead.
Yes. Hi. Thanks. Guy, you said that in comparison to the other two DORAs on the market, you would say the night data you have seen is not impaired compared to them. In my view, the way I look at it, that some of the label issues with the other two DORAs is more during the daytime. Next day, the next day hangover effects, including driving. My first question is, can you comment on that in comparison to the other two? The other one is, I think you have done a driving study. Will we see the data, and if so, when? Thank you.
Hi. Thank you. This is a recurrent question. I am pleased that you ask it again today. Daytime, we have a very strong assessment for the daytime the next morning, to use the right terminology, the morning effect. We did that by having a special collection as part of the SDQ questionnaire. There is one question that is specifically collecting information from the patient as to whether they feel sleepy or not in the morning. We have not, again, communicated visually on slides on Sunabared, but I can comment. We do not see any sleepiness on average in this population. They tend to have less sleepiness on treatment compared to baseline. That was done without treatment. As we increase the dose, we even see less with higher dose than lower dose and less with placebo.
Overall, based on the entire data that we have, and just to remind you, we have 1,800 patients in the study. The two studies, including 1,200 on the dose on daridorexant 10, 25, and 50 milligrams. Across this entire database, what we see is that there is absolutely no impairment of the next morning effect. There is no hangover effect, as we couldn't detect any hangover effect based on this specific questionnaire. If we see a trend, it was of the opposite, that they feel better in the morning, less sleepy in the morning, probably because they had actually a better night. The driving study is done in the same situation, but in a very, very different population because as you know from the guidelines, it's done in a healthy population.
We are going to report later in the year on the totality of the clinical pharmacology program. We have done a very comprehensive clinical program looking at a number of aspects. Of course, the drug-drug interactions, but also the pharmacokinetic in different populations like liver impairment, we have impaired patients, but also the safety in specific populations like patients with obstructive sleep apnea as well as COPD patients. Of course, we have done the drug abuse study and the driving studies. We would like to communicate globally on this program rather than studies one by one. They are all extremely important to really define the safety profile of the product, we do not want to just communicate on one and then another one, and then the third one. Stay tuned. We will certainly talk about it in the near future.
Thank you, Guy. Thank you, Stefan. Operator, has anybody enlisted in for further questions?
No, actually, we received no further questions.
All right. Thank you very much. We're coming to the end of this call. Thank you for your ongoing interest and support of Idorsia. We are on an exciting journey, so stay tuned. Next planned communication release is for the July 23rd, when we will be discussing first half financial performance. Stay safe and stay healthy. Goodbye, everyone. Operator, you can close the lines.
Yeah, ladies and gentlemen, thank you for your attendance. This call has been concluded. You may disconnect.