Dear ladies and gentlemen, welcome to the Idorsia conference call. At our customer's request, this conference will be recorded. As a reminder, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. If any participant has difficulties hearing the conference, please press * key followed by zero on your telephone for operator assistance. May I now hand you over to Andrew Weiss, who will lead you through this conference. Please go ahead, sir.
Thank you, Kai. Good morning, good afternoon, everyone. This is Andrew Weiss, Head of Investor Relations & 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. Therefore, 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, and good morning, good afternoon, everybody. This is a presentation of the second pivotal study of daridorexant, and it's a follow-up discussion as 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 clinical trials of daridorexant in 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're going to describe today looked at the dose of 10 and 25 milligrams of daridorexant. In both studies, we included adult 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. 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 themselves of the daytime functioning using an instrument that is called the IDSIQ, Insomnia Daytime Symptoms and Impacts 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 confirmatory 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 on 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 run-in 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 polysomnography criteria over two consecutive nights, allowing a clear assessment of the baseline. Following this placebo running phase, the patient was randomized at visit four into three groups, placebo, 10 milligrams, and 25 milligrams of daridorexant. This was given to patients for three months, 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 into a single-blind placebo run-out phase of one week, during which we continue to collect daily assessment of sleep as well as the daytime functioning. We also included one placebo night to look at withdrawal symptoms and rebound during this period.
Finally, at the end of the 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 parameters 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 SDQ, 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 rebound and withdrawal.
On the next slide seven, we have now the description of the primary and secondary endpoint and how they were analyzed. Two primary endpoints were defined. These were nighttime primary endpoints looking at the Wake After Sleep Onset by polysomnography. We call that WASO, and 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 night.
We analyzed these endpoints according to the 10 milligrams versus placebo dose, as well as the 25 milligrams versus placebo. We analyzed these endpoints at month 1 and month 3. 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, and so far, we were quiet about it, but it will be 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, 9, 10, 11, 12, 13, 14, 15, and 16. The H1 and H2 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 1. The blue following the green shows the high dose comparison, 25 milligrams versus placebo at month 3.
Then moving on to the right side of the slide, we have this pink showing the low dose, 10 milligrams versus placebo at month one, and the purple part which shows the low dose, 10 milligrams versus placebo at month three. Essentially what we did was to prioritize 25 milligrams or 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 one or high dose month three, low dose month one, low dose month three, then we organize the comparison of the primary and secondary endpoint in a certain way.
We started with WASO LPS, followed by H3, sTST, the subjective total sleep time, followed by the IDSIQ questionnaire, H4. Similarly, H 5, 6, 7, and 8 for the high dose placebo at month three. Then again, H 9, 10, 11, 12 for the low dose of placebo at month one. H 13, 14, 15, and 16 for the low dose of placebo at month three. What I would like to point out as well is that we started with the alpha value type one 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 this 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, H1 and H2 are tested at 0.025. If we can reject the hypothesis one, 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, and 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, at 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 hypotheses. 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 endpoints where you have to win on both of them to claim positive study. Here 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, and 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, but because I've received questions and many opinions about this control of type 1 error across the 16 comparison, 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 920 for 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. The follow-up was the placebo run out. Also, 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 is called the 303 study, is still ongoing, and I'm not in a position to report the data from that study now, so 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 configured. 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 of placebo. 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 3 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 1 month and 3 months. For WASO, it was highly significant at 1 month and 3 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 improvements 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 have the positive data for 50 milligram versus placebo at month one and month three for subjective total sleep time, and similarly for 25 milligrams of placebo. In the new study, the 302 study, we see on 25 milligram of placebo significant improvement at one month and at three months on sTST.
Again, for the 10 milligrams of placebo, there was numerical improvement of a lower magnitude compared to 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 spanning 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 IDSIQ questionnaire and the sleepiness domain.
I think you're on slide 12, Christian, sorry about that. Sorry.
Slide 12. Thank you, Andrew, to remind me that. On slide 12, we see the IDSIQ 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 have sustained from one month to three months. This is in a nutshell the result 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.
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, very few patients that had adverse events leading to premature discontinuation. We see a very, very few 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 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, the 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 on events adjudicated by the safety committee. 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 numbers 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 and LPS at 50 and 25 milligrams in the first study, and for WASO in 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 patients 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, and I will hand over to Jean-Paul Clozel.
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 better possibility, in a better time could be pooled. I think that this program really showed 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 authorities, for the regulatory authorities, and 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, and we are going to meet the FDA this autumn to prepare for this filing. That's the very important point. Now we have to prepare for the launch. 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, and 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 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 pharmacokinetics of one hour, we wanted a shorter half-life, around five to six hours, to allow for getting an effect on sleep onset module without having this morning hangover effect. Of course, there is still this finding about the data. These are outstanding findings. We still didn't 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 is slide 19. I think that what is important is that this program has to be put into the context of our vision in Idorsia. Clearly, it shows our ability to innovate because we were the first. The team was discovered, daridorexant was the first to really go in clinic with a product blocking orexin receptors. It 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 a 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 cenerimod 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 patients.
Finally, even if we are now just starting with a group of science and this building of this commercial organization, I think we 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 with very large efforts 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 the school 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. We told them Jean-Paul, we are on slide 20, right? Sorry. Slide 20. Sorry. Yeah. We wanted to clearly explain what is our strategy priorities. Number one was, and if 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's in a good way, this goal. Number two was clearly to create a commercial organization, which 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, I think 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. This is, and 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 ways we are evaluating how we are making clinical programs.
This is what we're going to improve with our launch, which is going to need a lot of digital technology. I think with this data and validation, we are in a good spot. 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 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 mute the answer 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 reason 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 303, prior to the FDA meeting?
Thank you, Rajan. Guy, can you take those questions on somnolence rates 50 and 25 mg 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 those 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 will not feel somnolent 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 milligram than at 25 or 10. Therefore I think having now shown that 10 milligram doesn't provide much benefit and 50 providing no benefit, it gives us a good chance to maybe achieve the right dose in our labeling.
Thank you. 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. Thanks for taking my questions. I was curious, I might have missed it, my apologies, did you look at next day performance? I know that was one of the key attributes you highlighted in Study 301, just wondering if it was measured, what you saw in next day performance. That'd be my first question. 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 next?
Thank you, Graig. Guy, I think both questions are for you, the one on next day performance as well as our filing thoughts.
Yeah. 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 semantics 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, and 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 is in between placebo and 50, as you would expect. In the second study, we have actually very similar results of the 25 milligrams on this questionnaire. There is total consistency of the 25 milligrams 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 milligrams 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 milligrams 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, and 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 light on our idea of trying to put in our submission to go with 25 and 50 milligrams. Of course, it will also depend on the interaction we will 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 the drug approved.
Okay. Thank you. If I could just have a follow-up. I believe DAYVIGO is approved in five and 10 milligrams, and BELSOMRA is approved at five to 20. 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. Not only we could see an effect which I believe is at least as good as 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, and especially, you would see the data.
You have seen the data, you have compared in respect to somnolence and QUVIVIQ, for example.
Just if I can add, Guy. Thank you. I think it's very important that people, when you make comparison, 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 drugs, 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 drug you have mentioned. It's always possible to sometimes 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's the most important that the people have to remember.
Excellent.
Okay, thank you.
Thank you, Jean-Paul.
Take care.
Have a good day.
Operator, next question, please.
The next question we'll take 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 one 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's 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 ambiguity about that. It's ongoing. Of course, it's a big delay compared to the primary analysis of the study because we prioritize the 302 results before doing the pool and communicating on that. It will take a while to have the complete data set analyzed in a pool 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 publication before, that would be great, 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 it was a 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 on the mood effects of the drug, and I think it will be put in context. As you said, there is always the possibility to say, but what is important will be the analysis of the effects of the drug on mood.
By that, Jean-Paul, I think you refer to the mood domain of the IDSIQ questionnaire?
Yes.
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 we'll take is from Barbora 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 this type 1 error and whether you falsely rejected a positive or just give some details to this. Then if you pool the data together, how do you construct this tree? Because then you don't have 16 comparisons, but only 12. You just take all from 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 reject 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 will confirm that to you. On the good, we don't have a typical alpha level control, and the purpose of the pooled 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 it.
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'd be immediately convinced that the likelihood of the scenario you described is extremely unlikely, and I wouldn't even consider it.
Okay.
I hope you can believe me. Please trust me that I can tell you.
I will call you later.
Yeah.
Thank you.
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 a question, please press zero one on your telephone keypad now. The next question we receive 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 is more during the daytime, so 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? If so, when? Thank you.
Hi. Thank you. This is a recurrent question. I'm pleased that you ask it again today. The daytime, we have a very strong assessment of 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 IDSIQ 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 and so on about it, but I can comment. We don't see any sleepiness on average in this population. They tend to have less sleepiness on treatment compared to baseline. That was done with a treatment. As we increase the dose, we even see less with higher dose than lower dose and 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. Of course, this on-site database, what we see is that there is actually 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. Now, the driving study is done in the same situation, but in a very different population, because as you know from the guidelines, it's done in 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 clin pharm program looking at a number of aspects. Of course, the drug interaction, also the pharmacokinetic in different populations like liver impairment, renal impairment patients. 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 study. We would love 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, and we do not want to just communicate on one and then another one and then a 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?
Actually, we receive 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 23rd of July when we will be discussing first half financial performance. Stay safe and stay healthy. Goodbye, everyone. Operator, you can close the line.
Yeah, ladies and gentlemen, thank you for your attendance. This call has been concluded. You may disconnect.