Phase 3 Studies on Daridorexant for Treatment of Sleep Disorders


Drs Wendy Wright and Debra Davis provide an overview of phase 3 trial data for the most recently FDA-approved DORA, daridorexant, for the treatment of insomnia.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: The newest one on the market is the drug called daridorexant. Because it’s so new, and it was approved in May of 2022 by the FDA, let’s spend a bit of time talking about this trial and the trial to get it approved. I’m going to summarize and then I’m hoping you and I can have a bit of a conversation about it. They did 2 blinded placebo-controlled trials. They were 12-week trials. There was even an extension trial for an additional 40 weeks to assess for safety. But you brought this up, they also assessed for tolerance and withdrawal symptoms, is that correct in that extension trial?

Debra Davis, CRNP: That is correct.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: Then they studied 3 different dosages at 10, 25, and 50 mg. The 10 mg was not FDA approved, so what our colleagues have available out on the market today is 25 and 50 mg. Is that correct so far?

Debra Davis, CRNP: That is correct, and what I liked in talking about this drug and looking at this study, is so many times patients will come to us, and they’ll say, “I’m very sensitive, you need to prescribe to me the lowest dose.” Not really. In the study, a lot of times 25 mg did not meet the goal of staying asleep longer. It did well, it did better than the placebo, but not as good as the 50-mg dose did. The company will tell you there is no starting dose, you can start at 25 mg or you can start at 50 mg. But if you want your patient to be successful, you want to start at the 50-mg dose. Of course, there’s always the problem if someone has liver disease or is on one of the other medications that are contraindicated, then you’ll start at the 25-mg dose, but 50 mg should be the dose. It is the dose in the study that showed the most efficacy.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: I struggle with that, having prescribed this a fair amount as well, because it goes against the grain of me as an NP [nurse practitioner]. We’ve all been taught to start low, go slow. But when you look at the adverse events in the clinical trials, the 50 mg really wasn’t any higher than the 25 mg yet the 50 mg showed statistical significance in all 3 of the metrics, which was time to fall asleep, as well as the time awake after sleep onset. We call that WASO [wakefulness after sleep onset]. Then it also looked at total sleep time. What I loved about this was it wasn’t polysomnography; it was patient reported. So not only did we see the objective data that you talked about and how important that is, but we also saw that patients felt like they slept an additional almost 1 hour in the middle of the night, and that was their perception.

Debra Davis, CRNP: I thought that was so important that the patients were happy with the drug, and they were happy that they got that extra hour of sleep because in the study when you look at it, these people were sleeping less than 5 hours. For somebody to get to that 6-to-7-hour mark and never having been there in 10 years, they feel like they have a new lease on life, and they should.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: Absolutely, and we started this tonight by saying we focus so much on nighttime sleep. But I think what we also need to focus on is the daytime metrics. For the first time ever, correct me if I’m wrong, but I haven’t seen this before, in addition to looking at nighttime outcomes, they also looked at daytime. And what they found was that the 50 mg produced a reduction in what’s called the IDSIQ [Insomnia Daytime Symptoms and Impacts Questionnaire] in the sleepiness domain, where they looked at mental energy and physical energy. Essentially, they had a clinically meaningful reduction in their sleepiness score the next day.

Debra Davis, CRNP: What I found so impressive was they made them fill this out every night, so it wasn’t, “How did you sleep last night,” but, “How did you feel today? Were you mentally tired, were you physically tired, were you sleepy?” If you look at me and say, “Are you mentally tired, are you physically tired?” I would say, “Yes, I am. It’s 9 or 10 o’clock at night.” For them to have improved that IDSIQ score, they were looking at a reduction of 4, and for them to have met that mark and have that reduction of 4 points, just by patients telling you what they felt the night after they were judging their day, to me is very impressive.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: Absolutely, and the last thing I think we should chat about is that in that 40-week trial, they continued to improve. We didn’t see tolerance here; we saw that their IDSIQ scores held at least, if not improved. So, one could argue, and this is where there’s some discussion in the world of insomnia, when you start helping people to sleep, and they’re filling that sleep bank up because they’re having a successful night every night they go to bed, will that continue to improve their overall mood, their sleepiness moving forward over time? I think we need more studies to show that, but I think this was the first pharmaceutical agent we’ve seen come to market with not only nighttime data but also daytime performance data as well.

Debra Davis, CRNP: It was the first one, and this company came up with the IDSIQ score. I think we should talk a bit about exactly what that was if you want to.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: I’m happy to if you want to jump in.

Debra Davis, CRNP: It’s a word that no one knows what it is.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: I think it was developed along with some FDA guidance, and it’s been deemed reliable and valid. It was developed with the FDA as a metric to be used to test insomnia medicines in terms of 4 different types of domains.

Debra Davis, CRNP: The word IDSIQ stands for Insomnia Daytime Symptoms and Impacts Questionnaire. It’s a daytime sleepiness score, correct?

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: Yes.

Debra Davis, CRNP: It was, “How you are feeling the next day,” and this company developed it, took it to the FDA, and got almost unheard-of FDA approval for this scoring mechanism to rate their own drug, not knowing how it would rate. I’m sure they felt excited about it and thought that it would rate well, but it worked out well for them that they came up with their own scoring system, and then it was found to be very advantageous.

Transcript edited for clarity

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