Real-World Data on the Benefits of Once-Nightly Oxybate in Narcolepsy Management

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Once-nightly oxybate (Lumyrz; Avadel Pharmaceuticals), initially approved in 2023 for adults with narcolepsy to treat excessive daytime sleepiness and cataplexy, had its indication expanded in late 2024 to include patients aged 7 years and older.^1,2 Researchers presented new findings from the multicenter observational REFRESH study, assessing the efficacy, satisfaction, and safety of once-nightly sodium oxybate, at the 2025 World Sleep Congress, held September 5-10, in Singapore.³

The goal of REFRESH is to understand more about the real-world experiences with once-nightly sodium oxybate, as well as gain insights for decision-making between twice-nightly and once-nightly solutions. Recently, NeurologyLive^® held a roundtable discussion with 2 sleep experts who talked about the real-world data from the REFRESH study presented at the Congress. Panelists in this conversation included Gerard J. Meskill, MD, the founder and CEO of Tricoastal Narcolepsy and Sleep Disorders Center in Sugar Land, Texas, and Laura B. Herpel, MD, a sleep physician at Bogan Sleep Consultants in Columbia, South Carolina.

In this first episode, Meskill and Herpel reflected on the clinical impact of once-nightly sodium oxybate in patients living with narcolepsy. Both experts noted significant improvements in patient adherence and daytime functioning compared with twice-nightly dosing, as well as reduced disruption to sleep schedules and partner involvement. They emphasized that the findings underscore the importance of simplifying treatment regimens to enhance quality of life and maintain therapeutic efficacy across both type 1 and type 2 narcolepsy patient populations.

Transcript edited for clarity. Click here to view more of our coverage on sleep disorders.

Isabella Ciccone, MPH: Thank you both for coming here today to talk a little bit more about the World Sleep Congress that was recently held this year, and specifically to talk about some of the data presented for narcolepsy management. So, the first question that I have for our discussion here is: what key findings from some of the presentations stood out to you in terms of improving narcolepsy care?

Gerard J. Meskill, MD: One of the interesting abstracts that we saw and participated in was the REFRESH trial, which was looking at the usage of once-nightly sodium oxybate for patients with narcolepsy. As many will know, until very recently, oxybate was a twice-per-night medication, up until the advent of Lumryz in 2024. And so, now that there is a once-nightly variant, it was very interesting to see some of the real-world data associated with that, and how folks would do when they don’t have to wake up to take a dose in the middle of the night.

Laura B. Herpel, MD: I agree. I think we’d already seen some impact and effectiveness of once-nightly oxybate in the RESTORE trial, previously. So, the REFRESH study was refreshing to see real-world data presented. It's a survey of participants that were enrolled—I think it was between July of 2024 up to July of 2025—and, of course, some of the interim analyses were presented showing a real-world impact of once-nightly oxybate, both in patients who had switched from twice-nightly and in patients who were not switching, or were naïve to oxybate. So, we could compare the differences in some of the outcomes between those patients who switched and those who didn’t switch.

And I guess one of the interesting things that I noticed was a lot of the quality-of-life data that was presented and asked about in the study was pretty impressive, and the impacts on other potential comorbid conditions. Those factors were very impressive, and again, reiterating some of the data about patients’ compliance with the once-nightly versus twice-nightly dosing, and how it impacted their life in terms of having to take the medicine twice a night versus once a night—it was impressive.

Gerard J. Meskill, MD: Yeah, I would echo what Herpel said there. I thought it was really interesting looking at the data on just how many people reported missing that second dose. Because, I don’t know about you, Herpel, but prior to a year ago, I wasn’t asking my patients on oxybate how often they were missing a dose. And so, it was striking to see how often that actually happens.

I think probably the reason why—because I’m not going to put you on the spot on that—but what was the alternative, right? If they were missing it or not missing it, we’d just say, “Okay, well, try the best that you can to take it.” But when you look at that—80%, I think, said that they missed a dose at least some of the time, and half said they missed it at least once a week. And almost all of them said that when they missed a dose, they had worsening sleepiness. It really does, for at least those individuals, create a significant barrier to getting the most effective therapy that they can for their narcolepsy.

Laura B. Herpel, MD: Right, I would agree with that. I do approach my patients on oxybate now, and I’ll ask them, “How often are you missing the second dose?” And sometimes, when you phrase it positively—“How often are you able to get both doses in?”—it comes across as being less challenging, and patients will be more honest with me about it.

But I think I didn’t realize how often, even during titrations, when I was trying to titrate up medications, how often patients were missing. I might have been titrating too quickly because they were missing their doses, and the timing differences that they would have night to night. And I understand how that can be important for some individuals—to have that tight control with the twice-nightly dosing. But the outcomes when some of my patients were switching were impressive based on this data, both for patients that switched and those that didn’t.

The other interesting concept was the data from some of the partners. I know there wasn’t a lot of partner data, but when you look at the impact on the partner’s quality of life—because they’ve got to wake up too—and I hadn’t really asked my patients that before, like, “Is your spouse waking you up?” I mean, sometimes they’ll tell me that, but I saw some statistic that said 48% of the participants relied on someone to wake them up for their second dose a few times a week. And I didn’t realize it was that many who did that.

Gerard J. Meskill, MD: And I think that’s an important point, because we don’t really think about the social implications of treatment sometimes. If your treatment requires your significant other, your partner, or a family member to have to wake up in the middle of the night exclusively because they need to help you get your treatment, there probably is some degree of guilt that’s associated with that.

I’m sure that at least in some instances, folks may look at it and say, “Well, do I really need to involve my significant other tonight? They’ve got a big day tomorrow,” and may put off the possibility of getting their second dose—or just try to do it on their own and not set their alarm because they’re worried about disturbing somebody they care about. And we don’t think about that, but that’s a really important point. I’m glad you brought it up.

Laura B. Herpel, MD: Yeah, and I think that this data really showed us the difference in the social implications of individuals’ quality of life, their partners’ quality of life, and a lot of data on disability issues as well. The Sheehan Disability Scale was brought up too, which we don’t always see as an outcome in real-world data.

Because, I mean, I ask my patients, “How’s your family life? How’s your quality of life? Are you able to do anything after work? Or are you just going home and crashing?” But to see it in numbers and see improvements across the board—in their work, family life, and social life—I think it was nice to see changes in both patients who were switching from twice-nightly and those who were naïve.

It just goes to show you: oxybates really work. They really work to help improve functionality—not just sleepiness, but functionality—in patients who have narcolepsy. This was a combination of both type 1 and type 2, with more type 2 patients in this study. Everybody thinks type 2 might be a milder form of narcolepsy, but it’s not. I mean, it just means no cataplexy, right. They’re still super sleepy individuals, and their functionality is impacted significantly. So, I think it’s really nicely representative of a lot of patients with narcolepsy.

Gerard J. Meskill, MD: I would agree with you. I think there are data that came out more recently looking at computer-site data of narcoleptics. Despite treatment, both type 1 and type 2 patients did complain that they had residual excessive daytime sleepiness. I think the complaint from type 2 was actually a higher percentage than type 1, even. So, I agree with you. I think that sometimes type 2 gets pushed off as the redheaded stepchild of narcolepsy, but their outcomes are important too—and they suffer just as much.

REFERENCES
1. Avadel Pharmaceuticals announces final FDA approval of Lumryz (sodium oxybate) for extended-release oral suspension as the first and only once-at-bedtime oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy. News release. Avadel Pharmaceuticals. May 1, 2023. Accessed November 5, 2025. https://www.globenewswire.com/news-release/2023/05/01/2658536/0/en/Avadel-Pharmaceuticals-Announces-Final-FDA-Approval-of-LUMRYZ-sodium-oxybate-
2. Avadel Pharmaceuticals Announces FDA Approval of LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension (CIII) for the Treatment of Cataplexy or Excessive Daytime Sleepiness in Patients 7 Years of Age and Older with Narcolepsy. News Release. Avadel Pharmaceuticals. Published October 17, 2024. Accessed November 5, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-fda-approval-lumryztm-sodium
3. Avadel Pharmaceuticals to Present New Data on LUMRYZ™ (sodium oxybate) for Extended-Release Oral Suspension at World Sleep 2025. News release. Avadel Pharmaceuticals. September 5, 2025. Accessed November 5, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-present-new-data-lumryztm-sodium-0