Meta-Analysis Confirms Efficacy of Sodium Oxybate in Managing Narcolepsy Symptoms

Findings from a recent meta-analysis of randomized controlled trials published in Sleep and Breathing reinforced the efficacy of the FDA-approved narcolepsy therapy sodium oxybate for patients living with the sleep disorder, particularly in managing cataplexy and improving daytime wakefulness.¹

In the analysis, treatment with sodium oxybate resulted in a significant reduction in weekly cataplexy attacks compared with placebo (mean difference [MD] = -5.04; 95% CI, -6.35 to -3.72; P <.00001). Measures of wakefulness and sleepiness also improved, with notable gains observed in the Maintenance of Wakefulness Test (MD = 4.66; 95% CI, 2.24 to 7.07; P =.0002) and Epworth Sleepiness Scale (ESS) scores (MD = -1.93; 95% CI, -2.73 to -1.13; P <.00001). Global clinical improvement, measured by the Clinical Global Impression-Improvement (CGI-I) scale, was more than twice as likely reported in sodium oxybate-treated patients (risk ratio [RR] = 2.15; 95% CI, 1.69 to 2.73; P <.00001).

Conducted by lead author Ahmed Mostafa Amin, a medical student at Al-Azhar University in Egypt and researcher at Negida Academy LLC, and colleagues, the study included data from 5 randomized controlled trials that assessed sodium oxybate’s effectiveness and safety among patients with narcolepsy. Participants enrolled across the trials in the treatment groups received doses ranging from 4.5 gm to 9 gm of sodium oxybate. The primary outcome, reduction in weekly cataplexy attacks, while secondary outcomes included the Maintenance of Wakefulness Test and ESS.

Overall, the dose-response analysis indicated that higher doses of sodium oxybate yielded greater benefits. The 9-gm dose showed the most substantial reductions in weekly cataplexy attacks and significant improvements in both ESS and CGI-I scores. Lower doses, such as 4.5 gm, also provided notable benefits but were less impactful. Adverse events (AEs) were consistent with previously reported safety profiles, supporting sodium oxybate’s tolerability in this patient population. Authors noted that despite the positive results from the analysis, future research may be required to further establish its efficacy and optimize dosing strategies in patient care.

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In May 2023, the FDA initially approved sodium oxybate (Lumryz; Avadel Pharamaceuticals) for cataplexy or excessive daytime sleepiness in adults with narcolepsy after Avadel submitted an amendment to the FDA’s request for final approval.² The initial approval was supported by data from the phase 3 REST-ON trial (NCT02720744). Held under a special protocol assessment agreement with the FDA, the study featured 222 patients with narcolepsy type 1 or 2, all aged 16 years or older, who received uptitration doses of 4.5 g, 6 g, 7.5 g, and 9 g of Lumryz or placebo over the course of a 3-week screening period, 13-week treatment period, and 1-week follow-up period.

The REST-ON trial met all 3 of its primary end points of change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression Improvement, and weekly cataplexy attacks within the 6-, 7.5-, and 9-g groups.³ The data from the trial showed a significantly greater increase in sleep latency with the treatment at week 3 for the 6-g dose group (8.1 vs 3.1 min, respectively; least-squares mean difference [LSMD], 4.98; 95% CI, 2.90-7.05; P <.001); at week 8 for the 7.5-g dose group (9.6 vs 3.3 min, respectively; LSMD, 6.21; 95% CI, 3.84-8.58; P <.001); and at week 13 for the 9-g dose group compared with placebo (10.8 vs 4.7 min, respectively; LSMD, 6.13; 95% CI, 3.52-8.75; P <.001).

In October 2024, the agency approved Avadel Pharamaceuticals' supplemental new drug application (sNDA) for sodium oxybate for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. With this approval, sodium oxybate could reduce the burden on families and caregivers of pediatric patients with narcolepsy who must wake up at night to administer a second dose.⁴ Following this news, Anne Marie Morse, DO, FAASM, the director of Child Neurology and Pediatric Sleep Medicine at Geisinger Janet Weis Children's Hospital, sat down with NeurologyLive^® to share her reaction in an interview.

During the conversation, Morse, also the program director for Child Neurology Residency Program, talked about how the approval of once-nightly sodium oxybate impacts the treatment landscape for pediatric narcolepsy. She spoke about the key safety considerations and common adverse effects when initiating oxybate therapy in children. Moreover, Morse, who also serves as the host of the Sleeping Around the Podcast × NeurologyLive, emphasized the importance of ensuring that access to effective treatments for narcolepsy is not hindered by subjective assessments of severity.

REFERENCES
1. Amin AM, Hassan A, Khlidj Y, et al. Efficacy and safety of sodium oxybate treatment in adults with narcolepsy and cataplexy: a systematic review and meta-analysis. Sleep Breath. 2024;29(1):12. Published 2024 Nov 27. doi:10.1007/s11325-024-03163-5
2. 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 January 23, 2025. https://www.globenewswire.com/news-release/2023/05/01/2658536/0/en/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-Exc.html
3. Kushida CA, Shapiro CM, Roth T, et al. Once-nightly sodium oxybate (FT218) demonstrated improvements of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. SLEEP. 2021; zsab200. doi:10.1093/sleep/zsab200
4. 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 January 23, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-fda-approval-lumryztm-sodium