Once-Nightly Sodium Oxybate Shows Significant Impact on Cataplexy Attacks, Post-Hoc Analysis Shows

Michael Thorpy, MD

After receiving FDA approval in May, new post-hoc data from the phase 3 REST-ON study (NCT02720744) continued to demonstrate the significant impacts of once-nightly sodium oxybate (Lumryz; Avadel Pharmaceuticals) on cataplexy attacks in patients with narcolepsy.¹

Presented at the 2023 SLEEP Annual Meeting, held June 3-7, in Indianapolis, Indiana, findings showed that 43.8% of patients on doses of 4.5 g of once-daily sodium oxybate had at least a 25% reduction in cataplexy attacks after 1 week of treatment vs 26.4% of those on placebo (P <.05). Led by Michael Thorpy, MD, director, Sleep-Wake Disorders Center, Montefiore, and professor of neurology, Albert Einstein College of Medicine, the study also showed that nearly 10% of participants on doses of either 7.5 g or 9 g were free of cataplexy episodes by week 13.

Otherwise known as FT218, the medication is the first and only FDA-approved once-nightly oxybate for patients with narcolepsy. REST-ON, the pivotal trial that led to its approval, featured 222 patients with narcolepsy type 1 or 2, all aged 16 years or older, who received uptitration doses of 4.5, 6 g, 7.5 g, and 9 g, or placebo over the course of a 3-week screening period, 13-week treatment period, and 1-week follow-up period. In the original analysis, the study 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.²

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In the post-hoc analysis, significantly more participants receiving once-nightly sodium oxybate had at least 25%, 50%, or 75% reduction in cataplexy vs placebo at weeks 3, 8, and 13 (6-g dose: ≥25%, 68.5% vs 40.3%; P < 0.001; ≥50%, 38.4% vs 20.8%; P < 0.05; ≥75%, 23.3% vs 4.2%; P = 0.001; 7.5-g dose: ≥25%, 67.1% vs 43.1%; ≥50%, 53.4% vs 25.0%; ≥75%, 32.9% vs 8.3%; all P < 0.001; 9-g dose: ≥25%, 58.9% vs 41.7%; P < 0.001; ≥50%, 49.3% vs 26.4%; P < 0.001; ≥75%, 32.9% vs 15.3%; P < 0.01). During weeks 8 and 13, investigators also observed complete resolution of cataplexy in certain groups (6-g: 2.7% vs 0; P = NS; 7.5-g: 6.8% vs 0%; P <.05; 9-g: 11.0% vs 2.8%; P <.05).¹

In REST-ON, a significantly greater increase in sleep latency with FT218 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).²

At the 2022 American Academy of Neurology Annual meeting, data from the RESTORE study (NCT04451668) open-label extension suggested that patients with narcolepsy type 1 or 2 prefer the once-nightly regimen of FT218 instead of twice-nightly sodium oxybate. Of the 53 individuals who switched from twice-nightly dosing to once-nightly, 92.5% (n = 49) preferred the new regimen 3 months after the switch. Additionally, 93 participants who switched to FT218 had data collected on nocturnal adverse events (AEs), with those findings suggesting that 66.7% (n = 62) unintentionally missed their second dose of the prior twice-nightly regimen, after which 83.9% (n = 52) reported feeling worse the next day and 14% (n = 9) feeling the same.

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REFERENCES
1. Thorpy M, Kushida C, Ajayi A, Dubow J, Gudeman J. Cataplexy response with FT218 (once-nightly sodium oxybate): post hoc responder analysis from the phase 3 REST-ON clinical trial. Presented at: 2023 SLEEP Annual Meeting; June 3-7; Indianapolis, Indiana. Abstract 0575.
2. 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
3. Dubow JS, Roy A, Stern T, Ajayi A, Harsh J, Seiden DJ. Patient Preference and Nocturnal Experience With Sodium Oxybate Treatment for Narcolepsy: Interim Data From RESTORE. Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual. Poster 470.