Long-Term Safety of Once-Nightly Sodium Oxybate for Narcolepsy: RESTORE Study Interim Analysis of Data

Long-Term Safety of Once-Nightly Sodium Oxybate for Narcolepsy: RESTORE Study Interim Analysis of Data

Background:

Clinical practice guidelines recognize sodium oxybate (SXB) as a standard-of-care treatment for adults with narcolepsy.^1,2 The pivotal phase 3 REST-ON trial (NCT02720744) evaluated the efficacy and safety of a once-at-bedtime oxybate (LUMRYZ™ sodium oxybate for extended-release oral suspension, CIII [FT218; once-nightly sodium oxybate (ON-SXB)]) for treatment of adults with narcolepsy.³ In REST-ON, ON-SXB met its 3 coprimary endpoints: improvement in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating (% much/very much improved), and number of weekly cataplexy attacks at all doses tested (P< 0.001 vs placebo). The safety profile of ON-SXB was consistent with that of immediate-release (IR) SXB. 

Purpose/Objectives: The ongoing RESTORE trial (NCT04451668) is an open-label/switch study evaluating the safety and tolerability of ON-SXB.

Methods:

Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive were eligible for RESTORE. Initial doses were 4.5 g/night or equivalent/closest to the previous total IR oxybate dose/night for those switching; incremental adjustments (1.5 g/week; maximum dose, 9 g/night) were allowed. Safety data for participants receiving ≥1 dose of ON-SXB as of 06 March 2023 are reported here.

Results: This analysis includes interim data from 180 participants (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]); mean age is 35 years (range, 16–84). Most participants who reported an adverse event (AE; n=133 [73.9%]) had AEs that were mild (38.9%) or moderate (27.2%) in severity. Fourteen participants experienced a severe AE, 12 participants experienced an AE leading to discontinuation, and 7 participants reported experiencing a serious AE (none occurred in >1 participant). Adverse drug reactions (ADRs; ie, AEs related/possibly related to study drug) were reported by 93 (51.7%) participants. ADRs occurring in ≥3% of participants were nausea (13.3%), somnolence (7.8%), enuresis (6.7%), headache (6.7%), dizziness (5.6%), somnambulism (5.0%), anxiety (3.9%), vomiting (3.9%), paresthesia (3.3%), and tremor (3.3%).

Conclusions: Interim data from the RESTORE study suggest that the safety profile of ON-SXB is consistent with that of SXB. ON-SXB is generally well tolerated, and no new safety signals have been observed thus far in RESTORE.

References: 1. Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881-1893. doi:10.5664/jcsm.9328
2. Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. Eur J Neurol. 2021;28(9):2815-2830. doi:10.1111/ene.14888
3. Kushida CA, Shapiro CM, Roth T, et al. Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. Sleep. 2022;45(6):zsab200. doi:10.1093/sleep/zsab200