Patient Preferences and Nocturnal Experiences With Oxybate Therapy for Narcolepsy: RESTORE Study Interim Analysis

Patient Preferences and Nocturnal Experiences With Oxybate Therapy for Narcolepsy: RESTORE Study Interim Analysis

Background: Sodium oxybate (SXB) is a standard-of-care treatment for adults with narcolepsy.^1,2 First-generation, immediate-release (IR) oxybate formulations require patients to awaken for a second dose 2.5–4 hours after the first bedtime dose. Once-nightly SXB (ON-SXB; FT218; LUMRYZ™), an extended-release formulation of SXB, replaces this middle-of-the-night dosing with a once-at-bedtime regimen.

Purpose/Objectives: RESTORE (NCT04451668) is an open-label/switch study evaluating the safety/tolerability of ON-SXB and patient preferences for ON-SXB or IR oxybate.

Methods:

RESTORE includes participants aged ≥16 years with narcolepsy type 1 or 2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive. Initial doses for participants switching from IR oxybate are equivalent/closest to the previous total dose/night; incremental adjustments (1.5 g/week; maximum, 9 g/night) are allowed. A nocturnal adverse event (AE) questionnaire about switch participants’ IR oxybate experience in the previous 3 months was completed at baseline. Switch participants completed the preference questionnaire after 3 months of ON-SXB treatment.

Results: Data available from preference questionnaires (n=98) and nocturnal AE questionnaires (n=130) were analyzed at the interim data cutoff (06 March 2023). Most common treatment-related AEs thus far were nausea, somnolence, enuresis, headache, dizziness, and somnambulism. The once-nightly dosing regimen was preferred by 93.9% (92/98) of participants. In the previous 3 months, the second nightly IR oxybate dose was unintentionally missed by 84 (65.1%) switch participants and/or was intentionally missed by 26 (20.1%); 80.0% (72/90) who intentionally and/or unintentionally missed the second dose felt worse the next day. Participants who took their second nightly IR oxybate dose >4 h after the first dose (n=51 [39.5%]) reported being somewhat, quite a bit, or extremely groggy/unsteady the next morning (26/51 [51.0%]). Inconvenience of the second dose was reported by 71.3%. Other issues related to the second dose were anxiety (30.2%) and the need to be woken by someone else (23.3%). In the past 3 months, 120 participants (93.0%) arose from bed after waking to take the second dose; 9 of these participants reported having fallen, with 5 reporting injuries.

Conclusions: These interim RESTORE data show that 94% of patients switching from twice-nightly IR oxybate have stated a preference for the ON-SXB dosing regimen. Among participants who switched from twice-nightly IR oxybate, a high proportion had difficulty with either taking the second oxybate dose at all or taking it at the right time, which led to feeling worse than usual and/or groggy the next day. ON-SXB, the only once-at-bedtime oxybate, provides a major advancement in patient care and may ease treatment burdens associated with the second nightly IR oxybate dose.

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