Phase III REST-ON trial of FT218 in narcolepsy published in CNS Drugs journal

FT 218, also referred to in Avadel’s scientific publications as ON-SXB, is the Company’s lead drug candidate, an investigational formulation of sodium oxybate designed to be taken once at bedtime for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy.

Approximately 65% of people with narcolepsy are estimated to have nocturnal sleep disturbances. While people living with narcolepsy may be able to fall asleep easily, their sleep tends to include frequent arousals and stage shifts and is often not refreshing. Most treatments for narcolepsy are taken in the morning to combat EDS; only oxybate treatments are taken at bedtime, with current immediate-release formulations taken twice nightly. To evaluate the potential for improvement on sleep architecture with a single bedtime dose of FT 218, secondary endpoints from the double-blind, placebo-controlled REST-ON trial were assessed, including polysomnographic measures of sleep stage shifts and nocturnal arousals. In addition, patient-reported assessments of sleep quality and refreshing nature of sleep, as measured on a visual analog scale, were analyzed. At all doses evaluated (6, 7.5 and 9 g), once-at-bedtime FT218 demonstrated a statistically significant decrease in the number of transitions from stages N1, N2, N3, and rapid eye movement (REM) sleep to wake and from N2, N3, and REM sleep to N1 (P<0.001 at all doses) and number of nocturnal arousals (p><0.05 at 6 g; p><0.001 at 7.5 and 9 g) compared to placebo. sleep quality and refreshing nature of sleep were significantly improved with all evaluated doses compared to placebo (p><0.001). a post-hoc analysis showed that significant improvements in dns were observed regardless of concomitant stimulant use.

Additional post-hoc data further supported improvements in sleep architecture with increases in N3, or slow wave sleep and increased REM latency. The primary safety and efficacy results from REST-ON were published in August 2020 in SLEEP by Kushida et al. The most common adverse events (incidence > 5% and greater than placebo) in patients receiving FT 218 were nausea, dizziness, enuresis, headache and vomiting. Additional secondary and post-hoc data were presented at SLEEP (the annual Meeting of the Associated Professional Sleep Societies) and World Sleep.

See: “Effect of FT218, a Once-Nightly Sodium Oxybate Formulation, on Disrupted Nighttime Sleep in Patients With Narcolepsy: Results From the Randomized Phase 3 REST-ON Trial,” Thomas Roth et al,. CNS Drugs (2022). https://doi.org/10.1007/s40263-022-00904-6