Avadel Announces Positive Secondary Endpoint Results for FT218 to Treat Narcolepsy

Phase 3 REST-ON Trial data show that the medication demonstrated clinically meaningful improvement in assessments of disrupted nighttime sleep compared with the placebo.

Avadel Pharmaceuticals has announced the publication of positive secondary endpoint data from its phase 3 REST-On trial of FT218, an investigational formulation of sodium oxybate that is designed to be taken once at bedtime for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.1

The findings were published in CNS Drugs, a peer-reviewed medical journal that focuses on the treatment of neurological and psychiatric disorders.1

Most treatments for narcolepsy are taken in the morning to treat EDS, with only oxybate treatments taken at bedtime in current release formulas designed to be taken twice nightly.1

Investigators launched the double-blind, placebo-controlled REST-ON trial to evaluate the potential for improvement on sleep architecture with a single bedtime dose of the drug. They assessed the secondary endpoints, including nocturnal arousals and polysomnographic measures of sleep stage shifts.1

Additionally, the study analyzed patient-reported assessments of sleep quality and refreshing nature of sleep, which were measured on a visual analog scale.1

The study evaluated the 6-, 7.5-, and 9-g doses once at bedtime, and all showed 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, N2 and REM sleep to N1. Furthermore, the doses showed statistically significant decreases in the number of nocturnal arousals compared with the placebo.1

The refreshing nature of sleep and sleep quality were also significantly improved with all evaluated doses compared with the placebo.1

Additionally, a post-hoc analysis showed that significant improvements to disrupted nighttime sleep (DNS) were observed, regardless of concomitant stimulant use. The post-hoc data also further support improvements in sleep architecture with increases in N3 or slow-wave sleep and increased REM latency.1

“DNS is a frequent, bothersome but often minimized symptom of narcolepsy,” Thomas Roth, PhD, director of the Sleep Disorders and Research Center at Henry Ford Hospital, said in a statement.1

“These data show that FT218 improved both objective and subjective assessments of DNS, as measured by polysomnographic recordings and the participants’ own assessments. These results will be relevant for the sleep medicine community to consider in treatment selection, if FT218 is approved,” Roth said.1

The primary efficacy and safety results from the REST-On trial were published in August 2020 in the journal SLEEP.1

The most common adverse events in individuals receiving FT218 were dizziness, enuresis, headaches, nausea, and vomiting. Additional secondary and post-hoc data were presented at SLEEP, the annual meeting of the Associated Professional Sleep Societies and World Sleep.1

All 3 doses demonstrated statistically significant improvement compared with the placebo. With the 9-g dosage, the increase in mean sleep latency was 10.8 minutes compared with 4.7 minutes for the placebo.2

References

1. Avadel Pharmaceuticals announces publication of positive secondary endpoint data from pivotal phase 3 REST-ON trial. Avadel. News release. April 6, 2022. Accessed April 8, 2022. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-publication-positive-secondary

2. Kushida CA, Shapiro CM, Roth T, Thorpy MJ, et al. Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. Sleep. 2021;zsab200. doi:https://doi.org/10.1093/sleep/zsab200