, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.
The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).
Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”
“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.
Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.
Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.
FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.
Forced awakening
Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.
“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.
FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.
It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.
The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.
Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.
Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.
Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.