Patients who switched from a twice-nightly stable regimen of Xyrem or Xywav to once-nightly FT218 reported that they preferred the new dosing schedule, along with challenges in adherence to twice-nightly dosing.
Updated data from the ongoing RESTORE study (NCT04451668) open-label extension suggest that patients have a preference for the once-nightly regimen of FT218 (Avadel Pharmaceuticals), an investigational formulation of sodium oxybate designed for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy type 1 or 2.1,2
Presented at the virtual component of the 2022 American Academy of Neurology Annual Meeting, April 24-26, these interim results included data from a cutoff date of February 16, 2022, a further 5 months from the data that were reported earlier in the month (cutoff of September 7, 2021). Of the 53 individuals who switched from twice-nightly dosing to once-nightly, 92.5% (n = 49) preferred the new regimen 3 months after the switch. Additionally, 93 participants who switched to FT218 had data collected on nocturnal adverse events (AEs), with those findings suggesting that 66.7% (n = 62) unintentionally missed their second dose of the prior twice-nightly regimen, after which 83.9% (n = 52) reported feeling worse the next day and 14% (n = 9) feeling the same.1
“Twice-nightly oxybates for narcolepsy require a challenging dosing regimen that disrupts nighttime sleep. The results from the nocturnal AEs questionnaire illustrate the burden that the second dose places on some patients, who already struggle with getting a full night of refreshing sleep,” presenting author Asim Roy, MD, medical director, Ohio Sleep Medicine Institute, said in a statement.2 “In my experience with patients in my practice, a once-at-bedtime option like FT218 would ease this burden and has the potential to be a major advance for the entire narcolepsy community.”
Overall, 76.3% (n = 71) of the switch group reported that the original twice-nightly regimen—specifically the second dose—was somewhat (23%; n = 21), quite (32%; n = 30), or extremely (21%; n = 20) inconvenient to take. Anxiety was reported by 26.9% (n = 25) of the switch cohort, and the need for someone else to wake them was reported by 22.6% (n = 21).
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Additional data showed that 38.7% of (n = 36) patients who completed the nocturnal AEs questionnaire had taken their second dose of immediate-release sodium oxybate more than 4 hours after their first. Of those individuals, 50% (n = 18) related feeling somewhat (22%; n = 8), quite (20%; n = 7), or extremely (8%; n = 3) groggy or unsteady the next morning. Notably, 90.3% (n = 84) of the switch participants reported getting out of bed after awakening to take their second dose, of whom 6 reported having fallen, with 3 instances of injury.
Nausea, occurring in 22.6% (n = 21) of the switch cohort, was commonly reported with a second dose of immediate-release sodium oxybate, while 29% (n = 27) reported other AEs, such as enuresis, nocturnal eating, and somnambulism.
Patients in RESTORE included those who had completed the phase 3 REST-ON trial (NCT02720744) and were receiving a stable dose of immediate-release sodium oxybate (Xyrem; Jazz) or calcium/magnesium/potassium/sodium oxybates (Xywav; Jazz) for at least 4 weeks. The protocol was expanded in May 2021 to include those who were oxybate-naïve as well. Those who switched from stable doses were switched to the closest equivalent dose of FT218, while all others received an initial dose of 4.5 g per night.
“These interim results from the ongoing RESTORE study highlight the preference for the once-at-bedtime versus twice-nightly dosing regimen among people who have switched from the twice-nightly formulation,” Douglas Williamson, MD, chief medical officer, Avadel, said in a statement.2 “Further, they provide an insight into the challenges that patients face with a second, middle-of-the-night dose; challenges which may have been underappreciated due to the lack of other oxybate options. By eliminating the need for a second dose, FT218 has the potential to ease the burden facing sodium oxybate-eligible narcolepsy patients, if approved.”
In June 2021, Roy spoke with NeurologyLive® about data on FT218 that were presented at the 2021 SLEEP Virtual Annual Meeting, June 10-13, from REST-ON. Those data showed that the therapy improved EDS at all dose levels in patients with narcolepsy 1 and 2 as measured by the Maintenance of Wakefulness Test and Clinical Global Impression-Improvement (CGI-I) compared with placebo. Roy and colleagues also confirmed that its effects on patients with and without stimulant use did not change. Both subgroups of patients who received FT218 rated sleepiness as much or very much improved on CGI-I at higher rates than those on placebo. Additionally, the drug had weight-related benefits, significant decreasing patients’ weight and body mass index (BMI) from baseline to week 13.3
“Narcoleptics, unfortunately, often have a lot of metabolic issues. They have an increased risk of cardiovascular disease and increased risk of metabolic issues, and weight is a big player in that. We know that obesity is a big epidemic, so if this therapy has an effect on weight in terms of improving metabolic outcomes—it’s hard to make that leap based on these data alone, but it leans toward improving their sleep might have a positive effect for some of these patients,” Roy said at SLEEP 2021. "Most often—and more often than not—weight reduction or weight stabilization is an important feature and can be a health benefit in most of these patients.”