Narcolepsy is a rare disorder associated with excessive sleepiness despite adequate sleep time. A potentially highly efficacious therapy for narcolepsy, Xywav, is complicated by a difficult dosing regimen requiring twice nightly administration for optimal effect. A new therapy in development by Avadel may provide a similar benefit in a once nightly dose.
Avadel Pharmaceuticals plc, whose marketing application for narcolepsy drug candidate FT218 is under review by the US Food and Drug Administration (FDA), presented in eight posters at World Sleep 2022. FT218 is 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.
Data presented at World Sleep 2022 include results from a discrete choice experiment designed to characterize and quantify drivers of preferences for attributes associated with oxybate treatments for narcolepsy, with a background survey providing patient and clinician perspectives on narcolepsy disease burden, treatment approaches, and satisfaction with current narcolepsy treatment options. New post-hoc data from the completed pivotal Phase 3 REST-ON clinical trial of FT218 and interim data from the ongoing RESTORE open-label extension/switch study of FT218 was also presented.
“We know that untreated narcolepsy can have a devastating effect on patients’ quality of life and ability to function and that additional treatment options would benefit patients and clinicians. Results from the discrete choice experiment identified that the overall driver of treatment choice for oxybate therapy is once-nightly dosing,” says Anne Marie Morse, DO, director of child neurology and pediatric sleep medicine at Geisinger Medical Center at Janet Weis Children’s Hospital, in a release. “Taken together with the robust clinical data already published, along with new post-hoc analyses from the pivotal trial and interim long-term data from the ongoing open-label study….FT218 shows great potential for patient care.”
Highlights from the Poster Presentations
- The discreet choice experiment confirmed that once-nightly dosing, when compared to twice-nightly dosing, was the most important attribute driving both patient and clinician preference for overall oxybate product choice, as well as patient quality of life and reduction of patient anxiety/stress.
- Dosing frequency was also viewed as a more important attribute as compared to other attributes assessed, including sodium content.
- In the REST-ON post-hoc analyses, FT218 demonstrated improvement in subjective measures of daytime sleepiness, sleep quality, and refreshing nature of sleep as early as week 1 with the 4.5 g starting dose, with even greater improvement at week 2 soon after starting the 6 g dose compared to placebo.
- Additional post-hoc analyses, stratified by narcolepsy type, as well as concomitant stimulant use, or without stimulants, demonstrated positive results that are generally consistent with previously reported positive endpoints from REST-ON and add to the existing body of evidence for FT218.
- In the first presentation of an interim safety analysis from the ongoing RESTORE study, FT218 has generally been well tolerated, with some participants receiving therapy for more than 18 months; no new safety signals have emerged.
“In our first look at data from the interim analysis of the ongoing RESTORE study, we have affirmed that the tolerability of FT218 is in line with the well-established profile of sodium oxybate. We’re also pleased to share new results from our post-hoc analyses of the REST-ON trial that demonstrated clinically meaningful improvements with FT218 versus placebo in both subjective and objective measurements of narcolepsy symptoms, including EDS and disrupted nighttime sleep, with a dosing regimen preferred by patients and clinicians alike, consistent with our previous observations,” says Douglas Williamson, MD, chief medical officer of Avadel, in a release. “At Avadel, we believe in listening to patients to develop solutions that will have a meaningful impact on their symptoms. Our goal is to do just that for people living with narcolepsy, and we are working to bring FT218 to patients as a once-at-bedtime treatment option as quickly as possible.”
