Avadel Pharmaceuticals plc, a company focused on developing FT218, an investigational, once-nightly formulation of sodium oxybate (ON-SXB) for the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy, presented positive secondary endpoint data at the 2021 American Academy of Neurology Annual (AAN) Meeting being held virtually from April 17-22, 2021. FT218 is currently under review at the US Food and Drug Administration with a Prescription Drug User Fee Act (PDUFA) target date of October 15, 2021.
“The positive results previously disclosed from the REST-ON trial, regarding the three co-primary endpoints, are further bolstered by the secondary endpoints presented at AAN. The consistency with which FT218, or once-nightly sodium oxybate, improved both subjective and objective symptoms of narcolepsy—including disturbed nocturnal sleep—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 three weeks, with only a 6 g dose,” says Michael J. Thorpy, MD, investigator on the REST-ON Phase 3 trial and Director at the Sleep-Wake Disorders Center at Montefiore Medical Center and Professor of Neurology at the Albert Einstein College of Medicine, in a release. “I know that clinicians have been eager to learn more about a once-nightly form of sodium oxybate, and we appreciate this forum to present these data.”
Jennifer Gudeman, PharmD, vice president of Medical and Clinical Affairs at Avadel, says in a release, “FT218 demonstrated significant (P<0.001) and clinically meaningful results versus placebo at all doses tested for secondary endpoints of the Epworth Sleepiness Scale, sleep quality and refreshing nature of sleep, sleep paralysis, and disturbed nocturnal sleep, representing an improvement on important narcolepsy symptoms. We are pleased that neurologists attending AAN will have the opportunity to learn about a once-nightly form of sodium oxybate. We believe that patient perspective is critical to successful long-term therapy, and we are presenting several positive endpoints supporting symptomatic improvement as determined directly by patients.”
Data highlights from the poster presentations are outlined below:
- FT218 demonstrated significant consolidation of sleep on polysomnography (randomized, n=212) for the 6 g dose at Week 3, the 7.5 g dose at Week 8, and 9 g dose at Week 13 compared to placebo
- Data from the randomized, double-blind, placebo-controlled, multicenter, parallel-group study showed that the mean difference between FT218 and placebo for disturbed nocturnal sleep (shifts from deeper to lighter stages of sleep and wake) was statistically significant (P<0.001) at all doses tested: –22.63 at 9 g (week 13), –17.70 at 7.5 g (week 8), and –11.00 at 6 g (week 3).
- The mean difference between FT218 and placebo for number of arousals was –23.68 (P<0.001) at 9 g, –19.41 (P<0.001) at 7.5 g and –11.29 (P<0.021) at 6 g.
- FT218 was generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.
Daytime Sleepiness, Sleep Quality, Hallucinations, and Sleep Paralysis in Patients with Narcolepsy: Results From the REST-ON Trial, a Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation
- FT218 demonstrated significant (P<0.001) improvement in the Epworth Sleepiness Scale (ESS) versus placebo at all doses tested: LS mean difference –3.86 at 9 g (week 13), –3.16 at 7.5 g (week 8), and –2.06 at 6 g (week 3).
- FT218 showed a statistically significant (P<0.001) improvement compared to placebo at all doses tested for sleep quality and refreshing nature of sleep on a visual analogue scale, and for sleep paralysis on a sleep symptom diary (P=0.037, 0.021, 0.039 at 9, 7.5, 6 g, respectively).
- FT218 did not demonstrate significant improvement for hypnagogic compared to placebo.
- Adverse events were similar to the known sodium oxybate safety profile.