Avadel Pharmaceuticals plc, a company focused on developing FT218, an investigational, once-nightly formulation of sodium oxybate for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy, releases at SLEEP 2021 new post hoc analyses of data from the completed pivotal Phase 3 REST-ON clinical trial of FT218.
FT218 is currently under review at the US Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target date of October 15, 2021.
“For the past 20 years, the standard of care for narcolepsy has been a twice-nightly medication, a challenging dosing regimen that disrupts nighttime sleep. The new data from the REST-ON trial demonstrate that the once-nightly formulation of sodium oxybate taken at bedtime was effective in addressing the symptoms of narcolepsy without requiring the patient to wake up in the middle of the night,” says Asim Roy, MD, trial investigator and medical director of the Ohio Sleep Medicine Institute, in a release. “The new data analyses showing that FT218 improved excessive daytime sleepiness in patients with narcolepsy, both with and without cataplexy, regardless of stimulant use, are important for this patient population. Moreover, the data demonstrating a reduction in weight is an added benefit for narcolepsy patients, who tend to be overweight. I am encouraged by these and other data and believe FT218, if FDA approved, will be an important once-nightly treatment option for people who struggle with managing narcolepsy.”
Highlights from the poster presentations are outlined below.
- FT218 demonstrated statistically significant improvement in excessive daytime sleepiness (EDS) at all evaluated doses in patients with narcolepsy subtypes 1 (NT1, with cataplexy) and 2 (NT2, without cataplexy), with greater improvement in measures of EDS, including mean sleep latency on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in overall condition, compared to placebo.
- The least squares (LS) mean difference in mean sleep latency (in minutes) on MWT between FT218 and placebo was 6.0 for 9 g (week 13), 7.0 for 7.5 g (week 8), and 4.9 for 6 g (week 3) in NT1 patients (all p<0.001), and 6.3 for 9 g (P<0.05), 4.0 for 7.5 g (P=NS), and 5.3 for 6 g (P<0.05) in NT2 patients.
- A significantly greater percentage of patients with NT1 receiving FT218 were rated as much or very much improved on the CGI-I compared to placebo: 75.5% vs. 35.9% at 9 g, 66.9% vs. 27.9% at 7.5 g, and 39.9% vs. 7.8% at 6 g (all P<0.001). A greater percentage of NT2 patients receiving FT218 were rated as much/very much improved at all three doses vs. placebo.
- FT218 demonstrated statistically significant improvement in EDS at all evaluated doses in narcolepsy patients with or without stimulant use, with improvement over placebo on MWT and CGI-I.
- The LS mean difference in mean sleep latency (in minutes) on MWT between FT218 and placebo was 6.0 for 9 g (week 13), 5.5 for 7.5 g (week 8), and 5.4 for 6 g (week 3) for patients with concomitant stimulant use (all P≤0.001). For patients not taking stimulants, the LS mean difference was 6.3 for 9 g (P=0.001), 7.1 for 7.5 g (P<0.001), and 4.2 for 6 g (P<0.01).
- More patients receiving FT218 were rated much/very much improved on CGI-I compared to placebo: 80.5% vs. 35.3% at 9 g, 66.3% vs. 26.5% at 7.5 g, and 39.8% vs. 4.4% at 6 g for patients with stimulant use (all P<0.001); 55.1% vs. 27.2% at 9 g (P<0.05), 54.5% vs. 17.5% at 7.5 g (P=0.006), and 40.0% vs. 7.7% at 6 g (P<0.01) for patients without stimulant use.
- Patients receiving FT218 experienced a significantly greater decrease in weight and body mass index (BMI) from baseline to study end (week 13) compared to placebo.
- At study end, the mean (SD) change in weight from baseline was –1.3 (3.6) kg for patients receiving FT218 compared to 0.2 (2.6) kg for patients receiving placebo. Overall, 17.8% of patients receiving FT218 compared to 3.8% of patients receiving placebo experienced ≥5% weight loss.
- At study end, the LS mean (SE) change in BMI from baseline was ‒0.5 (0.13) kg/m2 for patients receiving FT218 and 0.1 (0.13) kg/m2 for patients receiving placebo (P=0.001).
“Avadel is focused on providing a meaningful solution for people with narcolepsy and we are pleased to share further evidence of the clinical benefit of FT218, taken once at bedtime,” says Jennifer Gudeman, PharmD, vice president of medical and clinical affairs at Avadel, in a release. “We leveraged our unique scientific capabilities to develop a proprietary formulation of sodium oxybate to address the limitations of currently available treatments that require twice-nightly dosing. We believe these new analyses, along with previously presented REST-ON positive Phase 3 data, strengthen the body of evidence demonstrating that FT218, if approved, has the potential to be a transformative treatment for people living with narcolepsy.”
Previously released results from the REST-ON trial demonstrated highly statistically significant (p<0.001 compared to placebo) and clinically meaningful improvement across all three co-primary endpoints (MWT, CGI-I, and mean weekly cataplexy attacks) with FT218 at 6, 7.5 and 9 g. Secondary endpoint data for FT218 taken once at bedtime demonstrated clinically meaningful results at all tested doses, for reducing disturbed nocturnal sleep; additional post hoc analyses further demonstrated significant increase in time in deep sleep, and significant decrease in light sleep compared to placebo for doses evaluated beginning by week 3 with only a 6-g-dose. As reported at the American Academy of Neurology 2021 meeting, FT218 also demonstrated a significant improvement in the Epworth Sleepiness Scale, a patient reported outcome, and significantly improved patient perceptions of the quality and refreshing nature of sleep at all doses tested beginning by week 3. FT218 taken once at bedtime at 9 g was generally well tolerated with commonly known sodium oxybate adverse reactions occurring at low rates. These findings will also be presented by Avadel at SLEEP 2021 in an oral and poster session (abstract # 488) and two additional posters (abstract # 489 and 490).
The company is also hosting a virtual medical booth that houses the posters, an on-demand symposium titled “How Narcolepsy Management Is Evolving: Expert Panel Discussion,” and detailed information about its ongoing research and publications. The virtual medical booth can be accessed at http://www.sleep2021.avadelmedicalbooth.com/ until November 30, 2021.