Data presented at SLEEP 2021 also showed the treatment was associated with significant weight loss and reduction in BMI compared to placebo.
Asim Roy, MD
Avadel’s investigational agent FT218 reduced sleep latency across narcolepsy subtypes and produced greater decreases in weight and body mass index (BMI) than placebo, according to new data from the phase 3 REST-ON study (NCT02720744) presented at the 2021 SLEEP Virtual Annual Meeting, June 10-13.1
“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,” said trial investigator Asim Roy, MD, medical director, Ohio Sleep Medicine Institute, in a statement.1
“The new data analyses showing that FT218 improved excessive daytime sleepiness (EDS) 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,” he continued.
FT218 improved EDS at all dose levels in patients with narcolepsy subtype 1 (NT1; with cataplexy; n = 145) and 2 (NT2; without cataplexy; n = 45) in measures such as maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) compared to placebo.2
Patients with NT1 treated with FT218 had a least squares mean (LSM) difference in mean sleep latency (in minutes) on MWT compared to placebo of 5.97 for 9.0 g (week 13), 7.02 for 7.5 g (week 8), and 4.89 for 6.0 g (week 3; all P <.001). Patients with NT2 treated with FT218 had an LSM difference of 6.27 for 9.0 g (P = .020), 4.01 for 7.5 g (P =.162), and 5.33 for 6.0 g (P = .020). A higher proportion of NT1 patients receiving FT218 had significant improvement on CGI-I vs placebo (9.0 g: 75.5% vs 35.9%; 7.5 g: 66.9% vs 27.9%; 6.0 g: 39.9% vs 7.8%; all P <.001).
A post hoc analysis by stimulant use confirmed efficacy in both patients with (63%) and without stimulant use. Patients with stimulant use treated with FT218 had an LSM difference in mean sleep latency on MWT compared to placebo of 5.99 minutes for 9.0 g (week 13), 5.51 minutes for 7.5 g (week 8), and 5.35 minutes for 6.0 g (week 3; all P <.001). Patients without stimulant use treated had a LSM difference of 6.28 minutes for 9.0 g (P = .001), 7.14 minutes for 7.5 g (P <.001), and 4.19 minutes for 6.0 g (P = .007).3
Both subgroups of patients receiving FT218 rated sleepiness as much or very much improved on CGI-I at higher rates than those on placebo (stimulant use: 9.0 g, 80.5% vs 35.3% [odds ratio (OR), 7.55]; 7.5 g, 66.3% vs 26.5% [OR, 5.44]; 6.0 g, 39.8% vs 4.4% [OR, 14.27]; all P <.001; no stimulant use: 9.0 g, 55.1% vs 27.2% [OR, 3.29]; P = .047; 7.5 g, 54.5% vs 17.5% [OR, 5.64]; P = .006; 6.0 g, 40.0% vs 7.7% [OR, 8.04]; P = .003).
Patients treated with FT218 had significantly greater decreases in weight and BMI from baseline to week 13 compared to placebo, with a mean reduction of 1.3 kg (standard deviation [SD], 3.6) from baseline compared to a 0.2 kg weight gain (SD, 2.60) in the placebo group. Overall, 17.8% of patients treated with FT218 lost at least 5% of their weight compared to 3.8% of patients in the placebo group. By week 13, the LSM change in BMI from baseline was ‒0.5 kg/m2 (standard error [SE], 0.13) in the FT218 group and 0.1 kg/m2 (SE, 0.13) in placebo (P = .001).4
“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,” Jennifer Gudeman, PharmD, vice president, medical and clinical affairs, Avadel, added to the statement.1 “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.”
For more coverage of SLEEP 2021, click here.