0603 Characterization of Patients Who Had ≥5% Weight Loss With FT218 (Once-Nightly Sodium Oxybate): Post Hoc Analysis From REST-ON Free

Narcolepsy, particularly type 1 (NT1), is often comorbid with obesity. FT218 (LUMRYZ™) is an investigational once-nightly sodium oxybate (ON-SXB) formulation whose efficacy and safety were shown in the phase 3 REST-ON clinical trial (NCT02720744).

REST-ON was a 13-week, randomized (1:1), double-blind, placebo-controlled multicenter study in patients ≥16 years old with NT1/NT2. Stable concomitant stimulant use was permitted. A post hoc analysis of participants in the ON-SXB group experiencing ≥5% weight loss (weight-loss group) was conducted.

In REST-ON (n=212), mean participant age was 31.2 years (range, 16–72), 67.9% were female, 75.5% were white, 76.4% had NT1, mean baseline BMI was 28.1 kg/m2 (range, 16.9–71.9), and 61.3% were taking stimulants. At week 13, 17.8% (19/107) of participants receiving ON-SXB experienced ≥5% weight loss vs 3.8% (4/105) of participants receiving placebo (P< 0.001). Compared to the REST-ON population, the weight-loss group had similar age and proportion of NT1 diagnosis, a smaller proportion was female, and a higher proportion was white and was taking stimulants. At baseline, mean BMI was 25.6 kg/m2 (range, 20.3–34.0) in the weight-loss group, 47.4% (9/19) were overweight (BMI 25.0–29.9 kg/m2) or obese (BMI >30 kg/m2); none were underweight (BMI < 18.5 kg/m2). At week 13, 31.6% (6/19) remained overweight or obese; none were underweight. Excessive daytime sleepiness was significantly improved from baseline to week 13 (ON-SXB 9 g) in the weight-loss group vs the ON-SXB group without weight loss (Maintenance of Wakefulness test, P< 0.05; Epworth Sleepiness Scale score, P< 0.001). Adverse events of nausea and vomiting were more frequent in the weight-loss group vs the ON-SXB group without weight loss; however, rate of discontinuations owing to AEs in the weight-loss group was approximately half that of the ON-SXB group without weight loss.

These data expand the body of knowledge regarding weight loss during treatment with sodium oxybate. Given the high proportion of comorbid obesity among people with narcolepsy, the additional benefit of potential weight loss with sodium oxybate may further inform treatment selection. Whereas ON-SXB was effective overall, further exploration of possible increased pharmacologic response in certain subgroups should be evaluated.

Avadel Pharmaceuticals