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Findings from a post-hoc analysis of the pivotal Phase III REST-ON trial (NCT02720744) show that patients with narcolepsy administered Lumryz (sodium oxybate) experienced the added benefit of decreased body mass index (BMI) and weight across the 13-week trial.1-3 The extended-release sodium oxybate medication was granted FDA approval on May 1, 2023. Lumryz was the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness (EDS) indicated for adults with narcolepsy.
“Obesity is a struggle for many people, and it is very common in patients with narcolepsy,” study co-author Asim Roy, MD, co- medical director of the Ohio Sleep Medicine Institute, said in a press release. “Obesity is an important modifiable risk factor for cardiovascular diseases. These new data show that Lumryz use was associated with a reduction in body mass index and weight during the 13-week trial. While all REST-ON participants, including both narcolepsy type 1 (NT1) (with cataplexy) and narcolepsy type 2 (NT2) (without cataplexy) showed improvement in core narcolepsy symptoms (i.e., excessive daytime sleepiness and cataplexy), this improvement was even more pronounced in the subgroup experiencing a ≥5% weight loss.”3
One in 2000 individuals in the United States is affected by narcolepsy. EDS is the primary symptom that characterizes the condition, with 70% of patients also experiencing cataplexy—a sudden weakening of muscles.4
The post-hoc analysis of the double-blind, placebo-controlled, multicenter, randomized REST-ON trial included 222 patients who were randomly assigned to receive Lumryz or placebo. A total of 212 patients were administered at least one dose Lumryz or placebo (Lumryz, n = 107 [NT1, n = 80]; placebo, n = 105 [NT1, n = 82]), with 148 (69.8%) patients completing the trial (Lumryz, n = 69 [64.5%]; placebo, n = 79 [75.2%]). Investigators recorded weight and BMI at baseline and at the end of the study. Among trial participants, the mean age was 31.2 years, 67.9% of participants were women and 75.5% of participants were white.
Among patients administered Lumryz (n=107), 67.5% of those with narcolepsy type 1 (NT1) and 37.0% of those with narcolepsy type 2 (NT2), were overweight or obese at baseline, compared with 69.5% and 61.0%, respectively, in the placebo cohort (n=105). Mean weight at baseline was 81.2 kg in the Lumryz cohort and 82.1 kg in the placebo cohort.
At week 13 of the trial, mean weight dropped by 1.3 (3.6) kg in the Lumryz cohort and increased 0.2 (2.6) kg in the placebo cohort. Further, 17.8% (19/107; NT1, n = 14; NT2, n = 5) of patients in the Lumryz cohort achieved ≥5% weight loss compared with 3.8% in the placebo (4/105; NT1, n = 3; NT2, n = 1; P = 0.001) cohort.
After 13 weeks, least squares mean BMI change from baseline was ‒0.51 (0.13) kg/m2 in the Lumryz cohort compared with 0.08 (0.13) kg/m2 in the placebo cohort (least squares mean difference [95% CI], −0.59 [−0.95 to −0.23] kg/m2; P = 0.001). Investigators observed improved EDS in both Lumryz groups, with the ≥5% weight-loss subgroup showing a larger improvement in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale compared with the other subgroup (weight loss <5%, no change, or weight gain) (Maintenance of Wakefulness Test, P = 0.019; Epworth Sleepiness Scale score, P < 0.001).
“Narcolepsy is often associated with obesity, which may increase cardiometabolic risks,” the study authors wrote. “[Lumryz], an effective treatment for excessive daytime sleepiness and cataplexy, may be preferred in overweight or obese individuals to provide a more tailored treatment approach.”1
In terms of safety, there was a higher rate of nausea and vomiting among patients in the weight-loss group, but a lower rate of study discontinuation than rates in both the Lumryz and placebo cohorts.
“Given the high rates of obesity in the US, and its associated cardiometabolic risks, we were encouraged to see that nearly one in five study participants treated with Lumryz experienced clinically meaningful weight loss,” said Jennifer Gudeman, PharmD, senior vice president, Medical and Clinical Affairs of Avadel, in the release. “These findings suggest that Lumryz, given its proven benefit in reducing cataplexy and EDS, as well its once-at-bedtime dosing, which provides the opportunity for an uninterrupted night sleep, has the potential to provide a more tailored treatment approach for people with narcolepsy who are overweight or living with obesity.”3
References
1. Roth T, et al. Weight Loss With Once-nightly Sodium Oxybate for the Treatment of Narcolepsy: Analysis From the Phase III Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) Trial, Clinical Therapeutics, 2024, ISSN 0149-2918, https://doi.org/10.1016/j.clinthera.2024.07.010.
2. Once-Nightly Sodium Oxybate for Treatment of Excessive Daytime Sleepiness and Cataplexy in Narcolepsy. ClinicalTrials.gov. March 22, 2022. Accessed August 21, 2024. https://clinicaltrials.gov/study/NCT02720744
3. Avadel Pharmaceuticals Announces Publication in Clinical Therapeutics of Data Highlighting Weight Loss in People with Narcolepsy Treated with LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension. News release. Avadel Pharmaceuticals. August 20, 2024. Accessed August 21, 2024.
4. About Narcolepsy. Xyrem. Accessed August 21, 2024. https://www.xyrem.com/narcolepsy-cataplexy-eds-xyrem-information#:~:text=Excessive%20Daytime%20Sleepiness%20(EDS),-Everyone%20with%20narcolepsy&text=People%20with%20narcolepsy%20may%20take,feel%20more%20than%20just%20sleepy