Avadel Pharmaceuticals presented compelling new data on LUMRYZ (sodium oxybate) for extended-release oral suspension at World Sleep 2025 in Singapore, reinforcing the therapeutic benefits of the first and only once-nightly oxybate treatment for narcolepsy. The company showcased 17 abstracts, including one oral presentation, with particular emphasis on real-world evidence from the REFRESH study demonstrating meaningful symptom improvements in patients with narcolepsy.
REFRESH Study Delivers Real-World Evidence
The REFRESH study, a prospective multicenter real-world study involving 51 patients with narcolepsy, provided updated interim results showing clinically meaningful improvements across multiple measures. Participants experienced significant improvements in Epworth Sleepiness Scale (ESS) scores, a key measure of excessive daytime sleepiness (EDS), with scores improving to within the normal range.
"The emerging data from the REFRESH study provide further evidence of symptom improvement with LUMRYZ," said Jennifer Gudeman, Pharm.D., Senior Vice President, Medical and Clinical Affairs of Avadel. "While the magnitude of change was greatest for those not on an oxybate at study entry, meaningful improvements were also observed in the twice-nightly oxybate switch cohort showing additional clinical benefit that can be gained by consistently taking a single, full therapeutic dose of oxybate at bedtime."
The study demonstrated that participants experienced a reduction in severity from moderate at the start of the study to mild at study end for the pentad of narcolepsy symptoms measured on the Narcolepsy Severity Scale (NSS). Additionally, patients showed reduced interference across domains on the Sheehan Disability Scale (SDS).
Patient-Reported Outcomes Show Broad Improvements
After completing four months of therapy, the REFRESH study revealed impressive patient-reported outcomes. Among switch participants (n=20), 70% and 76% showed improvement on the Patient Global Impression of Change and the Clinician Global Impression of Change, respectively. For non-switch participants (n=31), these figures were even higher at 90% and 87%.
Additional interim results from study questionnaires and end-of-study surveys showed that overall quality of life, fatigue, brain fog, depression, anxiety, and mood improved. Notably, as-needed use of stimulants was also reduced among participants.
Clinical Advantages of Once-Nightly Dosing
The presentations highlighted the practical benefits of LUMRYZ's novel once-nightly delivery system. "LUMRYZ's novel once-nightly delivery system means patients do not have to worry about not waking up and missing their second dose," explained Gerard J. Meskill, MD, CEO of Tricoastal Narcolepsy and Sleep Disorders Center. "The single bedtime dose helps assure patients receive the full therapeutic benefit of their medication every night, demonstrated in the REFRESH study to result in clinically meaningful outcomes for both switch and naïve oxybate patients."
Dr. Meskill also emphasized the broader impact on patients' lives: "It also means their partners don't have to wake up to an alarm, which is a forgotten burden of this disease and can be a source of guilt for patients."
Comprehensive Comorbidity Analysis
A significant component of the World Sleep 2025 presentations included new research on narcolepsy comorbidities. An analysis of aggregate patient data from electronic health records conducted at Duke University examined 1,659 patients with narcolepsy and 1,659 matched controls. The results revealed that sleep, pain, and psychiatric or mood disorders occurred significantly more frequently in patients with narcolepsy versus the control group (all p<0.0001). Notably, hypertension and cardiovascular disease were not included in the top 23 comorbidities identified to be increased.
Regulatory Status and Clinical Foundation
LUMRYZ received FDA approval on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness in adults with narcolepsy. The approval was extended on October 16, 2024, to include pediatric patients seven years of age and older with narcolepsy.
The FDA approval was supported by results from REST-ON, a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial in adults with narcolepsy. LUMRYZ demonstrated statistically significant and clinically meaningful improvements in the three co-primary endpoints: EDS (MWT), clinicians' overall assessment of patients' functioning (CGI-I), and cataplexy attacks, for all three evaluated doses when compared to placebo.
The FDA granted seven years of Orphan Drug Exclusivity to LUMRYZ due to a finding of clinical superiority relative to currently available oxybate treatments. The FDA specifically recognized that LUMRYZ makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose.
Safety Profile and Considerations
LUMRYZ carries important safety considerations, including a boxed warning regarding the risks of taking the medication with other central nervous system depressants. The most common side effects in adults include nausea, dizziness, bedwetting, headache, and vomiting, while children may also experience decreased weight, decreased appetite, and sleepwalking.
The medication is available only through certified pharmacies in the LUMRYZ REMS program, reflecting its controlled substance status as a form of gamma hydroxybutyrate (GHB). Patients must be enrolled in the LUMRYZ REMS to receive the medication, and healthcare providers must follow specific prescribing and monitoring protocols.
