Lumryz (sodium oxybate extended release) / Avadel - LARVOL DELTA

Extended-release Sodium Oxybate in Children (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Stanford University | Initiation date: Jul 2025 ➔ Oct 2025

Trial initiation date • Narcolepsy • Sleep Disorder

RESTORE: An Open Label Study of FT218 in Subjects With Narcolepsy (clinicaltrials.gov) - P3 | N=184 | Completed | Sponsor: Avadel | Trial completion date: Dec 2023 ➔ Nov 2024

Trial completion date • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder • Sleep Wake Cycle Disorder

Dissolution of Once-Nightly Sodium Oxybate in Soft Foods and Alternative Liquid Reconstitution Vehicles. (PubMed, Clin Ther) - "Lemon pudding, low-fat vanilla yogurt, applesauce, raspberry lemonade solution, fruit punch solution, and alkaline water are viable reconstitution alternatives and maintain the drug dissolution characteristics of ON-SXB when compared to water. Flexibility in the administration of ON-SXB may improve narcolepsy management, enhance medication adherence, and support medication persistency."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Correlation Between Maintenance of Wakefulness Test and Epworth Sleepiness Scale Scores in REST-ON (WSS 2025) - P3 | "After initiating ON-SXB treatment, the correlation between MWT and ESS scores strengthened, suggesting that improved wakefulness enhances awareness of sleepiness levels in people with narcolepsy."

Clinical • Narcolepsy • Sleep Disorder

Safety and Tolerability of Once-Nightly Sodium Oxybate: A Post Hoc Analysis From the Long-Term RESTORE Study (WSS 2025) - P3 | "These data from RESTORE demonstrate that REST-ON and oxybate-naive participants tolerated ON-SXB well, as TEAEs were primarily mild/moderate in severity. ADRs were aligned with the known safety profile of TN-SXB."

Clinical • Retrospective data • Infectious Disease • Mood Disorders • Movement Disorders • Narcolepsy • Novel Coronavirus Disease • Otorhinolaryngology • Psychiatry • Respiratory Diseases • Sinusitis • Sleep Disorder

Improvement of Individual Excessive Daytime Sleepiness Symptoms With Once-Nightly Sodium Oxybate for Narcolepsy (WSS 2025) - P3 | "At all ON-SXB doses, participants had significant improvements vs placebo in sleepiness while completing routine activities. The greatest improvements in these activities were observed with the 9-g ON-SXB dose, including the domain for sleepiness as a driver stopped in traffic, a key safety concern. ON-SXB may be helpful in addressing safety challenges for people with narcolepsy."

Clinical • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Oxybate Awareness, Usage, and Experience Among People With Narcolepsy: A MyNarcolepsyTeam Survey Analysis (WSS 2025) - "Immediate-release twice-nightly sodium oxybate (TN-SXB) and calcium, magnesium, potassium, and sodium oxybates (mixed-salt oxybates) are administered at bedtime and 2.5-4 hours later, whereas extended-release once-nightly SXB (ON-SXB; FT218) is administered once at bedtime... These results demonstrate that while respondents were moderately aware of oxybates, over one-third reported lacking enough information to consider starting oxybate treatment. Despite TN-SXB approval by the FDA in 2002, only 1:8 respondents were currently receiving oxybates. As narcolepsy medication regimens can be daunting, clinicians have the opportunity to counsel PWN about oxybate treatment options, including the potential for early symptom improvement and proactive side effect management to reduce discontinuation."

Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Long-Term Safety and Tolerability of Once-Nightly Sodium Oxybate: A Post Hoc Analysis From RESTORE (WSS 2025) - P3 | "Reported AEs were consistent with the known AEs of oxybates. Only 4% of participants discontinued owing to a TEAE during the stable dosing period, underscoring the largely transient nature of AEs and the long-term tolerability of ON-SXB."

Clinical • Retrospective data • Cardiovascular • Cataplexy • Cough • Fatigue • Gastroenterology • Gastroesophageal Reflux Disease • Hypertension • Infectious Disease • Movement Disorders • Narcolepsy • Nephrology • Novel Coronavirus Disease • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • Sleep Disorder • Urinary Incontinence

Hypnagogic/Hypnopompic Hallucination Types Among Participants With Narcolepsy Type 1 From the Phase 3 REST-ON Trial (WSS 2025) - P3 | "There were low baseline HH rates in REST-ON, and a strong placebo effect was observed. However, these data provide insight into the HH types participants experienced. Relevant to clinician-patient discussions, approximately half the number of events where participants felt like they were about to be attacked, flying through the air, and falling in a hole were reported with ON-SXB vs placebo."

P3 data • Narcolepsy • Sleep Disorder

Consistent Efficacy of Once-Nightly Sodium Oxybate on Disrupted Nighttime Sleep in People With Narcolepsy (WSS 2025) - P3 | "While the trial was not powered to test for subgroup differences, these post hoc analyses demonstrate the robust, consistent efficacy of ON-SXB in treating DNS, including reducing nocturnal arousals and increasing the refreshing nature of sleep, in patients with narcolepsy across various demographic and clinical characteristics."

Clinical • Narcolepsy • Sleep Disorder

Real-World Experience of Once-Nightly Sodium Oxybate Treatment in People With Narcolepsy: Interim Results From REFRESH (WSS 2025) - P | "Participants in REFRESH experienced meaningful symptom improvement with ON-SXB, including improved QOL, reduced drowsy driving, and improved nocturnal sleep. Prior to study entry, switch participants found twice-nightly dosing of TN-OXB burdensome and often missed doses; >90% of switch participants preferred ON-SXB to TN-OXB."

Clinical • Real-world • Real-world evidence • Cataplexy • Excessive Daytime Sleepiness • Fatigue • Narcolepsy • Sleep Disorder

Clinically Meaningful Improvement in Daytime Sleepiness With ON-SXB in People With Narcolepsy and Severe Sleepiness (WSS 2025) - P3 | "The most severely sleepy REST-ON participants at baseline experienced clinically meaningful improvement in daytime sleepiness with ON-SXB treatment, as ESS scores were at or below the normal threshold at the end of the study."

Clinical • Narcolepsy • Sleep Disorder

Successful Transition From Twice-Nightly Oxybates to Once-Nightly Sodium Oxybate: A Post Hoc Analysis From RESTORE (WSS 2025) - P3 | "For participants switching from stable-dose TN-OXB, ON-SXB was well tolerated during the 8-week titration period, with most TEAEs being of mild to moderate severity and consistent with the oxybate safety profile. By week 4, no TEAEs were reported by ≥3% of participants, suggesting resolution of many TEAEs during titration. Participants successfully switched to ON-SXB from their nearest or equivalent prior total nightly TN-OXB dose."

Retrospective data • Cardiovascular • CNS Disorders • Hypertension • Infectious Disease • Insomnia • Movement Disorders • Narcolepsy • Respiratory Diseases • Sleep Disorder • Urinary Incontinence

Assessing Usability of Once-Nightly Sodium Oxybate Extended-Release Oral Suspension for Narcolepsy (WSS 2025) - "Validation to confirm that individuals with narcolepsy can follow labeled instructions for safe use and self-administration of oxybates is important and has been conducted with ON-SXB."

Cataplexy • Excessive Daytime Sleepiness • Excessive Daytime Sleepiness in Narcolepsy • Narcolepsy • Sleep Disorder

Once-Nightly Sodium Oxybate Improves Narcolepsy Symptoms in People With Narcolepsy: Interim Results From the Real-World REFRESH Study (WSS 2025) - P | "After switching from current TN-OXB use to ON-SXB, participants experienced clinically meaningful improvements in ESS scores to within the normal range; narcolepsy disease severity on the NSS improved from moderate at baseline to mild by end of study. Similar results were observed for participants who had prior TN-OXB use or were oxybate-naive. ON-SXB was well tolerated; ADRs were consistent with known oxybate safety profiles."

Clinical • Real-world • Real-world evidence • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder • Urinary Incontinence

Effects of Once-Nightly Sodium Oxybate on Apnea-Hypopnea Index: Post Hoc Analysis From the Phase 3 REST-ON Clinical Trial (WSS 2025) - P3 | "Treatment with ON-SXB was not associated with worsened AHI at any tested dose. ON-SXB was well-tolerated, as the reported respiratory-related ADRs were minimal, and mild or moderate in severity."

Clinical • P3 data • Retrospective data • CNS Disorders • Depression • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Once-Nightly Sodium Oxybate Meets American Academy of Sleep Medicine Criteria for Treatment of Narcolepsy. (PubMed, J Sleep Res) - P3 | "These data demonstrate the robust efficacy of ON-SXB across multiple clinically important narcolepsy symptoms per established CSTs, further supporting the use of ON-SXB in clinical practice. Trial Registration: This manuscript presents the results of a post hoc analysis from the REST-ON clinical trial (NCT02720744)."

Journal • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Extended-release Sodium Oxybate in Children (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2027 ➔ Jul 2027 | Initiation date: Feb 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2027 ➔ Jun 2027

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Narcolepsy • Sleep Disorder

FDA grants orphan drug status to Avadel’s IH treatment (Investing.com) - "Avadel Pharmaceuticals plc...has received Orphan Drug Designation (ODD) from the U.S. Food & Drug Administration (FDA) for its drug LUMRYZ, aimed at treating Idiopathic Hypersomnia (IH), a chronic sleep disorder....LUMRYZ, which is an extended-release sodium oxybate, is currently under evaluation in a Phase 3 trial named REVITALYZ. This double-blind, placebo-controlled study is designed to assess the drug’s efficacy and safety, with an enrollment target of approximately 150 adults diagnosed with IH. The trial is expected to complete enrollment by the end of 2025."

Orphan drug • Trial status • Sleep Disorder

Avadel Pharmaceuticals Announces Favorable Ruling in Appeal of Delaware Court Injunction (Avadel Pharmaceuticals Press Release) - "Avadel Pharmaceuticals plc...announced that the United States Court of Appeals for the Federal Circuit (the 'Federal Circuit') has ruled in favor of Avadel, overturning important parts of the injunction imposed by the U.S. District Court for the District of Delaware (the 'Delaware Court') regarding LUMRYZ as a potential treatment of indications beyond narcolepsy...Additionally, the Federal Circuit lifted the portions of the Delaware Court's injunction that prohibited Avadel from offering open-label extensions to trial participants using LUMRYZ and from initiating new clinical trials or studies with LUMRYZ for potential indications beyond narcolepsy....Patient enrollment in Avadel’s REVITALYZ trial remains on track to be completed by the end of 2025."

Enrollment status • Pipeline update • CNS Disorders

How once-nightly sodium oxybate is processed in the body in healthy volunteers: a plain language summary. (PubMed, J Comp Eff Res) - "The results mean that if people with narcolepsy take the same dose amount of ON-SXB or TN-SXB, their bodies will receive the same amount of SXB in their blood. ON-SXB provides an option for people with narcolepsy to take their medicine once at bedtime without the need for a middle-of-the-night dose, which can improve quality of life."

Journal • Review • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Characterization and treatment patterns of patients treated with immediate-release sodium oxybate for narcolepsy: A propensity score-matched cohort study. (PubMed, J Clin Neurosci) - "No significant differences in comorbidities were observed between cohorts. Although SXB is a highly effective treatment for narcolepsy, this study highlights challenges patients face while taking twice-nightly SXB, which may result in underuse/misuse and suboptimal treatment."

Journal • Cardiovascular • CNS Disorders • Depression • Diabetes • Dyslipidemia • Fatigue • Hypertension • Insomnia • Metabolic Disorders • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Sodium Oxybate: Practical Considerations and Patient Perspectives. (PubMed, CNS Drugs) - "As PWN have varying needs, clinicians should consider a more personalized approach to therapy, including active participation of PWN in their care and shared decision-making between patient and clinician to achieve optimal outcomes. In this review, we discuss the various characteristics and challenges of PWN, present illustrative clinical case scenarios of PWN, provide clinicians with a proposed framework to best address therapy for PWN, and demystify concerns with sodium oxybate."

Journal • Review • CNS Disorders • Narcolepsy • Sleep Disorder

Efficacy of Once-Nightly Sodium Oxybate in Patients with Narcolepsy: Post Hoc Analyses of Sensitivity, Effect Size, and Numbers Needed to Treat from the Phase 3 REST-ON Trial. (PubMed, CNS Drugs) - P3 | "These post hoc results demonstrate the robustness of the REST-ON clinical trial efficacy data."

Journal • P3 data • Retrospective data • Cataplexy • Narcolepsy • Sleep Disorder

Assessing Early Efficacy After Initiation of Once-Nightly Sodium Oxybate (ON-SXB; FT218) in Participants with Narcolepsy Type 1 or 2: A Post Hoc Analysis from the Phase 3 REST-ON Trial. (PubMed, CNS Drugs) - P3 | "ON-SXB improved daytime sleepiness, sleep quality, and refreshing nature of sleep, with observable benefits beginning in the first week of treatment. These data may help clinicians set expectations with patients."

Journal • P3 data • Retrospective data • Narcolepsy • Sleep Disorder