The FDA has granted approval to Avadel Pharmaceuticals' supplemental new drug application (sNDA) for sodium oxybate (Lumryz) for the treatment of cataplexy and excessive daytime sleepiness (EDS) in pediatric patients aged 7 years and older with narcolepsy. This decision marks a significant advancement in the treatment landscape for this chronic neurological disorder, offering a once-nightly dosing option that aims to improve adherence and quality of life for young patients and their families.
Clinical Significance
Narcolepsy is a debilitating condition affecting approximately 1 in 2,000 individuals in the United States, with about 5% of patients being under 18 years old. Symptoms include EDS, cataplexy (sudden muscle weakness), disrupted nighttime sleep, sleep paralysis, and hallucinations. Current treatment strategies often involve twice-nightly administration of sodium oxybate, which requires patients or caregivers to wake up during the night to take a second dose. This can be disruptive and challenging, leading to poor adherence and reduced treatment effectiveness.
According to Anne Marie Morse, DO, a pediatric neurologist and sleep medicine specialist at Geisinger Health System, the approval of Lumryz provides a valuable alternative. She stated that many families had previously declined or discontinued sodium oxybate treatment due to the difficulties associated with the twice-nightly dosing. The once-nightly formulation offers a more convenient and less disruptive option, potentially improving treatment adherence and outcomes.
Supporting Data
The FDA's approval was supported by data from the Phase 3 REST-ON trial (NCT02720744), a randomized, double-blind, placebo-controlled study in adults with narcolepsy. While the sNDA approval didn't rely on new clinical trials in pediatric patients, the efficacy and safety of sodium oxybate have been established in the adult population, and the drug has been used off-label in children for years. The REST-ON trial demonstrated statistically significant and clinically meaningful improvements in EDS, cataplexy, and overall functioning compared to placebo.
Specifically, the REST-ON trial evaluated doses of 6 g, 7.5 g, and 9 g of once-nightly sodium oxybate. Results showed significant improvements in the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I), and the number of weekly cataplexy attacks across all three doses. For example, patients treated with the 9 g dose showed a 10.82-point change from baseline in MWT score compared to 4.89 for placebo at week 13.
Safety and Warnings
Lumryz carries a boxed warning as a central nervous system depressant and for its potential for abuse and misuse, similar to other sodium oxybate products. It is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Lumryz REMS. Common adverse reactions reported in clinical trials include nausea, dizziness, enuresis (bedwetting), headache, and vomiting. In pediatric trials with immediate-release sodium oxybate, additional adverse reactions included decreased weight, decreased appetite, and sleepwalking.
Market Impact
The approval of Lumryz for pediatric narcolepsy is expected to intensify competition in the narcolepsy treatment market. Jazz Pharmaceuticals' Xyrem and Xywav, both twice-nightly sodium oxybate formulations, are established therapies. However, Lumryz's once-nightly dosing regimen offers a distinct advantage in terms of convenience and adherence. Avadel has been granted orphan drug exclusivity for Lumryz in pediatric narcolepsy until October 2031, providing a period of market protection.
According to GlobalData’s Pharma Intelligence Centre, Lumryz is projected to generate $639 million in revenue by 2030. This expanded indication for pediatric use is likely to contribute to that growth.
Expert Commentary
Greg Divis, CEO of Avadel Pharmaceuticals, emphasized the importance of this approval for younger narcolepsy patients and their caregivers, highlighting the challenges associated with waking up in the middle of the night for treatment. He noted that this label expansion provides pediatric patients with the same option as adults: a once-nightly treatment that does not disrupt sleep.
Anne Marie Morse, DO, also highlighted the positive impact of this approval, stating that she can now offer more options to her patients and their families, allowing her to continue her role as a partner in their journeys.
