In a significant legal victory for Avadel Pharmaceuticals, the United States Court of Appeals for the Federal Circuit has ruled in favor of the company, overturning critical portions of an injunction that had limited the development of LUMRYZ beyond narcolepsy treatment.
The Federal Circuit vacated the part of the injunction imposed by the U.S. District Court for Delaware that prohibited Avadel from applying for FDA approval of LUMRYZ for indications beyond narcolepsy, describing the district court's analysis as "simply too speculative and tenuous." Additionally, the court lifted restrictions that had prevented Avadel from offering open-label extensions to trial participants and initiating new clinical trials for potential indications beyond narcolepsy.
"We are pleased with the Federal Circuit's decision, which paves the way for Avadel to initiate new clinical trials, offer open-label extensions in clinical trials, and ultimately seek FDA approval of LUMRYZ in IH as well as other indications," stated Greg Divis, Chief Executive Officer of Avadel. "We remain relentlessly committed to demonstrating the clinical value of our differentiated, extended-release, once-at-bedtime medication."
The ruling represents a significant setback for Jazz Pharmaceuticals, which had previously secured the injunction against Avadel's competing sleep disorder treatment.
LUMRYZ Development in Idiopathic Hypersomnia
With this legal barrier removed, Avadel's development program for idiopathic hypersomnia (IH) can proceed unimpeded. The company confirmed that patient enrollment in its REVITALYZ trial remains on track to be completed by the end of 2025.
REVITALYZ is a double-blind, placebo-controlled, randomized withdrawal, multicenter Phase 3 study designed to evaluate the efficacy and safety of LUMRYZ as a once-at-bedtime treatment for IH. The study aims to enroll approximately 150 adults diagnosed with idiopathic hypersomnia and is open to participants switching from immediate-release oxybates as well as those not currently taking oxybates.
LUMRYZ: A First-in-Class Treatment
LUMRYZ (sodium oxybate) for extended-release oral suspension represents a significant innovation in sleep disorder treatment. It was approved by the FDA on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. The FDA expanded this approval on October 16, 2024, to include pediatric patients 7 years of age and older with narcolepsy.
The FDA approval was supported by results from the REST-ON trial, a randomized, double-blind, placebo-controlled Phase 3 study in adults with narcolepsy. LUMRYZ demonstrated statistically significant and clinically meaningful improvements in three co-primary endpoints: excessive daytime sleepiness (measured by MWT), clinicians' overall assessment of patients' functioning (CGI-I), and cataplexy attacks, across all evaluated doses compared to placebo.
The FDA granted 7 years of Orphan Drug Exclusivity to LUMRYZ for the treatment of cataplexy or EDS in both adult and pediatric narcolepsy patients, recognizing its clinical superiority over currently available oxybate treatments. The FDA specifically noted that LUMRYZ makes a major contribution to patient care by providing a once-nightly dosing regimen that eliminates the need for patients to wake during the night to take a second dose.
Clinical Significance and Market Implications
The Federal Circuit's decision has substantial implications for patients with idiopathic hypersomnia, a chronic neurological disorder characterized by excessive daytime sleepiness despite normal or prolonged nighttime sleep. Unlike narcolepsy, IH is not typically associated with cataplexy and has fewer FDA-approved treatment options.
Dr. Richard Bogan, a sleep medicine specialist not affiliated with Avadel, commented on the potential impact: "The development of extended-release oxybate formulations represents a significant advancement for sleep disorder treatments. The once-nightly dosing eliminates middle-of-the-night awakening, which can be particularly beneficial for maintaining sleep architecture."
The ruling also has significant commercial implications. Avadel's ability to pursue indications beyond narcolepsy could substantially expand the potential market for LUMRYZ, challenging Jazz Pharmaceuticals' established position in the oxybate market with its twice-nightly Xyrem and once-nightly Xywav products.
Safety Considerations
As with all medications, LUMRYZ carries important safety considerations. The drug includes a boxed warning regarding its potential for abuse and misuse. Patients taking LUMRYZ should not engage in activities requiring full alertness for at least six hours after taking the medication.
Common side effects in adults include nausea, dizziness, bedwetting, headache, and vomiting, with side effects potentially increasing at higher doses. In children, common side effects include nausea, bedwetting, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking.
Looking Forward
With the legal pathway now cleared, Avadel can accelerate its clinical development program for LUMRYZ in idiopathic hypersomnia and potentially other sleep disorders. The company's focus on once-nightly dosing represents an important advancement in patient care, potentially improving treatment adherence and quality of life for individuals with these challenging neurological conditions.
Industry analysts will be closely watching the progress of the REVITALYZ trial and subsequent regulatory submissions as Avadel works to expand LUMRYZ's approved indications beyond narcolepsy.
