The final approval was based on efficacy and safety data from the phase 3 REST-ON study.
FDA has granted final approval to an extended-release formulation of sodium oxybate (Lumryz, Avadel Pharmaceuticals) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. With this final approval, sodium oxybate is the first and only FDA approved oxybate to be given once before bedtime for patients with narcolepsy. Additionally, the FDA also granted sodium oxybate Orphan Drug Exclusivity.
“Previously approved narcolepsy therapies have the potential to disrupt sleep by either causing insomnia or through forced awakening during the middle of the night for their crucial second dose. [Sodium oxybate] can now offer people with narcolepsy the opportunity for an uninterrupted night sleep while receiving the full benefit of their prescribed treatment in one single bedtime dose that addresses their symptoms of narcolepsy,” said Greg Divis, chief executive officer of Avadel, in a press release.
A chronic neurological condition, narcolepsy impairs the brain's ability to regulate a sleep-wake cycle and affects approximately one in 2000 people in the United States. With a cardinal symptom of EDS, narcolepsy can have additional symptoms, such as disrupted nighttime sleep, a sudden loss of muscle tone triggered by strong emotion (cataplexy), sleep paralysis, and hallucinations.
“This long-awaited therapy for people living with narcolepsy fills a critical unmet need by avoiding the burden of a second middle-of-the-night dose that immediate-release oxybate products require. The once-at-bedtime dosing regimen of [sodium oxybate] may help restore a more natural sleep-wake cycle,” said REST-ON study investigator Michael J. Thorpy, MD, director at the Sleep-Wake Disorders Center at Montefiore Medical Center and professor of neurology at the Albert Einstein College of Medicine.
The final approval of sodium oxybate was based on the results of the phase 3 REST-ON clinical study (NCT02720744) completed in March 2020. The trial demonstrated highly statistically significant (p<0.001) and clinically meaningful improvement compared to placebo across all 3 co-primary endpoints (Maintenance of Wakefulness Test, Clinical Global Impression-Improvement and mean weekly cataplexy attacks) for all 3 doses evaluated: 6 grams, 7.5 grams, and 9 grams.
The FDA noted that they also found sodium oxybate to be clinically superior to the currently marketed twice-nightly oxybate products, leading the agency to grant the drug Orphan Drug Exclusivity for 7 years. Additionally, FDA explained that treatment with sodium oxybate provides a significant contribution to patient care and quality of life over the current twice-nightly oxybate products.
Orphan Drug Exclusivity is allotted under the FDA's Orphan Drug program, which is designed to support drug development for conditions affecting less than 200,000 patients in the United States. Further, 7-year Orphan Drug Exclusivity gives sodium oxybate market exclusivity for 7 years starting on the date of the approval, which is May 1, 2023.
“For people living with narcolepsy, and for all of us who advocate for this community, the approval of [sodium oxybate] is an important step forward,” Julie Flygare, JD, president and CEO of Project Sleep, said in a press release. “People living with narcolepsy will finally have a new treatment option to manage EDS and cataplexy, and the fact that this new oxybate option allows for reduced dosing frequency is a game-changing advancement that shows Avadel’s commitment to understanding the patient experience.”
Notably, sodium oxybate is a central nervous system depressant with a boxed warning and has the potential for abuse and misuse. For this reason, sodium oxybate is available only through the LUMRYZ Risk Evaluation and Mitigation Strategy (REMS), which establishes restricted access under the REMS program. Most common adverse events (incidence > 5% and greater than placebo) for all doses of sodium oxybate included nausea, dizziness, enuresis, headache, and vomiting.
“We would like to thank the patients, caregivers, clinical trial investigators, healthcare providers, and advocates who have tirelessly partnered with us throughout the drug development process and look forward to providing the narcolepsy community access to now approved [sodium oxybate],” Greg Divis, chief executive officer of Avadel, said in a press release.
Avadel Pharmaceuticals Announces Final FDA Approval of LUMRYZ™ (sodium oxybate) for Extended-Release Oral Suspension as the First and Only Once-at-Bedtime Oxybate for Cataplexy or Excessive Daytime Sleepiness in Adults with Narcolepsy. Dublin, Ireland: Avadel Pharmaceuticals; May 1, 2023. Accessed May 1, 2023. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-final-fda-approval-lumryztm