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FDA Approves Avadel's Sodium Oxybate for Cataplexy or Excessive Daytime Sleepiness in Pedatric Narcolepsy
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Key Takeaways
- FDA approved Lumryz for pediatric narcolepsy, offering a once-nightly treatment option, reducing caregiver burden.
- Phase 3 REST-ON trial data supported approval, showing significant improvements in sleep latency.
Sodium oxybate is the only FDA-approved once-at-bedtime treatment for cataplexy or excessive daytime sleepiness in pediatric patients with narcolepsy.
Greg Divis
(Credit: Avadel Pharmaceuticals)
According to a new announcement, the FDA has approved Avadel Pharamaceuticals' supplemental new drug application (sNDA) for sodium oxybate (Lumryz) for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. With this approval, sodium oxybate could reduce the burden on families and caregivers of pediatric patients with narcolepsy who must wake up at night to administer a second dose.1
“This approval represents an important milestone for the narcolepsy community, specifically for younger narcolepsy patients and their caregivers who face significant challenges associated with waking up in the middle of the night to complete treatment regimens. With this label expansion, pediatric patients 7 years and older living with narcolepsy now have the same option that adult patients with narcolepsy have – to choose a once-nightly treatment option that does not disrupt sleep for a middle of the night dose,” Greg Divis, Chief Executive Officer at Avadel Pharmaceuticals, said in a statement.1 “In less than two years, Avadel has made great strides in establishing our commitment to the development of transformative medicines for sleep disorders. This includes successfully launching Lumryz for the adult narcolepsy population, initiating a Phase 3 pivotal trial evaluating Lumryz for the treatment of idiopathic hypersomnia, and now the expansion of Lumryz into the pediatric narcolepsy population.”
In May 2023, the agency initially approved sodium oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy after Avadel submitted an amendment to the FDA’s request for final approval.2 Lumryz comes with a boxed warning as a central nervous system depressant, and for its potential abuse and misuse. It is currently only available through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS. With the approval, the drug was granted 7 years of orphan drug exclusivity.
The initial approval was supported by data from the phase 3 REST-ON trial (NCT02720744). Held under a special protocol assessment agreement with the FDA, the study featured 222 patients with narcolepsy type 1 or 2, all aged 16 years or older, who received uptitration doses of 4.5 g, 6 g, 7.5 g, and 9 g of Lumryz or placebo over the course of a 3-week screening period, 13-week treatment period, and 1-week follow-up period. All told, the study met all 3 of its primary end points of change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression Improvement, and weekly cataplexy attacks within the 6-, 7.5-, and 9-g groups.3
The data from REST-ON showed a significantly greater increase in sleep latency with FT218 treatment at week 3 for the 6-g dose group (8.1 vs 3.1 min, respectively; least-squares mean difference [LSMD], 4.98; 95% CI, 2.90-7.05; P <.001); at week 8 for the 7.5-g dose group (9.6 vs 3.3 min, respectively; LSMD, 6.21; 95% CI, 3.84-8.58; P <.001); and at week 13 for the 9-g dose group compared with placebo (10.8 vs 4.7 min, respectively; LSMD, 6.13; 95% CI, 3.52-8.75; P <.001).
In December 2020, Avadel submitted an NDA for sodium oxybate, formerly known as FT218, along with amendments pursuant to §505(b)(2) and a proposed REMS. More than a year later, in July 2022, the FDA granted tentative approval to the extended-release formulation of sodium oxybate.4 At the time, the finalization of the approval was pending the disposition of the Jazz Pharmaceuticals’ REMS patent (US Patent No. 8,731,963) listed in the agency’s Orange Book, through the FDA noted that this formulation met all required safety, efficacy, and quality standards for approval.
Subsequently, Avadel filed a motion to the US District Court for the District of Delaware to delist the REMS patent from the FDA’s Orange Book, which was approved in a 3-0 unanimous panel decision in February 2023.5 The “963 patent” was related to Jazz’s single-distribution system, which controls access to Xyrem, its twice-nightly, previously approved, formulation of sodium oxybate. Xyrem’s active ingredient is sodium gamma-hydroxybutyrate, commonly known as sodium oxybate, which exerts a heavily sedating effect on patients. GHB is prone to heavy misuse and is infamously known as a date-rape drug.
"I have been prescribing sodium oxybate for children and adolescents with narcolepsy for years as I have seen how effective this medication is and can safely be used," Anne Marie Morse, DO, a board-certified and fellowship-trained pediatric neurologist and sleep medicine specialist at Geisinger Health System, said in a statement.1 “And before this, although numerous families have also witnessed the transformation in their children's lives, I have also had many families turn down the medication, or discontinue after starting, because of the challenge experienced or feared to experience with a forced awakening causing a purposeful nightly disruption, many times met with an exhausting fight, to take the second dose of first-generation oxybates. The expanded FDA approval for Lumryz allows me to now share with my patients and their families that there is an FDA-approved treatment that offers a single bedtime dose of medication, provided in a pre-filled packet. I can now offer more options to more patients which allows me to continue my role as a partner in my patients' journeys."
