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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
“My initial reaction to the FDA's approval of Lumryz for pediatric use was one of immense pride. We have heard from many parents and caregivers of the challenges they’ve experienced with the twice-nightly dosing required of other oxybates and their interest in a once-nighty treatment option. Lumryz is a testament to our dedication to placing patients at the center of everything we do at Avadel and we’re proud to now serve children with narcolepsy and their families,” Greg Divis, Chief Executive Officer at Avadel Pharmaceuticals, told NeurologyLive®.
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.
"Once-at-bedtime Lumryz addresses the cardinal symptoms of narcolepsy, cataplexy and excessive daytime sleepiness, with a simplified dosing regimen that’s beneficial for both pediatric patients and their families. Differing from twice-nightly oxybates, with Lumryz, children and their families no longer need to awaken from their sleep for a middle-of-the-night medication dose, which can be challenging to adhere to and turn into a disruption for the broader household," Divis said. "As with any medication, Lumryz may not be right for all patients, and we encourage any who are interested in managing their narcolepsy symptoms with treatment to speak with a physician."
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).
Anne Marie Morse, DO, FAASM
(Credit: Society for Womens Health Research)
"When I heard this news today, I have to say that it only delighted me in such an incredible capacity because of the fact that this is necessary for us to be able to continue to better treat our children and adolescents who have narcolepsy. Specifically, I would say that this really resonated very strongly for me because an approval of an oxybate is what led to me developing my interest in focus within narcolepsy when I was a fellow. This was when there was the initial studies done with a twice nightly sodium oxybate in pediatrics, which led to the initial approval for use of oxybates in children," Anne Marie Morse, DO, FAASM, the director of Child Neurology and Pediatric Sleep Medicine at Geisinger Janet Weis Children's Hospital as well as the program director for Child Neurology Residency Program, told NeurologyLive.
"Since that time, we still continue to have a limited landscape. We most recently saw a new alerting agent with pitolisant getting a pediatric approval for excessive daytime sleepiness, but now having a once nightly sodium oxybate being available only allows me to treat more patients more effectively," Morse, who also is the host of the Sleeping Around the Podcast × NeurologyLive, added. "This really has been just a monumental day because we're now continuing to move the needle to really treat every patient, not just some."
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.
"What I think is fabulous around the consideration of now having a once nightly sodium oxybate available for treatment in pediatrics is that although the once nightly sodium oxybate is the newest formulation available, we have over 20 years experience of utilizing oxybate medications in various forms for the treatment of this condition," Morse said. "Therefore, we also have tremendous experience in regards to Its safety profile and generally, what we see as dose related adverse effects. Most commonly, we're going to encounter adverse effects when we first start the medication because your body is undergoing a shock. It is a new medication that you're experiencing, and your body is giving a response to it."
