Expected to be marketed as Lumryz by Avadel Pharmaceuticals, the extended-release oral suspension sodium oxybate’s final approval is pending the disposition of the REMS patent listed in the FDA’s Orange Book.
The FDA has granted tentative approval to Avadel Pharmaceuticals’ extended-release oral suspension formulation of sodium oxybate, marketed as Lumryz, for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy.1 Previously, the therapy was known as FT218.
The new drug application (NDA) was supported by data from the phase 3 REST-ON study (NCT02720744), which was held under a special protocol assessment agreement with the FDA. Investigators, led by Clete A. Kushida, MD, PhD, director, Stanford Center for Human Sleep Research, randomly assigned 222 patients with narcolepsy type 1 or type 2, all aged 16 years or older, to receive uptitration doses of 4.5 g, 6 g, 7.5 g, and 9 g of FT218 or placebo over the course of a 3-week screening period, a 13-week treatment period, and a 1-week follow-up period. 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.2,3
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).3
“We have reached a critical milestone, as tentative approval confirms the safety profile and clinical efficacy of LUMRYZ for adults with narcolepsy,” Greg Divis, chief executive officer at Avadel Pharmaceuticals, said in a statement.1 “Tentative approval is an important regulatory step forward and indicates LUMRYZ could potentially be granted final approval in 11 months or less. We believe once-at-bedtime LUMRYZ offers the opportunity to positively transform the lives of oxybate-eligible patients living with narcolepsy. Our extensive market research indicates Avadel is well-positioned to capture a significant share of the oxybate-eligible patient population which we estimate to be in excess of 30,000 patients. We are pursuing all options to accelerate final approval on or before June 2023 and prepare for commercial launch.”
The therapy only requires a single nightly dose, which some sleep disorder experts have expressed may offer benefits for patients over the existing therapies for EDS and cataplexy in narcolepsy. Divis told NeurologyLive® that the therapy has the potential to fill an unmet need with this alternative regimen that lacks middle-of-the-night dosing. "Research has shown that people with this chronic neurological disorder strive to restore a natural sleep-wake cycle - and the once-at-bedtime dosing regimen of investigational FT218 could, upon final FDA approval, bring eligible patients one step closer to that. We are dedicated to obtaining final FDA approval of FT218 and therefore making this investigational therapy available to eligible patients as quickly as possible," Divis said.
Additionally, the treatment has also shown weight-related benefits, significant decreasing patients’ weight and body mass index (BMI) from baseline to week 13 in the REST-ON trial. Another of the trial investigators, Asim Roy, MD, medical director, Ohio State Sleep Medicine Institute, sat down with NeurologyLive® previously to discuss the significance of these additive benefits that FT218 brings to patients with narcolepsy in further detail, saying that, "most often—and more often than not—weight reduction or weight stabilization is an important feature and can be a health benefit in most of these patients.”
Earlier this year, in May 2022, Avadel announced that the FDA had issued a proposed final label and medication guide for the therapy, at which time it was also announced that a portion of the NDA for the once-nightly sodium oxybate formulation relating to the REMS patent was deemed inappropriate. The approval deadline was pushed back to June 17, 2023, at that time.4
The finalization of the approval is pending the disposition of the REMS patent (U.S. Patent No. 8,731,963) listed in the agency’s Orange Book, though the FDA noted that this formulation has met all required safety, efficacy, and quality standards for approval. Avadel noted in its announcement that it hopes to potentially accelerate final approval and shorten the time between approval and launch. To do so, it has filed a motion in the US District Court for the District of Delaware to delist the REMS patent from FDA’s Orange Book; is preparing for a claim construction hearing scheduled for August 31, 2022, that the Court previously stated is required for the motion; and is continuing key activities in anticipation of the final approval, such as preparing the REMS program and the continued manufacturing of commercial supply.1