Once-Nightly Narcolepsy Drug Preferred by Patients Over Twice-Nightly Dose

INDIANAPOLIS -- Extended-release sodium oxybate (Lumryz) taken once before bedtime was preferred by patients with narcolepsy over twice-nightly dosing and was generally well tolerated, according to interim data from the ongoing open-label RESTORE trial presented here.

Among 130 patients who had switched from twice-nightly dosing with immediate-release sodium oxybate to extended-release dosing, 94% preferred once-nightly dosing, reported John Harsh, PhD, clinical research director at the Colorado Sleep Institute, during the annual SLEEP meeting, hosted jointly by the American Academy of Sleep Medicine and the Sleep Research Society.

Harsh noted that immediate-release sodium oxybate has been the standard-of-care treatment for narcolepsy since the mid-2000s. After a first dose at bedtime, patients must take a second dose of the drug 2.5 to 4 hours later.

Prior to switching, 65% of patients reported having missed the second dose of immediate-release sodium oxybate within the previous 3 months, and 80% of these patients reported feeling worse the next day.

Of the 60% of patients who reported taking a second dose of the immediate-release drug more than 4 hours after taking their first dose, 51% said they felt "somewhat," "quite a bit," or "extremely" groggy or unsteady the day after.

Overall, 71% of patients who had taken immediate-release sodium oxybate reported they found taking the second nightly dose to be "somewhat," "quite a bit," or "extremely" inconvenient.

Other problems related to the second dose of immediate-release sodium oxybate were anxiety (29.2%) and the need to be awakened by someone else (23.1%). In the previous 3 months, 90.8% of patients got out of bed after waking to take the second dose, and nine reported having fallen, with five reporting injuries.

In the phase III REST-ON study, once-nightly extended-release sodium oxybate was found to improve narcolepsy symptoms, with a safety profile that was consistent with immediate-release sodium oxybate.

The extended-release formulation of sodium oxybate was approved last month by the FDA for cataplexy and excessive daytime sleepiness in adults with narcolepsy. The RESTORE trial was designed to assess the long-term safety and tolerability of the extended-release dose, as well as patient preferences for once-nightly or twice-nightly dosing.

At the interim data analysis, preference questionnaires and nocturnal adverse event questionnaires were analyzed.

The most commonly reported adverse events were nausea (13.3%), somnolence (7.8%), enuresis (6.7%), and headache (6.7%). Fourteen participants experienced a severe adverse event, and 12 patients discontinued the drug due to adverse events.

Also at the SLEEP meeting, Melissa Lipford, MD, of the Mayo Clinic in Rochester, Minnesota, reported data from a propensity score-matched cohort study assessing the characteristics of narcolepsy patients who did and did not take sodium oxybate within the Mayo Clinic health system.

"Use of sodium oxybate has been endorsed by the American Academy of Sleep Medicine in its practice parameters for the treatment of daytime sleepiness, cataplexy, and disruptive sleep in narcolepsy patients since 2007, with that recommendation elevated to 'strong' in 2021," Lipford said.

Despite this, the Mayo Clinic study is among the first to explore the drug's use in a real-world setting.

The researchers used aggregated electronic health record data to identify patients with narcolepsy, and included 351 who were treated with the drug at some point during their care. They were matched by age and sex to 351 patients who were not treated with sodium oxybate.

The analysis revealed no significant differences in comorbidities, including cardiovascular disorders, obstructive sleep apnea, and mood disorders, between patients who took the drug and those who did not.

About 73% of patients treated with sodium oxybate had a diagnosis of narcolepsy with cataplexy, while just 27% of patients with narcolepsy without cataplexy took the drug.

"We know that when we are thinking about treating patients with sodium oxybate, one potential contraindication might be hypertension or other cardiovascular comorbidities, given the sodium content," Lipford said. "But when we looked at the cardiovascular comorbidities, there actually weren't significant differences between the treated patients and the control group."

Lipford concluded that despite the American Academy of Sleep Medicine practice parameters and studies showing the drug to be effective for the treatment of narcolepsy symptoms, the analysis showed that fewer than one in 10 patients in their cohort took the drug.

"I think we need to do more work to understand why the majority of patients in our cohort did not take sodium oxybate," she added. "One of the things we need to look at is the use of potentially contraindicated medications such as opiates, benzodiazepines, or potentially alcohol. But I also think we need to look at provider-related issues, particularly ascertainment of perceived risk and administrative burden."