New data show effectiveness of approved narcolepsy drug Xywav
Oral therapy improved sleep quality, reduced daytime sleepiness in trial
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The approved narcolepsy drug Xywav is designed to improve patient sleep. (Photo from iStock)
Xywav (calcium, magnesium, potassium, and sodium oxybates), an approved medication for narcolepsy, is effective in easing disease symptoms, working to both reduce excessive daytime sleepiness and improve nighttime sleep quality in people with the rare sleep-related disorder.
That’s according to newly published results from the Phase 4 DUET clinical trial (NCT05875974), completed in 2025, which evaluated changes in sleep assessment tests among people with narcolepsy “after taking the best dosage of [Xywav].” The data showed that study participants experienced improvements in both sleep architecture, a pattern of sleep stages measured during a sleep study, and subjective self-assessments of symptoms.
Per the researchers, these findings extend prior trial results to people with both types of narcolepsy, and also expand on the effects of Xywav on nighttime sleep.
“Improvement in sleep architecture and sleep quality with [Xywav] treatment is an important and consequential finding,” the team wrote.
The study, “Effectiveness and Safety of Low-Sodium Oxybate in Participants with Narcolepsy: Primary Results from the DUET Study,” was published in the journal Neurology and Therapy. Jazz Pharmaceuticals, the developer of Xywav, sponsored the trial and employs most of the study’s authors.
In narcolepsy, normal cycles of sleeping and waking become dysregulated. This leads to excessive sleepiness during the day, as well as disruption of sleep at night. The condition can affect both rapid eye movement (REM) and non-REM stages of sleep.
There are two forms of narcolepsy: type 1 and type 2. Type 1 narcolepsy is an autoimmune condition that typically includes cataplexy, a sudden and brief loss of muscle tone. The causes of type 2 narcolepsy are unknown, and patients usually don’t experience cataplexy.
Xywav is an approved medication for individuals ages 7 and older experiencing cataplexy or excessive sleepiness related to narcolepsy. It contains several salts with oxybate, a compound that slows brain activity. Scientists believe it may improve nighttime sleep, potentially easing daytime symptoms. Compared with other oxybate medications for narcolepsy, Xywav has less sodium.
DUET involved people with narcolepsy types 1 and 2
The DUET study “aimed to assess changes in nighttime sleep and daytime symptoms in people with narcolepsy taking [Xywav],” the researchers wrote.
A total of 26 people with type 1 narcolepsy and 29 with type 2 narcolepsy started the study. All had been off oxybates for at least two weeks.
For the first two through eight weeks of the trial, clinicians adjusted the Xywav dose, with the goal of optimizing effectiveness and minimizing side effects. After deciding on a stable dose level, participants received that dose, delivered as two nightly treatments, for two weeks, followed by eight days on optimized Xywav.
The variable-dose adjustment period reflected common clinical practices but resulted in participants having different total treatment times, a potential limitation of the trial. The researchers noted, however, that “the capture of real-world clinical data was deemed an essential design element for this study.”
Of the participants who started the study, 34 completed the full treatment protocol without exceeding a prespecified nightly dose, the scientists noted.
On several rating scales, participants reported decreases in both daytime and nighttime sleep symptoms. This included significant decreases on the Epworth Sleepiness Scale (ESS), corresponding with less daytime sleepiness, for both narcolepsy types.
“The reductions in overall ESS score associated with [Xywav] treatment observed in DUET are meaningful for patients, as these were much greater than the minimal clinically important difference … for the ESS,” the researchers wrote. By the end of the trial, the median ESS score was within the range of normal sleepiness in people without narcolepsy.
Participants also reported improvements in nighttime sleep quality and decreases in overall disease severity.
New data underscore safety, effectiveness of Xywav
In addition to subjective ratings, the investigators collected sleep study data before and after treatment. This included the amount of time spent in each sleep stage.
After treatment, participants experienced significantly fewer transitions from deeper to lighter sleep stages during the night. They also spent significantly more time in N3, the deepest type of non-REM sleep, during which the body undergoes repair. These results held for both narcolepsy types.
Alongside the increase in N3 sleep time, there was a significant decrease in REM sleep time after treatment. However, “the clinical significance of this decrease in REM sleep percentage in participants with narcolepsy taking [Xywav] is not understood,” the researchers wrote. One of the possible explanations the team mentioned is a compensatory change related to the increase in N3 sleep.
These findings augment those from the pivotal trial [of Xywav] by demonstrating similar effectiveness … across people with narcolepsy type 1 or type 2.
Among the participants who started the study, 55% experienced at least one safety concern related to treatment. The most common side effects were nausea, dizziness, headaches, drowsiness, and vomiting, all consistent with the known safety profile of Xywav.
According to the researchers, these new DUET data add to the safety and efficacy evidence gathered in a pivotal Phase 3 clinical trial (NCT03030599) that had supported U.S. approval of Xywav for adults.
“These findings augment those from the pivotal trial by demonstrating similar effectiveness of low-sodium oxybate across people with narcolepsy type 1 or type 2,” the scientists wrote.
However, the study had several limitations, the team noted, including the lack of a control group. This makes it more difficult to determine if the effects on symptoms were specifically related to Xywav.
In the future, the researchers hope to use DUET data to assess how the total time on treatment, including the dose adjustment period, influences Xywav’s effectiveness.
