FDA Approves Sodium Oxybate (Xyrem) for Pediatric Narcolepsy

Deborah Brauser


October 29, 2018

The US Food and Drug Administration (FDA) has approved an expanded indication for sodium oxybate (Xyrem, Jazz Pharmaceuticals) oral solution for treating symptoms associated with pediatric narcolepsy.

The manufacturer's supplemental new drug application (NDA) was for revising the labeling to include an indication for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients aged 7 to 17 years with narcolepsy. Cataplexy is the sudden weakening or paralysis of muscles when a patient feels strong emotions.

The central nervous system depressant was previously indicated for these conditions in adult patients only. The FDA's new thumbs up of sodium oxybate "marks the first medicine approved to treat [these symptoms] in children and adolescents with narcolepsy ages seven and older," the manufacturer reported in a press release.

"Narcolepsy is often misunderstood, misrepresented, misdiagnosed, and underdiagnosed, especially in children," Claire Crisp, executive director of Wake Up Narcolepsy, said in the same release.

This expanded approval "is a significant step forward for the narcolepsy community as work to elevate awareness of the condition in children and ensure patients, both pediatric and adult, have meaningful treatment options available," added Crisp, who is also the mother of a child with narcolepsy.


The drug was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy. As reported by Medscape Medical News, the agency expanded approval in November 2005 to include treatment for EDS in these adult patients.

In July 2018, preliminary results from the multisite, phase 2/3 EXPRESS study, which assessed use of sodium oxybate for the treatment of these symptoms in pediatric patients with narcolepsy, were published in the Lancet Child and Adolescent Health.

In addition, the manufacturer presented oral and poster presentations of EXPRESS results showing efficacy and long-term safety at the SLEEP 2018 annual meeting.

The primary efficacy endpoint was change in weekly number of cataplexy attacks from baseline to end of the double-blind period. Change in EDS during the same period was a key secondary outcome. An open-label safety period of up to 47 weeks followed, for a total study duration of up to 1 year.

The participants who were randomly assigned to receive placebo experienced a greater increase in weekly cataplexy attacks compared with those who received sodium oxybate (median increase in attacks, 12.7 per week vs 0.3 per week; P < .0001).

"The safety profile...in children and adolescents in this study was similar to that reported in adults, and no new safety concerns were identified following the use of Xyrem for up to one year," the company reports.

The open-label portion of the study is ongoing. The most commonly reported treatment-related adverse events as of February 2017, time of the data cut, were nausea, vomiting, headache, decreased weight and appetite, and bed wetting. There were also two serious treatment-emergent adverse events: one case of severe acute psychosis, and one case of suicidal ideation that was judged to be moderate in severity.

In addition, scores on the 10-item Multidimensional Anxiety Scale for Children and on the Children's Depression Inventory 2nd Edition Self-Report Short Version (CDI 2:SR) "were within the average range throughout the study in participants who were Xyrem-naive and on Xyrem at study entry," the manufacturer notes.

There was "a slight downward trend observed" in mean CDI 2:SR scores over time.

High Abuse Potential

On the basis of these results, Jazz submitted a supplemental NDA to the FDA in April of this year that proposed a revision in labeling for the drug so as to include data for use in pediatric patients.

The drug is classified as a Schedule III controlled substance because its active ingredient is a form of gamma hydroxybutyrate, which has a high potential for abuse. "Abuse and misuse of Xyrem can cause serious medical problems including seizures, trouble breathing, and changes in alertness, and death," the company notes on its website.

Because of these risks, sodium oxybate is only available through a restricted risk evaluation mitigation strategy (REMS) program. In the Xyrem REMS program, prescribers of the drug must be specially certified, as do central pharmacies that dispense it.

New prescribing information notes that the drug should be administered orally twice nightly. "The recommended starting pediatric dosage, titration regimen, and maximum total nightly dosage are based on patient weight," it adds. "The dosage may be gradually titrated based on efficacy and tolerability."

"We are pleased to lead the sleep community in advancing the science and identifying meaningful treatment options for children and adolescents," Jed Black, MD, senior vice president of Sleep and CNS Medicine at Jazz Pharmaceuticals and adjunct professor at Stanford Center for Sleep Sciences and Medicine, California, said in a statement.

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