FDA Approves Expanded Use for Sodium Oxybate in Cataplexy, Excessive Daytime Sleepiness in Pediatric Narcolepsy

Jazz Pharmaceuticals announced that the FDA approved its supplemental new drug application expanding the currently approved indication for 0.5 g per mL sodium oxybate (Xyrem) oral solution, CIII, to include pediatric narcolepsy patients 7 years and up with cataplexy or excessive daytime sleepiness.

The efficacy and safety of Xyrem for treatment of cataplexy or excessive daytime sleepiness in pediatric patients with narcolepsy were established in the EXPRESS, a phase 2/3 pivotal study.

"Xyrem is the only FDA-approved treatment available for excessive daytime sleepiness and cataplexy in narcolepsy for adult patients," Jed Black, MD, senior vice president, Sleep and CNS Medicine at Jazz Pharmaceuticals and adjunct professor, Stanford Center for Sleep Sciences and Medicine, said in a statement.¹ "In a pivotal study we demonstrated both safety and efficacy of Xyrem in pediatric patients with narcolepsy. We are pleased to lead the sleep community in advancing the science and identifying meaningful treatment options for children and adolescents."

The EXPRESS study enrolled participants 7 to 17 years of age with narcolepsy with cataplexy. Eligible participants were either prescribed Xyrem or were Xyrem-naïve at study entry. Xyrem-naïve participants underwent open-label titration to determine a tolerable and effective dose.

Following a stable dose period, all study participants endured a 2-week, double-blind, randomized-withdrawal period and were randomly assigned to either remain on Xyrem at the given stable dose or receive placebo.

The primary efficacy endpoint was change in the weekly number of cataplexy attacks from baseline to the end of the double-blind period, while a key secondary endpoint included the change in excessive daytime sleepiness as assessed by the Epworth Sleepiness Scale for Children and Adolescents from baseline to the of the double-blind period. After the completion of the randomized-withdrawal period, participants then were enrolled in an open-label safety period for an additional 47 weeks. The total study duration lasted up to 1 year.

Participants randomized to placebo, withdrawn from Xyrem (32 [51%] of 63 patients) experienced increased weekly cataplexy attacks (median increase of 12.7 attacks per week [Q1, Q3 = 3.4, 19.8]) in comparison to those who continued treatment with Xyrem (median increase of 0.3 attacks per week [Q1, Q3 = -1.0, 2.5]; P <.0001).

There are no new safety concerns reported; the safety profile in children and adolescents was similar to that reported in adults. The open-label portion of the study is ongoing. At the time of data cut in February 2017, the most common treatment-emergent adverse effects >5% were enuresis, nausea, vomiting, headache, decreased weight, decreased appetite, nasopharyngitis and dizziness, and 2 serious treatment-emergent adverse effects occurred both in sodium oxybate-naïve participants during the open-label titration period, acute psychosis (severe) and suicidal ideation (moderate in severity). Both serious treatment-emergent adverse effects resolved after reducing the dose or discontinuing Xyrem, respectively.

Xyrem is taken at night and divided into 2 doses. Pediatric patients should be given the first dose at bedtime or after an initial period of sleep while in bed and should lie down immediately. The second dose should be given 2.5 to 4 hours after the first dose. Patients should remain in bed after both doses.²

Due to the risk of central nervous system depression, and abuse and misuse, Xyrem, the sodium salt of gamma-hydroxybutyrate (GHB) is only available through restricted risk evaluation mitigation strategy (REMS) programs. Xyrem was first approved in the United States in 2002 for cataplexy and excessive daytime sleepiness in narcolepsy in adults.

REFERENCE

Jazz Pharmaceuticals Announces FDA Approval of Xyrem® (sodium

oxybate) for the Treatment of Cataplexy or Excessive Daytime Sleepiness in Pediatric Narcolepsy Patients [news release]. Dublin, Ireland: Jazz Pharmaceuticals; Oct. 29, 2018. http://investor.jazzpharma.com/phoenix.zhtml?c=210227&p=RssLanding&cat=news&id=2373861. Accessed Oct. 29, 2018.

2. XYREM (sodium

oxybate

) oral solution, CIII [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals; 2018. http://pp.jazzpharma.com/pi/xyrem.en.USPI.pdf. Accessed Oct. 29, 2018.