General Information

Xyrem (sodium oxybate) is an oral solution approved for the treatment of cataplexy associated with narcolepsy. Cataplexy is a debilitating symptom of narcolepsy characterized by the sudden partial or total loss of muscle control in response to extreme emotional stimuli such as laughter, anger, or surprise.

Sodium oxybate, a naturally occurring neurotransmitter in the brain involved in sleep regulation, is a central nervous system (CNS) depressant and a gamma hydroxybutyrate (GHB), a known drug of abuse. In addition, Xyrem may cause confusion and other neuropsychiatric side effects even at recommended doses. Due to these factors, Xyrem is considered a Schedule III controlled substance and will be distributed only in accordance with stringent FDA regulations.

Clinical Results

Xyrem was evaluated at 3 g, 6 g, and 9 g doses in a in a placebo-controlled, double-blind study. 136 subjects suffering from cataplexy associated with narcolepsy recorded their symptoms over a baseline period of two to three weeks after which they were treated with one of the three doses of Xyrem or placebo for a four-week period. Results of this study showed a 68.6% reduction in the median number of cataplexy attacks in subjects treated with 9 g dose of Xyrem compared to baseline. When compared to placebo, subjects receiving the 9 g dose of Xyrem showed a highly statistically significant clinical improvement. The 6 g dose of Xyrem approached significance, while the 3 g dose of Xyrem showed no statistical significance when compared to placebo. In a follow-on trial, in which 118 subjects continued taking Xyrem at clinically effective levels, the 6 g and 9 g Xyrem groups demonstrated maximum improvement at seven weeks and then sustained the clinical benefit throughout the rest of the 30-week treatment period.

Results also indicated that Xyrem is effective in reducing excessive daytime sleepiness (EDS), the secondary endpoint of the trials. As of Xyrem's July 2002 FDA approval date, a phase IIIb clinical trial for the EDS indication was ongoing.

Side Effects

The use of sodium oxybate is associated with confusion and other neuropsychiatric events. In clinical trials, adverse events included, but were not limited to:

• 
  
• dizziness
• headache
• nausea
• pain
• sleep disorder
• confusion
• infection
• vomiting
• urinary incontinence

Abuse of sodium oxybate has been linked to more serious CNS adverse events, such as seizure, respiratory depression, and profound decreases in level of consciousness, with instances of coma and death.

Mechanism of Action

The precise mechanism by which sodium oxybate produces an effect on cataplexy is unknown.

Additional Information

For more information about Xyrem, please visit:

• the Orphan Medical web site at: www.orphan.com