FDA Grants New Indication to Sleep-Disorder Drug Xywav

A new indication for a well-known drug could lead to relief for patients with a rare sleep condition, but the approval is also calling to mind some of the problem associated with the drug, which will only be dispensed through a risk-mitigation protocol.

The FDA last month granted a new indication for Xywav (calcium, magnesium, potassium, and sodium oxybates), a drug whose active ingredient is a form of gamma hydroxybutyrate (GHB). Xywav had already been approved to treat cataplexy or excessive daytime sleepiness in patients ages 7 and older. The new indication is for idiopathic hypersomnia in adults, a rare condition in which patients experience excessive daytime sleepiness even when they get plenty of sleep.

“We are excited that with today's approval Xywav will become the first and only medicine indicated to treat idiopathic hypersomnia, a unique medical condition that can have significant effects on the lives of those diagnosed with the condition," said Bruce Cozadd, MBA, the chief executive at Jazz Pharmaceuticals, in a press release.

In clinical trials, the drug out-performed placebo, generating a statistically significant improvement in Epworth Sleepiness Scale and Idiopathic Hypersomnia Severity Scale scores among patients .

Xywav is an oral solution similar to Xyrem (sodium oxybate), which has also been approved to treat cataplexy and excessive daytime sleepiness. However, Xywav has 92% less sodium in each nightly dose compared to Xyrem. Both Xywav and Xyrem are marketed by Jazz Pharmaceuticals.

“Idiopathic hypersomnia is a life-long condition, and the approval of Xywav will be instrumental in providing treatment for symptoms such as excessive sleepiness and difficulty waking, and in effectively managing this debilitating disorder,” said Eric Bastings, M.D., the deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research.

The drug comes with the potential for side effects, the most common adverse events reported in the trial were nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%) and vomiting (10.4%), the FDA said.

The drug’s potential for abuse that has caused some concern. Before it was approved for sleep-related conditions, illicit versions of GHB were used recreationally, and sometimes maliciously. As a 2014 report from the Institute for Safe Medication Practices reported, the drug was one of the first known “date-rape drugs.”

GHB is now a Schedule 1 controlled substance.

The FDA approval came with conditions. The drug is subject to a risk evaluation and mitigation strategy (REMS) protocol, meaning prescribers must be certified before they can write prescriptions for the drug, and only certified pharmacies can dispense it. The drug will be available only at pharmacies that ship directly to patients.

Jazz Pharmaceuticals has also launched a Nurse Case Management program, in which nurses are available to answer patient questions and support patients taking Xywav or Xyrem.

The company has also set up a savings program and a patient assistance program to help patients obtain the drug, which The New York Times reported can cost up to $100,000 per year for nightly treatments.