By SPC News Staff

The FDA granted a new indication for calcium, magnesium, potassium and sodium oxybates (Xywav, Jazz Pharmaceuticals) for idiopathic hypersomnia (IH) in adults. 

Idiopathic hypersomnia is an uncommon chronic sleep disorder that causes people to be excessively sleepy during the day, even after a good night’s sleep. The oral solution was approved in 2020 for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age or older with narcolepsy.

The effectiveness of the treatment was evaluated in a double-blind, placebo-controlled, randomized withdrawal study in 154 adult patients (ages 19-75 years) with IH. In the clinical study, patients who were randomized to switch from the oral solution to placebo experienced worsening on measures of sleepiness and symptoms of IH compared with patients randomized to continue treatment.

In the study, the oral solution demonstrated statistically significant and clinically meaningful differences compared with placebo in change in the primary end point of Epworth Sleepiness Scale score (P<0.0001) and secondary end points of Patient Global Impression of Change (P<0.0001) and the Idiopathic Hypersomnia Severity Scale (P<0.0001).

“The clinical program for Xywav has demonstrated that this lower-sodium oxybate is an effective therapy for the treatment of idiopathic hypersomnia,” said Yves Dauvilliers, MD, the director of the Sleep Disorders Centre at the Gui de Chauliac Hospital, in Montpellier, France, and lead investigator of the phase 3 study. 

“Idiopathic hypersomnia can have a significant impact on the social, educational and occupational functioning of people living with the condition,” said Diane Powell, the board chair and CEO of the Hypersomnia Foundation. “Our mission and values have consistently centered around supporting patients and scientific discovery and this announcement truly provides a sense of hope for those living with idiopathic hypersomnia.”

In the clinical trial for IH, the most common adverse events as a result of the treatment observed in the study included nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%) and vomiting (10.4%).

Xywav has a boxed warning for central nervous system depression and abuse and misuse. The active moiety of Xywav is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule I controlled substance. Abuse or misuse of illicit GHB has been associated with serious side effects, including seizures, trouble breathing, changes in alertness, coma and death. Clinically significant respiratory depression and reduced level of alertness have occurred in adult patients taking sodium oxybate.

Because of the potential risks associated with the drug, it is subject to strict safety controls on prescribing and dispensing under a program called a Risk Evaluation and Mitigation Strategy (REMS). Specifically, under the Xywav REMS, it can be prescribed only by a certified prescriber, and dispensed only to an enrolled patient by a certified pharmacy. 

Only a certified pharmacy that ships directly to patients can dispense Xywav and will not be available in retail pharmacies.

In addition to excessive daytime sleepiness, symptoms may include severe sleep inertia or sleep drunkenness, as well as prolonged, non-restorative nighttime sleep, cognitive impairment, and long and unrefreshing naps. An estimated 37,000 people in the United States have been diagnosed with IH and are actively seeking health care (Neurotherapeutics 2020 Sep 8. doi:10.1007/s13311-020-00919-1).

Xywav can be administered as a twice- or once-nightly regimen for the treatment of IH in adults. To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to four hours later, and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability.