The US Food and Drug Administration (FDA) today approved a new indication for Xywav for idiopathic hypersomnia (IH) in adults. IH is an uncommon chronic sleep disorder that causes people to be excessively sleepy during the day even after a good night’s sleep. Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution is already approved for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years or older with narcolepsy.

“A novel indication for Xywav is significant as the FDA has never granted an approval for idiopathic hypersomnia,” says Eric Bastings, MD, deputy director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a release. “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.”

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

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%).

“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,” says Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals, marketers of Xywav, in a release. “Xywav is a meaningful treatment for patients as demonstrated by the statistically significant results from the Phase 3 clinical trial. We are proud to build on our leadership in sleep medicine and, with this approval, are expanding beyond our Xywav narcolepsy indications to bring this treatment to adults living with idiopathic hypersomnia who currently have no FDA-approved options available. This milestone exemplifies our patient-focused R&D strategy and internal development capabilities, and underscores oxybate as a key growth opportunity for Jazz. With this launch we will have achieved our goal of five product launches in two years.”

Yves Dauvilliers, MD, director of the Sleep Disorders Centre at the Gui de Chauliac Hospital in Montpellier, France, and lead investigator of the Phase 3 study, says in a release, “The clinical program for Xywav has demonstrated that this lower-sodium oxybate is an effective therapy for the treatment of idiopathic hypersomnia. Having an FDA-approved treatment option that manages symptoms associated with idiopathic hypersomnia, including excessive daytime sleepiness and severe sleep inertia, is a significant step forward for patients. Xywav fulfills an unmet need for those diagnosed with this sleep disorder, offering them management of their debilitating symptoms.”

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 has occurred in adult patients taking sodium oxybate.

Because of the potential risks associated with Xywav, 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. Xywav will not be available in retail pharmacies.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition. Today’s FDA approval is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” says Diane Powell, board chair and chief executive officer of the Hypersomnia Foundation, in a release. “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.”

Xywav received Fast Track designation by the FDA in September 2020 for the treatment of idiopathic hypersomnia and was granted Priority Review designation as part of the supplemental New Drug Application (sNDA) acceptance in April 2021. This milestone marks the second FDA approval for Xywav since it was first approved in July 2020 for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.

Xywav can be administered as a twice- or once-nightly regimen for the treatment of idiopathic hypersomnia in adults. To optimize response, a patient’s healthcare provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability.

A Nurse Case Management program is available for people taking Xyrem and Xywav to help address questions about their treatment. With this program, dedicated nurse case managers support patients from the very beginning of their treatment experience, and education is tailored to each person’s needs.

The JazzCares Patient Assistance Program may be able to provide free product to those without insurance or insurance coverage who meet certain income and other eligibility criteria.

The full Prescribing Information, including Boxed Warning, and Medication Guide are available online.