Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the U.S. Food and Drug Administration (FDA) approved Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution for the treatment of idiopathic hypersomnia in adults.1 The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following Risk Evaluation and Mitigation Strategies (REMS) implementation.

"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, chairman and chief executive officer of Jazz Pharmaceuticals. "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."

Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by chronic excessive daytime sleepiness (the inability to stay awake and alert during the day resulting in the irrepressible need to sleep or unplanned lapses into sleep or drowsiness). In addition to excessive daytime sleepiness, symptoms may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent reentries into sleep, confusion and irritability), a core symptom of idiopathic hypersomnia, as well as prolonged, non-restorative nighttime sleep, cognitive impairment, and long and unrefreshing naps.2,3,4,5 An estimated 37,000 people in the U.S. have been diagnosed with IH and are actively seeking healthcare.6

"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, M.D., director of the Sleep Disorders Centre at the Gui de Chauliac Hospital in Montpellier, France, and lead investigator of the Phase 3 study. "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."

"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," said Diane Powell, board chair and chief executive officer 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."

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 seven years of age and older with narcolepsy.

This FDA approval is based on the global Phase 3 double-blind, multicenter, placebo-controlled, randomized withdrawal study that demonstrated the efficacy and safety of Xywav for the treatment of idiopathic hypersomnia in adults. In the study, Xywav demonstrated statistically significant and clinically meaningful differences compared to placebo in change in the primary endpoint of Epworth Sleepiness Scale score (p-value <0.0001) and secondary endpoints of Patient Global Impression of Change (p-value <0.0001) and the Idiopathic Hypersomnia Severity Scale (p-value <0.0001).7

The most common adverse reactions in adults (≥5%) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue and tremor. Please see below for additional safety information.

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.

Xywav has a Boxed Warning as a central nervous system (CNS) depressant, and for its potential for abuse and misuse. Because of the risks of CNS depression and abuse and misuse, Xywav is available only through a restricted program called the Xywav and Xyrem REMS.

Jazz is committed to the safe distribution and use of our medicines, including a well-controlled distribution system for its oxybate medicines. The Xywav and Xyrem REMS was developed with the FDA and designed to ensure that Xywav and Xyrem are provided to patients securely and that patients are educated on the appropriate use of the medicines, understand the risks and safe use conditions of these medicines, and agree to follow the requirements of the Xywav and Xyrem REMS. Both prescribers and patients must enroll in the program.

Improving care and patient support are priorities to Jazz. 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.

Jazz is also committed to removing barriers to access for eligible, commercially or privately insured patients through JazzCares' Savings Program. Additionally, 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.

About Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution

Xywav, also known as JZP258, is a lower-sodium oxybate approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy and for the treatment of idiopathic hypersomnia in adults. In June 2021, the FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy. The Office of Orphan Product Development (OOPD) at the FDA also published its summary of clinical superiority findings for Xywav for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy by means of greater safety compared to Xyrem? (sodium oxybate). The decision of the OOPD is based on FDA findings that Xywav provides a greatly reduced chronic sodium burden compared to Xyrem. There are no head-to-head data for Xywav and Xyrem. Xywav is comprised of a unique composition of cations resulting in 92 percent less sodium, or a reduction of approximately 1,000 to 1,500 mg/night, than sodium oxybate at the recommended adult dosage range of 6 to 9 grams. While the exact mechanism of action of Xywav is unknown, it is hypothesized that the therapeutic effects of Xywav on cataplexy and excessive daytime sleepiness are mediated through GABAB actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.1 The U.S. Drug Enforcement Agency (DEA) has designated Xywav as a Schedule III medicine. The DEA defines Schedule III drugs, substances, or chemicals as drugs with a moderate to low potential for physical and psychological dependence.1,8