27 July 2020 - - The US Food and Drug Administration approved Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution for the treatment of cataplexy or excessive daytime sleepiness in patients seven years of age and older with narcolepsy, Dublin-based Jazz Pharmaceuticals plc (NASDAQ: JAZZ) said.

Xywav is an oxybate product with a unique composition of cations resulting in 92 % less sodium or approximately 1,000 to 1,500 mg/night than sodium oxybate at the recommended dosage range of 6 to 9 grams.

The company plans to launch Xywav by the end of the year following Risk Evaluation and Mitigation Strategy implementation. Jazz is committed to ensuring access to our medicines and will work to secure the broadest access possible for appropriate patients.

The FDA approval of Xywav is based on a global Phase 3 double-blind, placebo-controlled, randomized-withdrawal, multicenter study that demonstrated the efficacy and safety of Xywav in the treatment of cataplexy and EDS in patients with narcolepsy. In the study, which enrolled 201 patients, Xywav demonstrated highly statistically significant differences in weekly number of cataplexy attacks and Epworth Sleepiness Scale scores compared to placebo.

Multiple Xywav dosing options are available for adult and pediatric patients. Prescribers can titrate Xywav into unequal doses taken over the course of the night.

When patients start Xywav after sodium oxybate, Xywav treatment is initiated at the same dose and regimen as sodium oxybate (gram for gram) and titrated as needed based on efficacy and tolerability.

Xywav makes it possible for patients to have a lower-sodium oxybate treatment option.

Sodium oxybate carries warnings about its high sodium content,10 and was previously the only product approved to treat both cataplexy and EDS in patients with narcolepsy seven years of age and older and designated as a standard of care for the treatment of cataplexy and EDS by the American Academy of Sleep Medicine.

With the goal of establishing a new standard of care, Xywav was developed to provide people with narcolepsy an oxybate therapy with lower sodium, and does not carry warnings about sodium content.

Xywav has a Boxed Warning as a central nervous system 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 under a REMS called the Xywav and Xyrem REMS Program.

Most common adverse reactions in adults were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety and vomiting.

Narcolepsy is a chronic neurologic condition with no cure and the illness burden can have a far-reaching impact on a patient's health over time.

As an established leader in sleep medicine, Jazz is commited to raising awareness about narcolepsy and helping patients find strategies to manage this sleep disorder.

The US Drug Enforcement Agency 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.

About Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution
Xywav, also known as JZP-258, is approved by the US Food and Drug Administration for the treatment of cataplexy or excessive daytime sleepiness in patients seven years of age and older with narcolepsy.

It is also being studied for the treatment of idiopathic hypersomnia in adult patients. 

Xywav is comprised of a unique composition of cations resulting in 92 % less sodium, or approximately 1,000 to 1,500 mg/night, than sodium oxybate at the recommended dosage range of 6 to 9 grams. 

Xywav has the same oxybate concentration as sodium oxybate and includes a mix of calcium, magnesium, potassium and sodium cations.

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.