Jazz Pharmaceuticals to Present Expansive Research Demonstrating Comprehensive Treatment Benefits of Xywav® (calcium, magnesium, potassium, and sodium oxybates) in Sleep Conditions and Associated ...

Nineteen abstracts, including eleven late-breaking abstracts, underscore Jazz's leadership and extensive research in sleep medicine, and ongoing commitment to advancing the treatment of narcolepsy and idiopathic hypersomnia

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DUBLIN, May 29, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that nineteen abstracts, including eleven late-breaking abstracts will be presented at SLEEP 2025, the 39^th annual meeting of the Associated Professional Sleep Societies (APSS) being held June 8-11, 2025, in Seattle.

Research to be presented at the meeting include dual late-breaking poster and oral presentations, which highlight the extensive Phase 4 data evaluating the effectiveness of low-sodium oxybate, Xywav^® (calcium, magnesium, potassium, and sodium oxybates) oral solution in patients with narcolepsy and idiopathic hypersomnia (IH). These presentations include the first interim results from the open-label, single arm XYLO trial that evaluated ambulatory and office blood pressure changes in patients with narcolepsy after switching from a twice-nightly high-sodium oxybate oral solution to low-sodium oxybate, Xywav. Two additional presentations share novel results from the open-label, single arm DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) trial, which assessed Xywav on multiple sleep parameters, including the first presentation of polysomnography (PSG) outcomes in adults with IH. Additional data evaluated the effectiveness and safety of Xywav in a cohort of narcolepsy patients whose doses were optimized to greater than 9 grams (with twice-nightly dosing). The Xywav label recommends a maximum nightly dose of 9 grams per night.

"Jazz prioritizes a holistic approach to patient health, continuously deepening our understanding of how to support patients with challenging sleep disorders, as well as mitigate associated comorbidities," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer of Jazz Pharmaceuticals. "The extensive research presented at SLEEP 2025, underscores our commitment to patient-centric care, including the development of low-sodium Xywav, which is particularly important given the impact of sodium intake and existing cardiovascular risks among patients with narcolepsy or idiopathic hypersomnia."

Additional highlights at SLEEP 2025 include:

• Two late-breaking poster presentations describing results from the CHIME study, which evaluated real-world, patient-reported outcomes, including treatment adherence, effectiveness, and satisfaction among adults with narcolepsy or IH (reported separately) taking Xywav.
• A late-breaking claims analysis that describes self-reported prevalence, severity, and impact of sleep inertia among individuals diagnosed with IH. 
• Two additional late-breaking poster presentations showcasing findings from INTREPID, a retrospective cohort study that examined Optum Market Clarity data from 2007–2023 to assess treatment patterns and changes in alerting agent claims among patients with narcolepsy or IH during the full study period and following the approval of Xywav.
• Two poster presentations showcasing sleep architecture results from the DUET trial, which demonstrated the effectiveness of Xywav on improvements in sleep quality among patients with IH or narcolepsy.
• Two poster presentations report interim results from the LYRICAL study, which examined real-world and patient-reported data showing patients in both the narcolepsy and IH cohorts taking Xywav experience symptom improvements, improved quality of life and high global treatment satisfaction.

The SLEEP 2025 abstracts are available online at sleepmeeting.org/abstract-supplements.

A full list of Jazz Pharmaceuticals' presentations follows below:

About Xywav^® (calcium, magnesium, potassium, and sodium oxybates) oral solution
Xywav is the only low-sodium oxybate approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of cataplexy or EDS 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 EDS in patients 7 years of age and older with narcolepsy by means of greater cardiovascular safety compared to Xyrem^® (sodium oxybate) oral solution. The decision of the OOPD is based on the FDA findings that Xywav provides a greatly reduced chronic sodium burden compared to Xyrem. Xywav has 131 mg of sodium at the maximum recommended nightly dose whereas other high sodium oxybates have 1640 mg at the equivalent dose. Xywav is comprised of a unique composition of cations resulting in 92% less sodium, or a reduction of approximately 1,000 to 1,500 mg/night at the recommended dose range of 6 g to 9 g/night. Xywav is the only oxybate therapy that does not carry a warning in the label related to use in patients sensitive to high sodium intake.

Xywav is also the first and only U.S. FDA-approved treatment option for idiopathic hypersomnia in adults. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of idiopathic hypersomnia in adults. Xywav is the only FDA-approved treatment studied across the multiple symptoms of idiopathic hypersomnia, such as EDS, sleep inertia (severe grogginess or confusion when waking up), long sleep duration and cognitive impairment. Xywav can be administered as a twice- or once-nightly regimen for the treatment of idiopathic hypersomnia in adults.

The exact mechanism of action of Xywav in the treatment of adults with idiopathic hypersomnia and of cataplexy and EDS in narcolepsy is unknown. It is hypothesized that the therapeutic effects of Xywav are mediated through GABA_B actions during sleep at noradrenergic and dopaminergic neurons, as well as 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.^1,2 Because of the risks of central nervous system (CNS) depression and abuse and misuse, Xywav is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS.

Important Safety Information for Xywav

Contraindications
XYWAV is contraindicated

• in combination with sedative hypnotics or alcohol and
• in patients with succinic semialdehyde dehydrogenase deficiency.

Warnings and Precautions
Central Nervous System Depression

The concurrent use of XYWAV with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If use of these CNS depressants in combination with XYWAV is required, dose reduction or discontinuation of one or more CNS depressants (including XYWAV) should be considered. In addition, if short-term use of an opioid (eg, post- or perioperative) is required, interruption of treatment with XYWAV should be considered.

After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter.

Abuse and Misuse
XYWAV is a Schedule Ill controlled substance. The active moiety of XYWAV is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule I controlled substance. Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death. The rapid onset of sedation, coupled with the amnestic features of GHB particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (eg, assault victim). Physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely.

XYWAV and XYREM REMS
Because of the risks of central nervous system depression and abuse and misuse, XYWAV is available only through a restricted distribution program called the XYWAV and XYREM REMS.

Notable requirements of the XYWAV and XYREM REMS include the following:

• Healthcare Providers who prescribe XYWAV are specially certified
• XYWAV will be dispensed only by the central pharmacy that is specially certified
• XYWAV will be dispensed and shipped only to patients who are enrolled in the XYWAV and XYREM REMS with documentation of safe use

Further information is available at www.XYWAVXYREMREMS.com or 1-866-997-3688.

Respiratory Depression and Sleep-Disordered Breathing
XYWAV may impair respiratory drive, especially in patients with compromised respiratory function. In overdoses of oxybate and with illicit use of GHB, life-threatening respiratory depression has been reported. Increased apnea and reduced oxygenation may occur with XYWAV administration in adult and pediatric patients. A significant increase in the number of central apneas and clinically significant oxygen desaturation may occur in patients with obstructive sleep apnea treated with XYWAV. Prescribers should be aware that sleep-related breathing disorders tend to be more prevalent in obese patients, in men, in postmenopausal women not on hormone replacement therapy, and among patients with narcolepsy.

Depression and Suicidality
In Study 1, the randomized-withdrawal clinical trial in adult patients with narcolepsy (n=201), depression and depressed mood were reported in 3% and 4%, respectively, of patients treated with XYWAV. Two patients (1%) discontinued XYWAV because of depression. In most cases, no change in XYWAV treatment was required. 

In Study 2, the randomized-withdrawal clinical trial in adult patients with idiopathic hypersomnia (n=154), depression and depressed mood were reported in 1% and 3%, respectively, of patients treated with XYWAV. All patients continued XYWAV treatment.

Two suicides and two attempted suicides occurred in adult clinical trials with oxybate (same active moiety as XYWAV). One patient experienced suicidal ideation and two patients reported depression in a pediatric clinical trial with oxybate. These events occurred in patients with and without previous histories of depressive disorders. The emergence of depression in patients treated with XYWAV requires careful and immediate evaluation. Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV.

Other Behavioral or Psychiatric Adverse Reactions
In Study 1, confusion and anxiety occurred in 1% and 5% of patients with narcolepsy treated with   XYWAV, respectively. One patient experienced visual hallucinations and confusion after ingesting approximately 9 grams of XYWAV.

In Study 2, confusion and anxiety occurred in 3% and 16% of patients with idiopathic hypersomnia, respectively. One patient experienced visual hallucinations, which led to discontinuation of XYWAV. 

Other neuropsychiatric reactions reported with oxybate (same active moiety as XYWAV) in adult or pediatric clinical trials and in the postmarketing setting include hallucinations, paranoia, psychosis, aggression, agitation, confusion and anxiety. The emergence or increase in the occurrence of behavioral or psychiatric events in patients taking XYWAV should be carefully monitored.

Parasomnias
Parasomnias can occur in patients taking XYWAV.

In Study 1 and Study 2, parasomnias, including sleepwalking, were reported in 6% and 5% of adult patients treated with XYWAV, respectively. 

In a clinical trial of XYREM (same active moiety as XYWAV) in adult patients with narcolepsy, five instances of sleepwalking with potential injury or significant injury were reported. Parasomnias, including sleepwalking, have been reported in a pediatric clinical trial with sodium oxybate (same active moiety as XYWAV) and in postmarketing experience with sodium oxybate.

Episodes of sleepwalking should be fully evaluated and appropriate interventions considered.

Most Common Adverse Reactions
The most common adverse reactions (occurring in ≥5% of XYWAV-treated patients in adult clinical trials in either narcolepsy or IH) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor. 

In the pediatric clinical trial with XYREM (same active moiety as XYWAV) that included pediatric patients 7 to 17 years of age with narcolepsy, the most common adverse reactions (≥5%) were nausea (20%), enuresis (19%), vomiting (18%), headache (17%), weight decreased (13%), decreased appetite (9%), dizziness (8%), and sleepwalking (6%). The overall adverse reaction profile of XYREM in the pediatric clinical trial was similar to that seen in the adult clinical trial program. The safety profile in pediatric patients with XYWAV is expected to be similar to that of adult patients treated with XYWAV and to that of pediatric patients treated with XYREM.

Additional Adverse Reactions
Adverse reactions that occurred in 2-<5% of adult patients treated with XYWAV in the Open­ Label Titration and Stable Dose Periods of the randomized-withdrawal study in adult patients with narcolepsy with cataplexy (Study 1) were fatigue, dry mouth, depressed mood, enuresis, irritability, paresthesia, depression, tremor, somnolence, and muscle spasms. Adverse reactions occurring in 2-<5% of patients treated with XYWAV in the IH study include balance disorder, muscle spasms, fall, paresthesia, snoring, weight decreased, bruxism, confusional state, depressed mood, feeling drunk, and irritability.

Adverse reactions that occurred in ≥2% of patients in clinical studies with oxybate (but not in Study 1) and which may be relevant for XYWAV, were pain, feeling drunk, pain in extremity, cataplexy, disturbance in attention, sleep paralysis, and disorientation.

Discontinuation: In Study 1, 9 of 201 patients (4%) reported adverse reactions that led to withdrawal from the study (anxiety, decreased appetite, depressed mood, depression, fatigue, headache, irritability, nausea, pain in extremity, parasomnia, somnolence, and vomiting). The most common adverse reaction leading to discontinuation was nausea (1.5%). In Study 2, 17 of 154 (11%) patients across all study periods (excluding placebo during the DB RWP) (up to 42 weeks) reported adverse reactions that led to withdrawal from the study (anxiety, nausea, insomnia, vomiting, fatigue, feeling abnormal, fall, decreased appetite, dizziness, paresthesia, tremor, parasomnia, confusional state, hallucination visual, and irritability). The most common adverse reaction leading to discontinuation was anxiety (3.2%). In Study 1 and Study 2, the majority of adverse reactions leading to discontinuation began during the first few weeks of treatment.

In the pediatric clinical trial with XYREM (same active moiety as XYWAV), 7 of 104 patients reported adverse reactions that led to withdrawal from the study (hallucination, tactile; suicidal ideation; weight decreased; sleep apnea syndrome; affect lability; anger, anxiety, depression; and headache).

Drug Interactions
XYWAV is contraindicated in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of XYWAV.

Concomitant use of sodium oxybate with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study. A similar increase in exposure is expected with concomitant use of XYWAV and divalproex sodium; therefore, an initial dose reduction of XYWAV is recommended when used concomitantly with divalproex sodium. Prescribers are advised to monitor patient response closely and adjust dose accordingly if concomitant use of XYWAV and divalproex sodium is warranted.

Pregnancy and Lactation
There are no adequate data on the developmental risk associated with the use of XYWAV or sodium oxybate in pregnant women. XYWAV should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. GHB is excreted in human milk after oral administration of sodium oxybate. There is insufficient information on the risk to a breastfed infant, and there is insufficient information on milk production in nursing mothers. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for XYWAV and any potential adverse effects on the breastfed infant from XYWAV or from the underlying maternal condition.

Pediatric Use
The safety and effectiveness of XYWAV for the treatment of cataplexy or excessive daytime sleepiness in pediatric patients 7 years of age and older with narcolepsy have been established. XYWAV has not been studied in a pediatric clinical trial for narcolepsy or IH. Use of XYWAV in pediatric patients 7 years of age and older with narcolepsy is supported by evidence from an adequate and well­controlled study of sodium oxybate in pediatric patients 7 to 17 years of age, a study in adults showing a treatment effect of XYWAV similar to that observed with sodium oxybate, pharmacokinetic data of sodium oxybate from adult and pediatric patients, and pharmacokinetic data of XYWAV from healthy adult volunteers.

Safety and effectiveness of XYWAV in pediatric patients below the age of 7 years with narcolepsy have not been established.

Safety and effectiveness of XYWAV for the treatment of idiopathic hypersomnia in pediatric patients have not been established.

Geriatric Use
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment
The starting dose of XYWAV should be reduced in patients with liver impairment.

Dosage Modification in Patients with Hepatic Impairment: The recommended starting dosage in patients with hepatic impairment is one-half of the original dosage per night, administered orally, divided into two doses.

Dependence and Tolerance
There have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illict use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium. These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required.

In the clinical trial experience with XYREM in narcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time. In the XYWAV clinical trial in adult narcolepsy/cataplexy patients at recommended doses, one patient reported insomnia following abrupt discontinuation of XYWAV. In the XYWAV clinical trial in adult idiopathic hypersomnia patients at recommended doses, six patients reported insomnia, two patients reported early insomnia, and one patient reported visual and auditory hallucinations following abrupt discontinuation of XYWAV.

Tolerance to XYWAV has not been systematically studied in controlled clinical trials. There have been some case reports of symptoms of tolerance developing after illicit use at dosages far in excess of the recommended XYWAV dosage regimen.

Please see full Prescribing Information, including BOXED Warning here: https://pp.jazzpharma.com/pi/xywav.en.USPI.pdf

About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information.

Contacts:

Media:
Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
U.S. +1 215 867 4948

Investors:
Jeff Macdonald
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
InvestorInfo@jazzpharma.com
Ireland +353 1 634 3211
U.S. +1 650 496 2717

References:

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