First Presentation of the Phase 4 XYLO Switch Study Reports Blood Pressure Reductions in Patients with Narcolepsy When Switching from Twice-Nightly High- to Low-Sodium Oxybate

Novel Intermediate Analysis from the DUET Trial Cohort

For U.S. media and investors only

DUBLIN, June 9, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced late-breaking Phase 4 data evaluating treatment benefits of Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution in people with narcolepsy. These results are two of Jazz's four late-breaking abstracts presented today as oral presentations at SLEEP 2025. The four late-breaking abstracts, selected for their scientific quality and innovation, comprise all industry-sponsored late-breaking oral presentations selected by the Associated Professional Sleep Societies (APSS). Xywav is the only low-sodium oxybate approved by the U.S. Food and Drug Administration for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy and for adults with idiopathic hypersomnia. The Xywav label recommends a nightly dose of 6-9 grams per night.

"People living with narcolepsy have an increased risk of developing cardiovascular and cardiometabolic comorbidities," said Richard J. Kovacs, MD, MACC, Chief Medical Officer, American College of Cardiology and Q.E. and Sally Russell Professor of Cardiology, Indiana University School of Medicine, and XYLO Steering Committee member. "Results from the XYLO study reinforce the importance of monitoring cardiovascular indicators, including blood pressure, and the need to minimize exposure to excess sodium in this at-risk population. Reducing cardiovascular risk and disease is an important goal for all healthcare providers."

"People with narcolepsy live with a complex, severe disorder and often must combat excessive daytime sleepiness and associated symptoms — but the challenges they face are not only limited to sleep," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer of Jazz Pharmaceuticals. "Results from the XYLO interim analysis add to the overwhelming body of evidence demonstrating the positive implications of limiting unnecessary sodium intake, and emphasize how choosing low-sodium oxybate, Xywav, rather than twice-nightly high-sodium oxybate helps reduce excessive sodium burden, a modifiable risk factor for cardiovascular disease, in people with narcolepsy."

Phase 4 XYLO Results

The open-label, single arm Phase 4 XYLO switch trial (n=43) met its primary endpoint of change in mean 24-hour ambulatory systolic blood pressure (SBP) from baseline (taking twice-nightly high-sodium oxybate) to end-of-treatment (after six weeks on low-sodium oxybate, Xywav), with a −4.1 (−6.9, −1.4; P=0.0019) mmHg change. These results show that switching from twice-nightly high-sodium oxybate to the same dosage of low-sodium oxybate, Xywav, for approximately 6 weeks reduced daily treatment-related sodium intake and was associated with clinically meaningful blood pressure reductions in participants with narcolepsy, which was paralleled by 24-hour urinary sodium reduction. XYLO results are consistent with the extensive body of evidence on the benefits of reducing sodium intake.

The study also achieved key secondary endpoints, including mean change in ambulatory daytime SBP (-5.1 mmHg; P=0.0003) and mean change in seated resting (in-office) SBP (-9.2 mmHg; (P<0.0001). The change in mean nighttime ambulatory SBP was −2.0 (P=0.1265) mmHg. Exploratory endpoints evaluated change in 24-hour, daytime ambulatory, seated resting, and nighttime ambulatory diastolic blood pressure.

Overall, treatment-emergent adverse events (TEAEs) occurred in 32.8% of participants and were all mild or moderate in severity and consistent with the known safety profile of Xywav.

Phase 4 DUET Data

This intermediate analysis, which evaluates a cohort of adults with narcolepsy from the DUET (Develop Hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) trial, demonstrated improvements in EDS on the Epworth Sleepiness Scale, the study's primary endpoint, in 24 participants taking 9-12 grams of Xywav twice-nightly, as compared to 9 grams at baseline. The current recommended dosage of Xywav for adults with narcolepsy is 6-9 grams per night. Following dose optimization, the average Xywav dose during the stable-dose period was 11.2 g/night.

Participants with narcolepsy in this intermediate cohort analysis also experienced improvements on the Narcolepsy Severity Scale. Additionally, participants showed minimal changes in the number of central apnea events, mean oxygen saturation (SpO2) levels, or the mean percent of total sleep time with SpO2 <90% from baseline to end of treatment.

The DUET trial is a Phase 4, prospective, single-arm, open-label study to assess the effect of Xywav treatment on EDS, polysomnography parameters, and functional outcomes in adults with narcolepsy or idiopathic hypersomnia. Overall, TEAEs were all mild or moderate and consistent with the known safety profile of Xywav at lower dosages.

The full abstracts will be available online at sleepmeeting.org/abstract-supplements.

About Narcolepsy

Narcolepsy is a chronic, debilitating neurologic sleep disorder characterized by the inability to maintain continuous sleep at night and sustained wakefulness throughout the day. This leads to symptoms that can include fragmented or disrupted nighttime sleep, excessive daytime sleepiness, and cataplexy. Patients with EDS due to narcolepsy experience sleep attacks, called cataplexy, and, despite fighting the urge to sleep, may unintentionally fall asleep for short periods. These sleep attacks may happen at inappropriate or potentially dangerous times such as during driving, cycling, eating, or mid-conversation.

There is no cure for narcolepsy, therefore this EDS is lifelong and has a substantial negative impact on a person's ability to function psychologically, socially, and professionally. Patients with narcolepsy are at increased risk for hypertension, cardiometabolic morbidity, stroke, myocardial infarction, heart failure, cardiac arrest, and death. As narcolepsy is a chronic condition that requires lifelong, nightly treatment, early access to an effective, low-sodium treatment can transform lives and reduce the impact of narcolepsy on a person's physical and mental health.

About Xywav® 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 GABAB actions during sleep at noradrenergic and dopaminergic neurons, as well as thalamocortical neurons. 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. 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

WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.

Because of the risks of 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.

Contraindications

XYWAV is contraindicated.

Warnings and Precautions

Central Nervous System Depression: The concurrent use of XYWAV with other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If required, dose reduction or discontinuation of one or more CNS depressants should be considered.

Caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes, until certain that XYWAV does not adversely affect them.

Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV.

Adverse Reactions

The most common adverse reactions occurring in ≥5% of XYWAV-treated patients were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

Additional Information

Please see full Prescribing Information, including BOXED Warning here.

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.

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
Email: [email protected]
Ireland: +353 1 637 2141
U.S.: +1 215 867 4948

Investors:
Jeff Macdonald
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
Email: [email protected]
Ireland: +353 1 634 3211
U.S.: +1 650 496 2717

References:

SOURCE Jazz Pharmaceuticals plc