Jazz Pharmaceuticals plc announced that the U.S. Food and Drug Administration (FDA) approved Xywav™ (calcium, magnesium, potassium, and sodium oxybates) oral solution on July 21, 2020 for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.1,2 Xywav is an oxybate product with a unique composition of cations resulting in 92 percent less sodium – or approximately 1,000 to 1,500 mg/night – than sodium oxybate at the recommended dosage range of 6 to 9 grams.1
The company plans to launch Xywav by the end of the year following Risk Evaluation and Mitigation Strategy (REMS) 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 (p<0.0001) in weekly number of cataplexy attacks and Epworth Sleepiness Scale scores compared to placebo.3
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.1
“Based on the efficacy demonstrated in the clinical program, the approval of Xywav is important for people living with cataplexy or EDS associated with narcolepsy.1 Xywav makes it possible for patients to have a lower-sodium oxybate treatment option. This may help patients taking sodium oxybate better align with daily sodium intake recommendations including those by the American Heart Association,4” said Richard K. Bogan, MD, FCCP, FAASM, associate clinical professor at the University of South Carolina School of Medicine, a medical officer at SleepMed in Columbia, SC and lead investigator of the Phase 3 study. “The average American consumes too much sodium.5 Excess sodium intake has been linked with increases in blood pressure, hypertension, stroke, and other cardiovascular disease.6,7,8,9”
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 7 years of age and older11 and designated as a standard of care for the treatment of cataplexy and EDS by the American Academy of Sleep Medicine.12 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 (≥5%) were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety and vomiting.1
“We have been working for nearly a decade to develop Xywav, a unique oxybate product with a significant reduction in sodium. We are proud to advance the science behind our sleep research program in order to continue making a difference for people living with narcolepsy,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “Jazz is committed to addressing unmet needs in sleep medicine, which includes our innovative and long-standing oxybate program.”
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.13,14,15,16 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.
“Many people with narcolepsy can go years before being properly diagnosed and this can have a significant impact to their everyday life,” said Julie Flygare, president and CEO of Project Sleep. “Narcolepsy is a life-long condition so it is important to have new options to help treat EDS and cataplexy.”
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.17
More information about Xywav, including Full Prescribing Information and Medication Guide, is available here.
- Xywav (calcium, magnesium, potassium and sodium oxybates) oral solution Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
- Thorpy MJ. Recently Approved and Upcoming Treatments for Narcolepsy. CNS Drugs. 2020;34(1):9-27. doi:10.1007/s40263-019-00689-1.
- Bogan R. Efficacy and Safety of JZP-258 in a Phase 3 Double-Blind, Placebo-Controlled, Randomised Withdrawal Study in Adults With Narcolepsy With Cataplexy. Oral presentation at World Sleep 2019; September 2019; Vancouver, CA.
- American Heart Association. 2018, May 23. How much sodium should I eat per day? https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/sodium/how-much-sodium-should-i-eat-per-day. Accessed July 2020.
- Jackson SL, King SM, Zhao L, Cogswell ME. Prevalence of Excess Sodium Intake in the United States – NHANES, 2009-2012. MMWR. Morbidity and Mortality Weekly Report. 2016 Jan;64(52):1393-1397. DOI: 10.15585/mmwr.mm6452a1.
- Elliott P, Stamler J, Nichols R, et al. Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. Intersalt Cooperative Research Group [published correction appears in BMJ 1997 Aug 23;315(7106):458]. BMJ. 1996;312(7041):1249-1253. doi:10.1136/bmj.312.7041.1249.
- Mente A, O’Donnell MJ, Rangarajan S, et al. Association of Urinary Sodium and Potassium Excretion with Blood Pressure. N Engl J Med 2014; 371:601-611. DOI: 10.1056/NEJMoa1311989.
- Gardener H, Rundek T, Wright CB, Elkind MS, Sacco RL. Dietary sodium and risk of stroke in the Northern Manhattan study. Stroke. 2012;43(5):1200-1205. Doi:10.1161/STROKEAHA.111.641043.
- Institute of Medicine. 2005. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: The National Academies Press. https://doi.org/10.17226/10925.
- Xyrem (sodium oxybate) oral solution. Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
- Abad VC. An evaluation of sodium oxybate as a treatment option for narcolepsy. Expert Opin Pharmacother. 2019;20(10):1189-1199. Doi:10.1080/14656566.2019.1617273.
- Morgenthaler T, et al. Practice Parameters for the Treatment of Narcolepsy and other Hypersomnias of Central Origin. An American Academy of Sleep Medicine Report. SLEEP, Vol. 30, No. 12, 2007.
- Black J, Reaven NL, Funk SE, et al. Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. Sleep Med. 2017;33:13-18. doi:10.1016/j.sleep.2016.04.004.
- Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med. 2013;14(6):488-492. doi:10.1016/j.sleep.2013.03.002.
- National Institute of Neurological Disorders and Stroke (NINDS). 2020, March 16. Narcolepsy Fact Sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/fact-sheets/narcolepsy-fact-sheet. Accessed March 2020.
- Flores NM, Villa KF, Black J, Chervin RD, Witt EA. The Humanistic and Economic Burden of Narcolepsy. J Clin Sleep Med. 2016;12(3):401-407. doi:10.5664/jcsm.5594.
- United States Drug Enforcement Agency. Drug Scheduling. https://www.dea.gov/drug-scheduling.
- Thorpy MJ, Bogan RK. Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications. Sleep Med. 2020;68:97-109. Doi:10.1016/j.sleep.2019.09.001.
- Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
- Plazzi G, Clawges HM, Owens JA. Clinical Characteristics and Burden of Illness in Pediatric Patients with Narcolepsy. Pediatr Neurol. 2018;85:21-32. doi:10.1016/j.pediatrneurol.2018.06.008.
- American Academy of Sleep Medicine. The International Classification of Sleep Disorders. Third Edition (ICSD-3). 2014.
- Morrish E, King M, et al. Factors associated with a delay in the diagnosis of narcolepsy. Sleep Medicine. 2004;5(1):37-41.
- Thorpy M, Krieger A. Delayed diagnosis of narcolepsy: characterization and impact. Sleep Medicine. 2014;15(5):502–507.
- Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149.
- Zhang J, Han F. Sleepiness in Narcolepsy. Sleep Med Clin. 2017;12(3):323-330. doi:10.1016/j.jsmc.2017.03.008.
- Cohen A, Mandrekar J, St Louis EK, Silber MH, Kotagal S. Comorbidities in a community sample of narcolepsy. Sleep Med. 2018;43:14-18. doi:10.1016/j.sleep.2017.11.1125.
- Jennum P, Ibsen R, Knudsen S, Kjellberg J. Comorbidity and mortality of narcolepsy: a controlled retro- and prospective national study. Sleep. 2013;36(6):835-840. Published 2013 Jun 1. doi:10.5665/sleep.2706.
- Overeem S, van Nues SJ, van der Zande WL, et al. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 2011;12(1):12-18.
- Overeem S. The clinical features of cataplexy. In: Baumann CR, Bassetti CL, Scammell TE, eds. Narcolepsy: Pathophysiology, Diagnosis, and Treatment. New York, NY: Springer Science+Business Media; 2011:283-290.
Source: Jazz Pharmaceuticals