Jazz Pharmaceuticals Announces FDA Acceptance of New Drug Application for JZP-258 for Cataplexy and Excessive Daytime Sleepiness Associated with Narcolepsy

DUBLIN, March 25, 2020 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the U.S. Food and Drug Administration (FDA) accepted for filing with Priority Review the company's New Drug Application (NDA) seeking marketing approval for JZP-258, an investigational medicine for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. JZP-258 is a novel oxybate product candidate with a unique composition of cations resulting in 92%, or approximately 1,000 to 1,500 milligrams, less sodium than Xyrem^® (sodium oxybate). Xyrem is the only available product approved to treat both cataplexy and EDS in patients with narcolepsy ages 7 years and older and is the standard of care for treatment of cataplexy. The Prescription Drug User Fee Act (PDUFA) goal date for an FDA decision is July 21, 2020.

"We developed JZP-258 to be a safer and long-term treatment option for patients. JZP-258 represents between 1,000 and 1,500 milligrams daily reduction of sodium for patients currently treated with Xyrem, depending on the dose," said Robert Iannone, M.D., M.S.C.E., executive vice president, research and development of Jazz Pharmaceuticals. "Given the broad scientific consensus that reducing daily sodium consumption is associated with clinically meaningful reductions in blood pressure and cardiovascular disease risk, we believe that JZP-258 has the potential to be an important treatment option for patients living with the life-long condition of narcolepsy. Narcolepsy patients are known to be at increased risk of comorbidities, including obesity, hypertension, diabetes and dyslipidemia.^9,10,11,12"

About Narcolepsy
Narcolepsy is a chronic, debilitating neurological disorder characterized by EDS and the inability to regulate sleep-wake cycles normally.¹ It affects an estimated one in 2,000 people in the United States, with symptoms typically appearing in childhood or adolescence. It is estimated that more than 50% of people with narcolepsy have not been diagnosed.² Studies have shown it may take 10 years or more for people with narcolepsy to receive a diagnosis.³ There are five primary symptoms of narcolepsy, including EDS, cataplexy, disrupted nighttime sleep, sleep-related hallucinations, and sleep paralysis.⁶ While all people with narcolepsy experience EDS, not all individuals with narcolepsy experience all five symptoms.^7,8 EDS is the primary symptom of narcolepsy and is present in all people with the disorder.⁴ EDS is characterized by the inability to stay awake and alert during the day resulting in drowsiness and unplanned lapses into sleep.^2,4,5 There is also an increased prevalence of cardiometabolic comorbidities, including obesity, hypertension, diabetes and dyslipidemia, in patients with narcolepsy.^9,10,11,12

About Cataplexy
Cataplexy, the most specific symptom of narcolepsy, is the sudden, generally brief (<2 minutes) loss of muscle tone with retained consciousness. It is usually triggered by strong emotions, such as laughter, surprise, or anger.^7,8,13 Although many emotions can potentially lead to cataplexy, those associated with mirth are usually the most potent.⁷ Cataplexy occurs in about 70% of people with narcolepsy.¹⁴ Presentation differs widely among people with narcolepsy, ranging from sporadic partial attacks triggered by laughter to frequent complete collapse brought about by a variety of emotions.^7,8 Complete collapse is less common.⁸ More commonly, episodes of cataplexy involve only certain muscle groups, such as arms and legs (e.g., knees buckling), the head and neck (e.g., head dropping), or the face and jaw (e.g., sagging, slurred speech, eyelid drooping).^7,8,13,14

About JZP-258
JZP-258 is an investigational medicine developed for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years of age and older with narcolepsy, as well as for the treatment of idiopathic hypersomnia in adult patients. JZP-258 is a novel oxybate product candidate with a unique composition of cations resulting in 92%, or approximately 1,000 to 1,500 milligrams, less sodium than Xyrem with each nightly dose. JZP-258 has the same oxybate concentration as Xyrem and includes other cations, including calcium, magnesium and potassium. While the exact mechanism of action of JZP-258 is not fully understood, it is hypothesized that the therapeutic effects of JZP-258 on sleep/wake symptoms are mediated through modulation of GABA_B during sleep.

About Jazz Pharmaceuticals plc
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company dedicated to developing life-changing medicines for people with serious diseases — often with limited or no options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in key therapeutic areas. Our focus is in neuroscience, including sleep medicine and movement disorders, and in oncology, including hematologic and solid tumors. We actively explore new options for patients including novel compounds, small molecule advancements, biologics and innovative delivery technologies. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in more than 90 countries. For more information, please visit www.jazzpharmaceuticals.com and follow @JazzPharma on Twitter.

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995
This press release contains forward-looking statements, including, but not limited to, statements related to Jazz Pharmaceuticals' belief in JZP-258's potential to be an important treatment option, which was developed to be a safer and life-long treatment option for patients and other statements that are not historical facts. These forward-looking statements are based on the company's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the risk that JZP-258 may not be approved by FDA by the PDUFA date, or otherwise in a timely manner, or at all; effectively commercializing JZP-258, if approved; and other risks and uncertainties affecting the company, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including the company's Annual Report on Form 10-K for the year ended December 31, 2019 and future filings and reports. Other risks and uncertainties of which the company is not currently aware may also affect the company's forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated.

Media Contact:
Jacqueline Kirby, Vice President, Corporate Affairs & Government Relations
Ireland +353 1 697 2141         U.S. +1 215 867 4910

Investor Contact:
Kathee Littrell, Vice President, Investor Relations
Ireland +353 1 634 7887         U.S. +1 650 496 2717

References:

1. Thorpy M, Krieger A. Delayed diagnosis of narcolepsy: characterization and impact. Sleep Medicine. 2014;15(5):502–507.
2. Ahmed I, Thorpy, M. Clinical Features, Diagnosis and Treatment of Narcolepsy. Clin Chest Med. 2010;31(2):371-381.
3. Morrish E, King M, et al. Factors associated with a delay in the diagnosis of narcolepsy. Sleep Medicine. 2004;5(1):37-41.
4. American Academy of Sleep Medicine. The International Classification of Sleep Disorders. Third Edition (ICSD-3). 2014.
5. Ahmed I, Thorpy, M. Sleepiness: Causes, Consequences and Treatment, ed. Cambridge University Press. 2011:36-49.
6. Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149.
7. American Academy of Sleep Medicine. Central disorders of hypersomnolence. In: The International Classification of Sleep Disorders – Third Edition (ICSD-3). Darien, IL: American Academy of Sleep Medicine; 2014.
8. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
9. Cohen A, et al. Sleep Med. 2018;43:14-18.
10. Black J, et al. Sleep Med. 2017;33:13-18.
11. Jennum P, et al. Sleep. 2013;36(6):835-840.
12. Ohayon MM. Sleep Med. 2013;14(6):488-492.
13. 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.
14. 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.

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