JZP-258 achieves primary and key secondary endpoints
demonstrating highly statistically
significant differences in weekly number of cataplexy
attacks and Epworth Sleepiness Scale scores compared to
placebo
DUBLIN, March 26, 2019 /PRNewswire/ -- Jazz
Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive
top-line results from the global, double-blind, placebo-controlled,
randomized-withdrawal, multicenter Phase 3 study evaluating
the efficacy and safety of JZP-258 for the treatment of cataplexy
and excessive daytime sleepiness (EDS) in adult patients with
narcolepsy. JZP-258 is a novel oxybate product candidate with a
unique composition of cations resulting in 92% less sodium than
Xyrem® (sodium oxybate).
The Phase 3 study demonstrated highly statistically significant
differences in the primary endpoint that measured the change in the
weekly number of cataplexy attacks and the key secondary endpoint
of change in Epworth Sleepiness Scale (ESS) score with JZP-258
compared to placebo. In this study, patients were randomized to
either continue JZP-258 or to receive placebo. Patients randomized
to JZP-258 showed clinically meaningful maintenance of efficacy for
both cataplexy and EDS, while a statistically significant worsening
for both cataplexy and ESS endpoints was observed in the placebo
group compared with JZP-258.
The safety profile of JZP-258 is consistent with sodium oxybate.
The most commonly reported treatment-emergent adverse events that
occurred in ≥ 5% of patients who received JZP-258 were
headache, nausea, dizziness, cataplexy, nasopharyngitis, decreased
appetite, influenza, diarrhea and vomiting. Two patients
experienced serious adverse events (SAEs) that were considered by
the investigator to be treatment related.
Jazz will submit the Phase 3 study data for presentation at an
upcoming medical meeting. Data from the completed Phase 3 study and
interim data from the ongoing 24-week open-label, safety study will
be included in the planned submission of a New Drug Application
(NDA) to the U.S. Food and Drug Administration (FDA).
"Jazz is committed to developing new treatment options that
serve unmet needs for patients living with sleep disorders,
including JZP-258, a novel oxybate product candidate with 92% less
sodium than sodium oxybate," said Jed Black, M.D., senior vice
president, Sleep and CNS Medicine at Jazz
Pharmaceuticals and adjunct professor, Stanford
University Medical Center, Stanford Center for Sleep Sciences
and Medicine. "We are deeply grateful to the patients and
investigators who participated in this study, and we will meet with
the FDA to discuss the Phase 3 results in narcolepsy and our NDA
submission plans, with the goal of making JZP-258 available to
narcolepsy patients."
"Narcolepsy is a chronic, debilitating disease and is associated
with an increased risk of comorbidities," said Michael Thorpy, M.D., director, Sleep-Wake
Disorders Center, Montefiore Health System in Bronx, New York. "An extensive body of
evidence has established that excessive consumption of sodium is
linked with an increased risk of stroke, cardiovascular disease and
other adverse outcomes. Patients with narcolepsy may require
lifelong medication, and there is a need for a new, low-sodium
oxybate formulation."
About the Phase 3 Study
The Phase 3 study of JZP-258
was a global, double-blind, placebo-controlled,
randomized-withdrawal, multicenter study evaluating the efficacy
and safety of JZP-258 in the treatment of cataplexy in adult
patients with narcolepsy. The primary endpoint was the change in
the weekly number of cataplexy attacks and the key secondary
endpoint was the change in the ESS score from JZP-258 and
placebo over the randomized-withdrawal period. The study enrolled
201 patients and randomized 134 patients, comprising a
heterogeneous patient population which included those previously
treated with Xyrem, naïve to Xyrem, and with or without other
anti-cataplectic treatments. A randomized-withdrawal study design
aims to measure efficacy – specifically, maintenance of effect –
for patients who remain on active treatment and worsening for
patients who switch to placebo.
The study design included a titration period of up to 12 weeks,
a JZP-258 stable-dose period of two weeks, followed by a 1:1
randomization to either JZP-258 or placebo for 2 weeks. After
the completion of the double-blind, placebo-controlled treatment
period, patients had the opportunity to receive JZP-258 in an
optional 24 week open-label safety extension period. More
information about the study design is available at
www.clinicaltrials.gov (identifier: NCT03030599).
About JZP-258
JZP-258 is an investigational product
being evaluated in adult patients for the treatment of cataplexy
and excessive daytime sleepiness in narcolepsy, as well as for the
treatment of idiopathic hypersomnia. JZP-258 is a novel oxybate
product candidate with a unique composition of cations resulting in
92% less sodium than Xyrem® (sodium oxybate). The
mechanism of action of JZP-258 is not fully understood, but it is
hypothesized that the therapeutic effects of JZP-258 on sleep/wake
symptoms are mediated through modulation of GABAB during
sleep.
About Narcolepsy
Narcolepsy is a chronic, debilitating
neurological disorder characterized by excessive daytime
sleepiness, 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. It is estimated that more than 50% of
patients 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 Excessive daytime sleepiness is the
primary symptom of narcolepsy and is present in all people with the
disorder.4 There are five primary symptoms of
narcolepsy, including excessive daytime sleepiness, cataplexy,
hallucinations, sleep paralysis and sleep disruption.5
While all patients with narcolepsy experience excessive daytime
sleepiness, they may not experience all five
symptoms.6,7 Excessive daytime sleepiness is
characterized by the inability to stay awake and alert during the
day resulting in unplanned lapses into sleep or
drowsiness.2,4,8
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.6,7,9
Although many emotions can potentially lead to
cataplexy, those associated with mirth are usually the most
potent.6 Cataplexy occurs in about 70% of patients
with narcolepsy.10 Presentation differs widely
among patients, ranging from sporadic partial attacks triggered by
laughter to frequent complete collapse brought about by a variety
of emotions.6,7 Complete collapse is generally less
common.7 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).6,7,9,10
About Jazz Pharmaceuticals plc
Jazz Pharmaceuticals
plc (Nasdaq: JAZZ), a global biopharmaceutical company, is
dedicated to developing life-changing medicines for people with
limited or no options. As a leader in sleep medicine and with a
growing hematology/oncology portfolio, Jazz has a diverse portfolio
of products and product candidates in development, and is focused
on transforming biopharmaceutical discoveries into novel medicines.
Jazz Pharmaceuticals markets Xyrem® (sodium oxybate)
oral solution, Erwinaze® (asparaginase Erwinia
chrysanthemi), Defitelio® (defibrotide sodium) and
Vyxeos® (daunorubicin and cytarabine) liposome for
injection in the U.S. and markets
Erwinase®, Defitelio® (defibrotide) and
Vyxeos® 44 mg/100 mg powder for concentrate for solution
for infusion in countries outside the U.S. For country-specific
product information, please visit
www.jazzpharmaceuticals.com/medicines. For more information, please
visit www.jazzpharmaceuticals.com and follow us on Twitter at
@JazzPharma.
"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 the company's planned submission of an NDA
for JZP-258 with the FDA, the company's goal of making JZP-258
available to narcolepsy 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, risks and uncertainties associated
with: pharmaceutical product development and clinical success
thereof; the regulatory approval process, including the risk that
the company may be unable to obtain approval by the FDA of its
planned NDA for JZP-258 in a timely manner or at all; effectively
commercializing JZP-258; and other risks and uncertainties
affecting the company and its development programs, 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 Quarterly Report on Form 10-K for the year
ended December 31, 2018 and future
filings and reports by the company. 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. The forward-looking statements herein are
made only as of the date hereof or as of the dates indicated in the
forward-looking statements, even if they are subsequently made
available by the company on its website or otherwise. The
company undertakes no obligation to update or supplement any
forward-looking statements to reflect actual results, new
information, future events, changes in its expectations or other
circumstances that exist after the date as of which the
forward-looking statements were made.
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. Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL,
ed. Sleep: A Comprehensive Handbook. Hoboken, NJ:
Wiley and Sons, Inc.; 2006:145-149.
6. 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.
7. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of
narcolepsy. Clin Chest
Med. 2010;31(2):371-381.
8. Ahmed I, Thorpy, M. Sleepiness: Causes, Consequences and
Treatment, ed. Cambridge University Press. 2011:36-49.
9. 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.
10. 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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