Abstracts Accepted for Presentation at the 31st Annual
Meeting of the Associated Professional Sleep Societies LLC
(APSS) in June 2017
DUBLIN, March 20, 2017 /PRNewswire/ -- Jazz
Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive
efficacy results from two global multicenter studies in adult
patients with excessive sleepiness associated with obstructive
sleep apnea (OSA). JZP-110 demonstrated highly statistically
significant differences in the co-primary efficacy endpoints in the
TONES 3 study at the 300 mg, 150 mg, 75 mg and 37.5 mg dose arms
and in the TONES 4 study in the combined JZP-110 treatment arm (300
mg, 150 mg, and 75 mg doses) compared to placebo. Based on
the preliminary safety analysis, the most commonly reported adverse
events (AEs) in these studies were consistent with those previously
described in the Phase 2 clinical studies evaluating JZP-110 in
narcolepsy.
"There is an important unmet need for OSA patients who
experience excessive sleepiness, and the robust magnitude of
effect, when taken together with the preliminary safety findings,
suggest that JZP-110 could be an important treatment option for
this population," said Karen Smith,
M.D., Ph.D., global head of research and development and chief
medical officer of Jazz Pharmaceuticals. "We are grateful to
the patients and the investigators who participated in these
studies and look forward to presenting the results from the Phase 3
OSA studies at the APSS meeting in June. We expect to
announce preliminary results from our Phase 3 TONES 2 study
evaluating JZP-110 in excessive sleepiness associated with
narcolepsy in the second quarter of 2017. Subject to final
data analysis and regulatory discussions with FDA, we continue to
target NDA submission in late 2017."
"Independent of CPAP therapy for OSA, there can be a level of
excessive sleepiness associated with reduced quality of life and
'fall asleep' accidents, with increased public risks of drowsy
driving," said Kingman Strohl, M.D.,
Professor of Medicine, University Hospitals Case Medical Center and
Case School of Medicine, Cleveland OH. "Given this, clinical
recognition and meaningful treatment options are needed for OSA
patients who experience excessive sleepiness."
The Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES)
Phase 3 program is comprised of four studies, two in OSA, one in
narcolepsy and one open-label, long-term safety and maintenance of
efficacy study. The two Phase 3 OSA studies enrolled 652
total patients.
Efficacy Results of TONES 3 Study
The TONES 3 study,
or 14-003, is a 5-arm, parallel-group study evaluating four doses
of JZP-110 (300 mg, 150 mg, 75 mg and 37.5 mg) and placebo for a
12-week period. The study enrolled 476 patients and was
powered to detect differences between placebo and the 300 mg and
150 mg dose arms.
In TONES 3, JZP-110 demonstrated highly statistically
significant improvement in the co-primary endpoints of Maintenance
of Wakefulness test (MWT) and Epworth Sleepiness scale (ESS) at all
doses. In addition, the key secondary endpoint of Patient
Global Impression of Change (PGIc) scale demonstrated a highly
statistically significant improvement in the 300 mg, 150 mg and 75
mg doses versus placebo. On the co-primary endpoints of MWT
and ESS, the study demonstrated that treatment with JZP-110
significantly increased the patients' ability to stay awake and
significantly decreased patients' subjective levels of sleepiness,
respectively, compared to placebo. These effects were
maintained throughout the course of the study.
Efficacy Results of TONES 4 Study
The TONES 4 study,
or 14-004, is a six-week study in which eligible subjects received
four weeks of open-label treatment, and at the end of week 4, 126
patients who reported "much" or "very much" improvement on the PGIc
scale and who had numerical improvements on the MWT and ESS at week
4 were then randomized 1:1 to receive either the same dose of
JZP-110 received in the stable dose phase, or placebo, for two
weeks in the randomized withdrawal phase.
In TONES 4, patients randomized to continue on JZP-110
maintained efficacy, while those randomized to placebo experienced
a loss of efficacy, as measured by the co-primary and key secondary
endpoints.
Preliminary Safety Results of TONES 3 and TONES 4
Studies
Based on a preliminary safety analysis, the most
commonly reported adverse events were headache, nausea, decreased
appetite, dry mouth, anxiety, dizziness, insomnia, nasopharyngitis,
and palpitations. There were six patients with serious
adverse events (SAEs), two patients on placebo and four on
JZP-110. None of these was deemed a treatment-related adverse
event as assessed by the investigators. Additional safety
information will be available based on the final analyses of the
JZP-110 program, including results of the open-label, long-term
safety and maintenance of efficacy study.
About the TONES 3 and TONES 4 Studies
TONES 3 is a
12-week, 5-arm, parallel-group, double-blind, placebo-controlled,
randomized Phase 3 study, evaluating the safety and efficacy of
JZP-110 at 300 mg, 150 mg, 75 mg and 37.5 mg compared to placebo.
The co-primary endpoints are the change in mean sleep latency
on the MWT and the change in the ESS score, from baseline to week
12. The key secondary endpoint is the change on the PGIc
scale, a patient-reported measure of improvement, worsening, or no
change in overall condition from baseline to week 12.
TONES 4 is a six-week Phase 3 study comprising a two-week
flexible-dose titration phase followed by two weeks at stable dose,
and then a two-week, placebo-controlled, double-blind randomized
withdrawal phase. In this study, patients were first titrated
to a maximum tolerated dose over a two-week period and then
continued on that dose for two weeks in a stable dose phase.
The primary analyses evaluated the difference between JZP-110
treatment versus placebo on the co-primary endpoints of MWT and
ESS, measured from the end of the stable dose phase at week 4 to
the end of the randomized withdrawal phase at week 6.
About OSA and Excessive Sleepiness
OSA is a highly
prevalent disease with excessive sleepiness reported as one of the
most frequent symptoms. Excessive sleepiness is associated
with impairments in function, vigilance, concentration, thinking,
social interactions and quality of life. Positive airway
pressure (PAP) therapy, commonly referred to as continuous positive
airway pressure (CPAP), has been shown to be an effective therapy
for sleep-related airway obstruction, with frequent improvement in
excessive sleepiness in many patients; however, approximately
25-50% of patients with OSA experience difficulty with PAP therapy.
In addition, many patients treated with PAP therapy continue
to experience persistent sleepiness, despite successful use of
PAP.
About JZP-110
JZP-110 is a selective dopamine and
norepinephrine reuptake inhibitor (DNRI) in late-stage development
for treatment of excessive sleepiness in adult patients with
narcolepsy or OSA. Jazz Pharmaceuticals has worldwide
development, manufacturing, and commercialization rights to
JZP-110, excluding certain jurisdictions in Asia. JZP-110 has orphan drug
designation in the United States
for narcolepsy. Across the entire JZP-110 development
program, over 2,000 subjects have enrolled in 20 studies. The
JZP-110 Phase 3 clinical program includes two studies evaluating
excessive sleepiness in adult patients with OSA, one study
evaluating excessive sleepiness in adult patients with narcolepsy
and an open-label, long-term safety and maintenance of efficacy
study. Enrollment is complete in all studies that are
expected to support the planned JZP-110 New Drug Application (NDA)
submission to the U.S. Food and Drug Administration (FDA).
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc
(Nasdaq: JAZZ) is an international biopharmaceutical company
focused on improving patients' lives by identifying, developing and
commercializing meaningful products that address unmet medical
needs. The company has a diverse portfolio of products and
product candidates, with a focus in the areas of sleep and
hematology/oncology. In these areas, Jazz Pharmaceuticals markets
Xyrem® (sodium oxybate) oral solution, Erwinaze® (asparaginase
Erwinia chrysanthemi) and Defitelio® (defibrotide sodium) in
the U.S. and markets Erwinase® and Defitelio® (defibrotide) in
countries outside the U.S. For more information, please visit
www.jazzpharmaceuticals.com.
"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 JZP-110 as a potential treatment for
excessive sleepiness in adult patients with OSA, the expected
announcement of preliminary results from the company's Phase 3
TONES 2 study evaluating JZP-110 in excessive sleepiness associated
with narcolepsy, the company's plans for submission of an NDA for
JZP-110 with the FDA, the timing of such events and activities, 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 for JZP-110, and effectively
commercializing JZP-110, 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 Annual Report on Form 10-K for the period
ended December 31, 2016 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
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company undertakes no obligation to update or supplement any
forward-looking statements to reflect actual results, new
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circumstances that exist after the date as of which the
forward-looking statements were made.