WASHINGTON, Dec. 10, 2018 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced that
HETLIOZ® (tasimelteon) improved sleep quality and
increased sleep duration in patients with Smith-Magenis Syndrome
(SMS) in a pivotal placebo controlled clinical study.
"We are extremely pleased with the results of this study of
tasimelteon in patients with Smith-Magenis Syndrome.
Tasimelteon was shown to meaningfully improve sleep in SMS
patients, addressing an unmet medical need for the most severe
symptom constellation of this rare disorder," said Mihael H. Polymeropoulos MD, Vanda's President
and Chief Executive Officer.
VEC-162-2401 was a double masked 4 week cross-over pivotal
clinical trial that studied the effects of tasimelteon versus
placebo in 25 patients with SMS. Patients were evaluated for daily
diary sleep quality (DDSQ) and for daily diary total nighttime
sleep duration (DDTST) via a parental post sleep questionnaire
(PSQ). Total nighttime sleep duration was also measured via daily
actigraphy. The study had two predefined primary endpoints: DDSQ
and DDTST.
Tasimelteon met the primary endpoint of improvement in the 50%
worst sleep quality (DDSQ) (p=0.0139) and also showed improvement
on the primary endpoint of 50% worst total nighttime sleep duration
(DDTST) (p=0.0556) (Table 1).
Tasimelteon demonstrated significant improvement in overall
sleep quality (DDSQ) (p=0.0155) and overall total nighttime sleep
duration (DDTST) (p=0.0134). Tasimelteon improved the overall total
nighttime sleep duration (DDTST) by an average of approximately 41
minutes per night, a highly clinically meaningful effect.
Given that most of the baseline nights were of shortened sleep
duration, tasimelteon also improved sleep duration for the best
half of the baseline nights versus placebo (50% best DDTST, 46.6
min, p=0.0052). Tasimelteon also showed significant improvement in
subjective measures of total nighttime sleep duration via
actigraphy, for 50% worst TST (p=0.0309) and overall TST (p=0.0218)
(Table 1).
In this study, aberrant behaviors improved from baseline on both
tasimelteon and placebo but likely due to the relative short
duration of the study the differences were not significant between
the two groups. In a longer open label study of tasimelteon
in SMS, patients were treated for a period of approximately 27
weeks following a 6 week baseline evaluation. In that study,
significant improvements from baseline were observed in sleep
quality (DDSQ, p=0.0105) as well as in aberrant behaviors (Aberrant
Behavior Checklist, p=0.0006)1.
The improvements in sleep quality and sleep duration
demonstrated in the 2401 study were consistent across patients with
chromosomal deletions of various lengths as well as a single
patient with a point mutation in the RAI1 gene on chromosome 17p.
The detailed results are expected to be presented in upcoming
meetings and peer reviewed publications.
"Individuals with Smith-Magenis syndrome have significantly
impaired sleep with altered sleep-wake cycles. This chronic
sleep deprivation impacts cognitive and behavioral function on a
daily basis. The sleep disturbance that occurs in this disorder
impacts the entire family. The improved sleep duration and
sleep quality with tasimelteon as shown in this study can provide a
significant improvement to quality of life for individuals and
families affected by this complex genetic condition" said Dr.
Sarah Elsea, Professor, Baylor College of Medicine and Chair, PRISMS
Professional Advisory Board.
Vanda wants to extend its appreciation to all who worked
tirelessly on this multi-year project and especially the patients,
their families, their advocates and the PRISMS organization.
VEC-162-2401 is the largest placebo controlled study ever
conducted demonstrating significant sleep improvements in patients
with SMS. The U.S. Food and Drug Administration has granted
orphan drug designation for tasimelteon for the treatment of
SMS. Vanda intends to meet with regulatory authorities and
seek marketing authorization for the treatment of SMS patients with
tasimelteon.
Table 1. Study VEC-162-2401 Results Summary*
Endpoints
|
Description
|
Tasimelteon
(n=25)
|
Placebo
(n=25)
|
Difference
p-value
|
Subjective
|
|
|
|
|
Sleep
Quality
|
DDSQ Worst
50%*
|
0.67
|
0.27
|
0.0139
|
(Scale
1-5)
|
DDSQ
Overall
|
0.55
|
0.22
|
0.0155
|
|
|
|
|
|
Sleep
Duration
|
DDTST Worst
50%*
|
36.1
|
17.6
|
0.0556
|
(minutes)
|
DDTST Best
50%
|
46.6
|
23.4
|
0.0052
|
|
DDTST
Overall
|
40.9
|
19.8
|
0.0134
|
Objective
|
|
|
|
|
Sleep
Duration
|
Actigraphy TST Worst
50%
|
22.3
|
2.4
|
0.0309
|
(minutes)
|
Actigraphy TST
Overall
|
20.1
|
1.9
|
0.0218
|
*Primary endpoint
For DDSQ, DDTST, Actigraphy TST, the values shown are
changes from baseline.
HETLIOZ® is currently approved for the treatment
of Non-24 Hour Sleep Wake Disorder. For a review of the current
prescribing information of HETLIOZ® please
visit www.hetlioz.com.
HETLIOZ® IS NOT CURRENTLY APPROVED BY ANY
REGULATORY AUTHORITY FOR THE TREATMENT OF SMS.
Conference Call
The Vanda management team will host a conference call and live
webcast today, Monday, December 10,
2018, at 8:30 AM ET to discuss
these updates. Investors can call 1-888-771-4371 (domestic)
or 1-847-585-4405 (international) and use passcode 47969899. A
replay of the call will be available on Monday, December 10, 2018, beginning at
11:00 AM ET and will be accessible
until Monday, December 17, 2018, at
11:59 PM ET. The replay call-in
number is 1-888-843-7419 for domestic callers and 1-630-652-3042
for international callers. The passcode number is 47969899.
The conference call will be broadcast simultaneously on Vanda's
website. Investors should click on the Investor Relations tab and
are advised to go to the website at least 15 minutes early to
register, download, and install any necessary software or
presentations. The call will also be archived on Vanda's website
for a period of 30 days.
About Smith-Magenis Syndrome
Smith-Magenis Syndrome (SMS) is a developmental disorder that is
caused by a small deletion of human chromosome 17p
2,3. In more rare cases SMS is caused by a point
mutation in the RAI1 gene which resides in the deleted
region. SMS is estimated to affect 1/15,000-25,000
individuals. SMS is usually not inherited but rather is due
to a de-novo deletion. Patients with SMS present with a
number of physical, mental and behavioral problems. The most common
symptom of SMS is a severe sleep disorder associated with
significant disruption in the lives of patients and their
families.
About HETLIOZ® (tasimelteon)
HETLIOZ® (tasimelteon) is a melatonin receptor
agonist. HETLIOZ® has been granted market
authorization by the U.S. Food and Drug Administration and the
European Medicines Agency. For full U.S. prescribing information,
please visit www.hetlioz.com.
Important Safety Information
The most common adverse reactions (incidence >5% and at least
twice as high on HETLIOZ® (tasimelteon) than on
placebo) were headache, increased alanine aminotransferase,
nightmares or unusual dreams, and upper respiratory or urinary
tract infection. The risk of adverse reactions may be greater in
elderly (>65 years) patients than younger patients because
exposure to HETLIOZ® is increased by approximately
2-fold compared with younger patients.
Indication
HETLIOZ® is indicated for the treatment of
Non-24-Hour Sleep-Wake Disorder (Non-24).
Important Safety Information
HETLIOZ® may cause somnolence: After taking
HETLIOZ®, patients should limit their activity to
preparing for going to bed, because HETLIOZ® can
potentially impair the performance of activities requiring complete
mental alertness.
The most common adverse reactions (incidence >5% and at least
twice as high on HETLIOZ® than on placebo) were
headache, increased alanine aminotransferase, nightmares or unusual
dreams, and upper respiratory or urinary tract infection. The risk
of adverse reactions may be greater in elderly (>65 years)
patients than younger patients because exposure to
HETLIOZ® is increased by approximately 2-fold
compared with younger patients.
Use of HETLIOZ® should be avoided in combination
with fluvoxamine or other strong CYP1A2 inhibitors, because of a
potentially large increase in exposure of HETLIOZ®, and
a greater risk of adverse reactions.
HETLIOZ® should be avoided in combination with
rifampin or other CYP3A4 inducers, because of a potentially large
decrease in exposure of HETLIOZ®, with reduced
efficacy.
There are no adequate and well-controlled studies of
HETLIOZ® in pregnant women. Based on animal data,
HETLIOZ® may cause fetal harm.
HETLIOZ® should be used during pregnancy only if
the potential benefit justifies the potential risks. Caution should
be exercised when HETLIOZ® is administered to a
nursing woman.
HETLIOZ® has not been studied in patients with
severe hepatic impairment and is not recommended in these
patients.
Safety and effectiveness of HETLIOZ® in
pediatric patients have not been established.
About Vanda
Vanda is a global biopharmaceutical company focused on the
development and commercialization of innovative therapies to
address high unmet medical needs and improve the lives of patients.
For more on Vanda Pharmaceuticals Inc., please
visit www.vandapharma.com.
Abbreviations
SMS
Smith-Magenis Syndrome
TST
Total Sleep Time
SQ
Sleep Quality
DDTST
Daily Diary Total Sleep Time
DDSQ
Daily Diary Sleep Quality
References
1. Hull, J.T., Polymeropoulos, C.M., Cho, Y., Xiao, C.,
Polymeropoulos, M.H (2017, October 7-11). Tasimelteon
Improves Sleep Quality and Behavior in Individuals With Smith
Magenis Syndrome (SMS) in an Open-Label Study. Poster
Presentation at World Sleep Society (14th world sleep
congress). Prague, Czech
Republic
2. Williams, S. R., Zies, D., Mullegama, S. V, Grotewiel, M.
S., & Elsea, S. H. (2012). Smith-Magenis syndrome results in
disruption of CLOCK gene transcription and reveals an integral role
for RAI1 in the maintenance of circadian rhythmicity. Am.J
Hum.Genet., 90(1537–6605), 941–949.
3. Gropman, A. L., Duncan, W. C., & Smith, A. C. (2006).
Neurologic and developmental features of the Smith-Magenis syndrome
(del 17p11.2). Pediatr.Neurol., 34(0887–8994),
337–350.
HETLIOZ® is Vanda's registered trademark. Any other
trademarks, registered marks and trade names and service marks
appearing in this release are the property of their respective
holders.
FORWARD LOOKING STATEMENTS
Various statements in this release are "forward-looking
statements" under the securities laws. Forward-looking statements
are based upon current expectations that involve risks, changes in
circumstances, assumptions and uncertainties. Important factors
that could cause actual results to differ materially from those
reflected in Vanda's forward-looking statements include
tasimeltion's potential to be approved by regulatory authorities
and become a pharmacological option in the treatment of sleep
disruptions in patients with SMS; and other factors that are
described in the "Risk Factors" and "Management's Discussion and
Analysis of Financial Condition and Results of Operations" sections
of Vanda's annual report on Form 10-K for the fiscal year ended
December 31, 2017 and quarterly
report on Form 10-Q for the quarter ended September 30, 2018, which are on file with the
Securities and Exchange Commission (SEC) and available on the SEC's
website at www.sec.gov. In addition to the risks described above
and in Vanda's annual report on Form 10-K and quarterly reports on
Form 10-Q, other unknown or unpredictable factors also could affect
Vanda's results. There can be no assurance that the actual results
or developments anticipated by Vanda will be realized or, even if
substantially realized, that they will have the expected
consequences to, or effects on, Vanda. Therefore, no assurance can
be given that the outcomes stated in such forward-looking
statements and estimates will be achieved.
All written and verbal forward-looking statements attributable
to Vanda or any person acting on its behalf are expressly qualified
in their entirety by the cautionary statements contained or
referred to herein. Vanda cautions investors not to rely too
heavily on the forward-looking statements Vanda makes or that are
made on its behalf. The information in this release is
provided only as of the date of this release, and Vanda undertakes
no obligation, and specifically declines any obligation, to update
or revise publicly any forward-looking statements, whether as a
result of new information, future events or otherwise.
Corporate Contact:
Jim Kelly
Executive
Vice President and Chief Financial Officer
Vanda Pharmaceuticals Inc.
(202) 734-3428
jim.kelly@vandapharma.com
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