Vanda Announces Positive Phase III Results For Tasimelteon In The
Treatment Of Non-24-Hour Disorder
WASHINGTON, Dec. 18, 2012 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (NASDAQ:VNDA) today announced positive results
from the SET (Safety and Efficacy of Tasimelteon) Phase III study,
evaluating tasimelteon, a circadian regulator for the treatment of
Non-24-Hour Disorder (Non-24). Tasimelteon succeeded in the
primary endpoint of Entrainment of the melatonin (aMT6s) rhythm as
compared to placebo.
Additionally, tasimelteon demonstrated significant improvements
across a number of sleep and wake parameters including measures of
total sleep time, nap duration, and timing of sleep.
Tasimelteon also showed significant improvements over placebo in
the Non-24 Clinical Response Scale (N24CRS) as well as in the
Clinical Global Impression of Change (CGI-C), an overall global
functioning scale. These results provide robust evidence of a
direct and clinically meaningful benefit to patients with
Non-24.
Non-24 is a serious, rare circadian rhythm disorder that affects
a majority of totally blind individuals who lack light perception
and cannot entrain (reset) their master body clock to the 24-hour
day. Currently there is no approved treatment for Non-24.
"Today's results confirm tasimelteon as a strong circadian
regulator capable of entraining the master body clock in patients
with Non-24. We are particularly impressed and excited by the
magnitude and robustness of the direct clinical benefits to
patients," said Mihael H.
Polymeropoulos, M.D., President and CEO of Vanda. "We
believe that tasimelteon can be an effective and clinically
meaningful treatment for patients suffering with this debilitating
disorder."
"As a person who regularly experiences the debilitating symptoms
of Non-24, these findings are important to me and I think they are
important to the blind community as a whole, because they give us
hope that a potential new treatment approach is on the horizon,"
said Melanie Brunson, Executive
Director of the American Council of the Blind.
Primary Endpoints
The SET study was an 84 patient randomized, double-masked,
placebo-controlled study in patients with Non-24. The primary
endpoints for this study were Entrainment of the melatonin (aMT6s)
rhythm to the 24-hour clock and Clinical Response as measured by
Entrainment plus a score of greater than or equal to 3 on
N24CRS.
Primary Endpoint Results
Table 1
|
Tasimelteon (%)
|
Placebo
(%)
|
p-value
|
Entrainment (aMT6s)
|
20.0
|
2.6
|
0.0171
|
Clinical
Response
(Entrainment1+ N24CRS
>=3)
|
23.7
|
0.0
|
0.0028
|
Clinical
Response2
(Entrainment1+
N24CRS >=2)
|
28.9
|
0.0
|
0.0006
|
N24CRS
>=32
|
28.9
|
2.9
|
0.0031
|
N24CRS
>=22
|
57.9
|
20.6
|
0.0014
|
1)
Entrainment status from the randomized portion of the SET study
and/or the screening portion of the RESET study
|
2)
Sensitivity Analysis
|
Secondary Endpoints
The SET study also assessed a number of secondary endpoints
including Entrainment of cortisol rhythm and a broad range of
clinical sleep and wake parameters. These parameters included
improvement in the total nighttime sleep in the worst 25% of nights
(LQ-nTST), decrease in the total daytime sleep duration in the
worst 25% of days (UQ-dTSD) and midpoint of sleep timing (MoST)
which is derived from a combination of the sleep reported for both
nighttime and daytime. CGI-C is a seven-point rating scale of
global functioning with lower scores indicating larger
improvements.
Secondary Endpoint Results
Table 2
|
Tasimelteon
|
Placebo
|
p-value
|
Entrainment (cortisol) (%)
|
17.5
|
2.6
|
0.0313
|
N24CRS (LS mean)
|
1.77
|
0.67
|
0.0004
|
CGI-C1 (LS mean)
|
2.6
|
3.4
|
0.0093
|
LQ-nTST
and UQ-dTSD >=90 min2 (%)
|
23.8
|
4.5
|
0.0767
|
LQ-nTST
and UQ-dTSD >= 45 min3(%)
|
31.6
|
8.8
|
0.0177
|
LQ-nTST (LS mean minutes)
|
57.0
|
16.8
|
0.0055
|
UQ-dTSD1 (LS mean
minutes)
|
-46.2
|
-18.0
|
0.0050
|
MoST (LS mean minutes)
|
34.8
|
14.4
|
0.0123
|
1) For
CGI-C and UQ-dTSD smaller numbers indicate improvement.
|
2) For
this endpoint, only subjects with significant sleep and nap
problems at baseline were included.
|
3)
Sensitivity Analysis
|
The results of the SET study represent the initial data from the
tasimelteon Non-24 Phase III development program and demonstrate
the multiple benefits of this novel therapy in treating patients
suffering from this rare circadian rhythm disorder. In the
SET study, tasimelteon was demonstrated to be safe and well
tolerated. Vanda expects to report top-line results from the
second Phase III study (RESET) for tasimelteon in Non-24 in the
first quarter of 2013. Vanda plans to submit a New Drug
Application (NDA) to the U.S. Food and Drug Administration (FDA) in
mid-2013.
"We would like to thank our patients, their advocates,
investigators, advisors and colleagues for making this study
possible," said Mihael H.
Polymeropoulos, M.D., President and CEO of Vanda. "We
look forward to the successful completion of the Non-24 clinical
program."
Non-24 Scale of Clinical Response (N24CRS)
Assessment
|
Threshold
of response
|
LQ-nTST
|
>=45
minutes increase in average nighttime sleep duration
|
UQ-dTSD
|
>=45
minutes decrease in average daytime sleep duration
|
MoST
|
>=30
minutes increase and a standard deviation <=2 hours during
double-masked phase
|
CGI-C
|
<=2.0
from the average of Day 112 and Day 183 compared to
baseline
|
Tasimelteon Development Program for Non-24
The SET study is the first of four clinical studies conducted as
part of Vanda's Phase III development program for tasimelteon in
the treatment of Non-24. Data from the RESET study, a Phase
III study evaluating the maintenance of entrainment effect of
tasimelteon, is expected in the first quarter of 2013. In
addition, two safety studies are ongoing to support an NDA filing
in the U.S. The tasimelteon Non-24 development program is the
largest conducted to date for any investigational therapy for the
treatment of Non-24.
About Non-24-Hour Disorder
Non-24-Hour Disorder (Non-24) is a serious, rare and chronic
circadian rhythm disorder that affects a majority of totally blind
individuals in the U.S., or between 65,000 and 95,000 people.
Tasimelteon has been granted orphan drug designation for the
treatment of Non-24 in both the U.S. and the European Union.
Non-24 occurs almost entirely in individuals who lack the light
sensitivity necessary to entrain, or synchronize, the master body
clock in the brain with the 24-hour day-night cycle. Most
people have a master body clock that naturally runs longer than
24-hours, and light is the primary environmental cue that resets it
to 24-hours each day. Non-24 sufferers have a master body
clock that continually delays, putting them to sleep later and
later each day, turning night into day and day into night, until
the cycle starts all over again. The sleep condition is
highly disruptive, making it difficult to do well in school, hold
down a job or maintain relationships. For more information on
Non-24, please visit http://24sleepwake.com/.
About Tasimelteon
Tasimelteon is a circadian regulator in development for the
treatment of Non-24. Tasimelteon is a melatonin agonist of the
human MT1 and MT2 receptors, with a 2-4 times greater specificity
for MT2. Tasimelteon's ability to reset the master body clock
in the suprachiasmatic nucleus (SCN), located in the hypothalamus,
results in the entrainment of the body's melatonin and cortisol
rhythms to align to the 24-hour day-night cycle. Tasimelteon
is currently in development for both Non-24 and Major Depressive
Disorder (MDD).
Conference Call
Vanda has scheduled a conference call
for today, Tuesday, December 18, 2012
at 9 AM ET to discuss the trial
results. Investors can call 1-800-901-5231 (domestic) and
1-617-786-2961 (international) and use passcode
51793839. A replay of the call will be available
beginning Tuesday, December 18, 2012,
at 11:00 AM ET and will be accessible
until Tuesday, December 25, 2012, at
12:00 PM ET. The replay
call-in number is 1-888-286-8010 for domestic callers and
1-617-801-6888 for international callers. The access
number is 17591426.
The conference call will be broadcast simultaneously on Vanda's
website, http://www.vandapharma.com. 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. The call will also be archived on
Vanda's website for a period of 30 days, through January 17, 2013.
About Vanda Pharmaceuticals Inc.:
Vanda
Pharmaceuticals Inc. is a biopharmaceutical company focused on the
development and commercialization of products for the treatment of
central nervous system disorders. For more on Vanda, please
visit http://www.vandapharma.com.
Company Contact:
Jim
Kelly
Senior Vice President and Chief Financial Officer
Vanda Pharmaceuticals Inc.
(202) 734-3428
jim.kelly@vandapharma.com
Media Contact:
Kristie
Kuhl
Senior Vice President
Makovsky & Company, Inc.
(212)-508-9642
kkuhl@makovsky.com
CAUTIONARY NOTE REGARDING FORWARD-LOOKING
STATEMENTS
Various statements in this release are
"forward-looking statements" under the securities laws. Words such
as, but not limited to, "believe," "expect," "anticipate,"
"estimate," "intend," "plan," "project," "target," "goal,"
"likely," "will," "would," and "could," or the negative of these
terms and similar expressions or words, identify forward-looking
statements. 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 the
company's forward-looking statements include, among others: the
inability to reach agreement with the FDA regarding Vanda's
regulatory approval strategy or proposed path to approval for
tasimelteon for the treatment of Non-24-Hour Disorder; the failure
of Vanda's clinical trials to demonstrate the safety and/or
efficacy of tasimelteon in the treatment of Non-24-Hour Disorder or
Major Depressive Disorder; Vanda's failure to obtain regulatory
approval for tasimelteon for the treatment of Non-24-Hour Disorder
or to comply with ongoing regulatory requirements; delays in the
completion of Vanda's RESET clinical trial for tasimelteon; 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,
2011 which is on file with the 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.
SOURCE Vanda Pharmaceuticals Inc.