[Nfbk] FW: Tasimelteon Restores Daily Cortisol Rhythms in Blind Patients with Non-24-Hour Disorder

George Stokes kd4ckt at bellsouth.net
Mon Oct 15 12:13:33 UTC 2012



From: Vanda Pharmaceuticals News [mailto:news at vandapharma.com] 
Sent: Monday, October 15, 2012 7:18 AM
To: george.stokes at nfbky.org
Subject: Tasimelteon Restores Daily Cortisol Rhythms in Blind Patients with
Non-24-Hour Disorder


Tasimelteon Restores Daily Cortisol Rhythms in Blind Patients with
Non-24-Hour Disorder

WASHINGTON, D.C. October 15 2012, /PRNewswire/--  Vanda Pharmaceuticals
(NASDAQ:VNDA), a biopharmaceutical company focused on the development and
commercialization of products for the treatment of central nervous system
disorders, reported today that tasimelteon has been shown for the first time
to restore daily cortisol rhythms in totally blind patients suffering from
Non-24-Hour Disorder (Non-24).  Tasimelteon was previously reported to
entrain the 24-hour rhythm of melatonin secretion in patients with Non-24.
Cortisol is a key regulatory hormone which exhibits a circadian rhythm,
rising in the early morning and falling in the evening.  The circadian
regulation of the cortisol rhythm is necessary for the human body to be
prepared for a wide range of daily activities and physiologic functions,
including blood pressure variation, utilization of fatty acids, circulating
lymphocytes and immunity.  A growing body of data suggests that
tasimelteon's entraining effects are accomplished through a direct resetting
of the master body clock, located in the suprachiasmatic nucleus (SCN) of
the hypothalamus.    Tasimelteon is a circadian regulator in development for
the treatment of Non-24 in totally blind individuals. 

"It is particularly noteworthy that tasimelteon can entrain the diurnal
cortisol rhythm," said Dr. Fred Turek, Director of the Center for Sleep &
Circadian Biology at Northwestern University, "because it is an endocrine
rhythm that is tightly regulated by the master clock in the SCN, indicating
that tasimelteon is acting on the central circadian clock in humans."

"We have confirmed that the circadian dyssynchrony seen in Non-24 extends
beyond the melatonin rhythm and the sleep-wake cycle and into the
dyssynchrony of the fundamental diurnal variation of endocrine system
function as exemplified by the circadian rhythm of cortisol," said Mihael H.
Polymeropoulos, MD, President and CEO of Vanda.  "Tasimelteon's effect on
both melatonin and cortisol rhythms further confirms its potential to reset
the master body clock and address the circadian dyssynchrony which is
inherent in Non-24." 

This observation was made during an open-label segment of Vanda's RESET
study.   RESET is a Phase III study of the maintenance effect of tasimelteon
in the treatment of Non-24.  Totally blind patients with Non-24 were given a
20mg dose of tasimelteon daily at bed time for 6 weeks. The rhythms of
melatonin and cortisol were assessed longitudinally in urine samples.
Entrainment of the cortisol rhythm by tasimelteon was directly associated
with entrainment of the melatonin rhythm in the same patients.  Vanda
believes that the simultaneous entrainment of both melatonin and cortisol
suggests that tasimelteon can reset the master body clock in the SCN through
binding to MT1 and MT2 melatonin receptors.  Tasimelteon's unique balanced
melatonin receptor binding profile may make it well-suited to perform as a
circadian regulator.

The master body clock controls the timing of many aspects of physiology,
behavior and metabolism that show daily rhythms, including the sleep-wake
cycles, body temperature, alertness and performance, metabolic rhythms and
certain hormones which exhibit circadian variation. Outputs from the SCN
control many endocrine rhythms including those of melatonin secretion by the
pineal gland as well as the control of cortisol secretion via effects on the
hypothalamus, the pituitary and the adrenal glands. This master body clock,
located in the SCN, spontaneously generates rhythms of approximately 24.5
hours.  These non-24-hour rhythms are synchronized each day to the 24-hour
day-night  cycle by light, the primary environmental time cue which is
detected by specialized cells in the retina and transmitted to the SCN via
the retino-hypothalamic tract.  Inability to detect this light signal, as
occurs in most totally blind individuals, leads to the inability of the
master body clock to be reset daily and maintain entrainment to a 24-hour
day.   This newly reported observation of tasimelteon's ability to restore
cortisol rhythms in patients with Non-24 opens new avenues of inquiry and
discovery in the field of circadian rhythm disorders.


Cui, He, Akira Kohsaka, Hidefumi Waki, Mohammad E. R. Bhuiyan, Sabine S.
Gouraud, and Masanobu Maeda. "Metabolic Cycles Are Linked to the
Cardiovascular Diurnal Rhythm in Rats with Essential Hypertension." PLoS ONE
E17339 6.2 (2011): 1-13. 

Fu, Loning, and Cheng C. Lee. "The Circadian Clock: Pacemaker and Tumour
Suppressor." Nature Reviews 3 (2003): 350-61. 

Young, M., and M. Bray. "Potential Role for Peripheral Circadian Clock
Dyssynchrony in the Pathogenesis of Cardiovascular Dysfunction." Sleep
Medicine 8.6 (2007): 656-67. 

About Non-24-Hour Disorder

Non-24-Hour Disorder is a chronic circadian rhythm disorder that affects
more than 50 percent of the totally blind individuals in the U.S., or 65,000
to 95,000 people.  Non-24 occurs almost entirely in individuals who are
totally blind and lack the light sensitivity necessary to reset the
circadian clock.  Without light perception, the brain's circadian rhythms
which guide many of the body's functions, including sleep, hormone rhythms
and metabolism are not reset to a regular 24-hour cycle.  

Individuals with Non-24 are unable to synchronize their internal clock to
the 24-hour day-night cycle, which disrupts their sleep-wake cycle.  For
more information, please visit http://24sleepwake.com
<http://lnk.ie/ACND/e=george.stokes@nfbky.org/http:/24sleepwake.com/> .

About Tasimelteon

Tasimelteon, an MT1 and MT2 agonist is currently being tested in two Phase
III efficacy studies (SET and RESET) for the treatment of Non-24 in totally
blind patients.  Vanda expects to report top-line results from the SET study
by year end 2012.  Top-line results from the RESET study are expected in the
first quarter of 2013.   These studies will inform a New Drug Application
(NDA) with the US Food and Drug Administration (FDA), which is expected to
be submitted in mid-2013.

Tasimelteon is being studied in both Non-24 and Major Depressive Disorder

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 Pharmaceuticals Inc., please
visit http://www.vandapharma.com/
<http://lnk.ie/ACNE/e=george.stokes@nfbky.org/http:/www.vandapharma.com/> . 


Various statements in this release are "forward-looking statements" under
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similar expressions or words, identify forward-looking statements.
Forward-looking statements are based upon current expectations that involve
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commercialize FanaptR outside of the U.S. and Canada; delays in the
completion of Vanda's clinical trials; a failure of Vanda's products,
product candidates or partnered products to be demonstrably safe and
effective; Vanda's failure to obtain regulatory approval for its products,
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candidates or partnered products in the marketplace, or a failure to become
or remain profitable; Vanda's expectations regarding trends with respect to
its costs and expenses; Vanda's inability to obtain the capital necessary to
fund additional research and development activities; Vanda's failure to
identify or obtain rights to new products or product candidates; Vanda's
failure to develop or obtain sales, marketing and distribution resources and
expertise or to otherwise manage its growth; limitations on Vanda's ability
to utilize some or all of its prior net operating losses and research and
development credits; a loss of any of Vanda's key scientists or management
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candidates under its license and sublicense agreements 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 <http://lnk.ie/ACNF/e=george.stokes@nfbky.org/http:/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. 

Investor/Media Contact: 
Cristina Murphy
Senior Communications Manager 
Vanda Pharmaceuticals Inc. 
(202) 734-3400
cristina.murphy at vandapharma.com 

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