[Nfbf-l] {Spam?} Tasimelteon Restores Daily Cortisol Rhythms in Blind Patients with Non-24-Hour Disorder

[Alan Dicey]

Dear Friends,
Found this in my In Box, and I am passing it along to you.
With Best Regards,
Alan
Miami, Florida

----- Original Message ----- 
From: Vanda Pharmaceuticals News
To: adicey at bellsouth.net
Sent: Monday, October 15, 2012 7:09 AM
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.


References

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.

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 
(MDD).

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/.


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 extent and effectiveness of the development, sales and marketing and 
distribution support Fanapt® receives; Vanda's ability to successfully 
commercialize Fanapt® 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, 
product candidates or partnered products or to comply with ongoing 
regulatory requirements; a lack of acceptance of Vanda's products, product 
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 
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a loss of rights to develop and commercialize Vanda's products or product 
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. 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