August 4 — Getting too little sleep or not spending enough time in rapid eye movement sleep is associated with being overweight among children and teens, a new U.S. study.

For three consecutive nights, researchers assessed the sleep patterns of 335 youngsters, aged 7 to 17. They looked at total sleep time, time spent in REM, and time it took to fall asleep. Body-mass index was checked at the start of the study, and 45 participants were overweight, while 49 were at risk for becoming overweight.

Compared to normal-weight children, those who were overweight slept about 22 minutes less per night and had lower sleep efficiency , shorter REM sleep, less eye activity during REM sleep, and a longer wait before the first REM period.

After they adjusted for other factors, the researchers concluded that one hour less of total sleep was associated with a twofold increased risk of being overweight. One hour less of REM sleep was associated with a threefold increased risk.

Although the precise mechanisms are currently under investigation, the association between short sleep duration and overweight may be attributed to the interaction of behavioral and biological changes as a result of sleep deprivation, wrote Dr. Xianchen Liu, of the Western Psychiatric Institute and Clinic in Pittsburgh, and colleagues.

They explained that sleep loss causes changes in hormone levels that may affect hunger, and less sleep also means a person has more waking hours in which to eat. Sleep loss also contributes to fatigue the following day, which may lead to less physical activity and fewer calories burned.

Given the fact that the prevalence of overweight among children and adolescents continues to increase and chronic sleep insufficiency becomes more prevalent in modern society, family- and school-based sleep interventions that aim to enhance sleep hygiene and increase sleep duration may have important public health implications for the prevention and intervention of obesity and type 2 diabetes in children, the authors concluded.

“Furthermore, our results demonstrate an important relationship between REM sleep and high BMI and obesity, suggesting that the short sleep-obesity association may be attributed to reduced REM sleep time and decreased activity during REM sleep,” they wrote.

The study was published in the August issue of the Archives of General Psychiatry.

SOURCE: JAMA/Archives journals, news release, Aug. 4, 2008

Moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for all-cause mortality, according to a study in the August 1 issue of the journal Sleep.

Fourteen years after initial data were collected, about 33 percent of participants with moderate to severe sleep apnea had died (six of 18 individuals), compared with 6.5 percent of people with mild OSA (five of 77) and 7.7 percent of people with no OSA (22 of 285). The association between moderate to severe OSA and mortality remained significant after statistical adjustment for other risk factors, producing a fully adjusted hazard ratio of 6.24 for all-cause mortality; mild OSA was not a risk factor for mortality.

“This is the first study to demonstrate an independent association between all-cause mortality and sleep apnea in a community-based study,” said lead author Nathaniel Marshall, PhD, a postdoctoral fellow at the Woolcock Institute of Medical Research in Sydney, Australia. “The size of the increased mortality risk was surprisingly large. In our particular study a six-fold increase means that having significant sleep apnea at age 40 gives you about the same mortality risk as somebody aged 57 who doesn’t have sleep apnea.”

According to Marshall, previous studies that have linked OSA to mortality as an independent risk factor have involved patients referred to sleep clinics rather than community-based samples; the association between OSA and mortality in the community was unknown.

The study involved 380 men and women between the ages of 40 and 65 who were already involved in the Busselton Health Study, an ongoing survey of residents in the rural town of Busselton in the state of Western Australia. From November to December 1990, each participant used a portable home-monitoring device for one night to assess his or her level of sleep-disordered breathing.

Individuals were categorized according to the frequency of recorded respiratory disturbance. Only three participants had severe OSA with an average of 30 or more respiratory disturbances per estimated hour of sleep, while 18 individuals (about 4.7 percent) had moderate to severe OSA with 15 or more respiratory disturbances per hour. Seventy-seven participants (about 20.3 percent) had mild OSA with five to 14 respiratory disturbances per hour, and 285 people (75 percent) had no OSA.

State and national death records were reviewed through 2004 to identify participants who had died and to note the cause of death listed on the death certificates. From the records of the 33 study participants who died, no predominant cause of death could be linked to OSA.

Initial results were adjusted for other mortality risk factors such as age, sex, body mass index, smoking status, blood pressure, cholesterol and diabetes. All statistical models produced a significant relationship between sleep apnea and mortality. No information was gathered about participants’ use of any sleep apnea treatment.

According to Marshall, the results of this study indicate that OSA is a potentially life-threatening condition that demands increased medical attention.

“Our findings, along with those from the Wisconsin Cohort, remove any reasonable doubt that sleep apnea is a fatal disease,” he said. “People who have, or suspect that they have, sleep apnea should consult their physicians about diagnosis and treatment options.”

The study was supported by grants from the Australian National Health and Medical Research Council.

According to the American Academy of Sleep Medicine, most people with OSA snore loudly and frequently, with periods of silence when airflow is reduced or blocked. They then make choking, snorting or gasping sounds when their airway reopens. About 80 percent to 90 percent of adults with OSA remain undiagnosed.

The most common treatment for OSA is continuous positive airway pressure (CPAP) therapy, which provides a steady stream of air through a mask that is worn during sleep. This airflow keeps the airway open to prevent pauses in breathing and restore normal oxygen levels.

A media fact sheet about obstructive sleep apnea is available from the AASM at http://www.aasmnet.org/Resources/FactSheets/SleepApnea.pdf. Information from the AASM for patients and the public is available about OSA at http://www.sleepeducation.com/Disorder.aspx?id=7 and about CPAP at http://www.sleepeducation.com/CPAPCentral/.

Sleep is the official journal of the Associated Professional Sleep Societies, LLC, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

American Academy of Sleep Medicine

The submitted registration application for Sublinox has been accepted by the FDA as complete for substantive review after initial evaluation. Sublinox contains the well-known active substance zolpidem and is based on Orexo’s sublingual technology, involving a rapidly disintegrating tablet placed under the tongue.

Meda AB acquired the exclusive world-wide commercialization rights for Sublinox on April 14, 2008. “This FDA’s acceptance increases the chances for a registration approval during 2009″, said Anders Lonner, CEO of Meda. The data supporting the product includes a clinical study in insomnia patients that was completed in October 2007. That study showed that Sublinox induced sleep 30 percent earlier compared to Ambien and that patients remained asleep throughout the night with comparable safety.

“This is an important first step to get Sublinox out on the world markets”, said Torbj?rn Bjerke, Orexo’s President and CEO.

MEDA AB (publ) is an international specialty pharma company that concentrates on marketing and market-adapted product development. Acquisitions and long-term partnerships are fundamental factors that drive the company’s strategy. Meda is represented by its own organisations in 26 countries and has more than 1 500 employees within marketing and sales. Meda’s products are sold in about 120 countries worldwide. The Meda share is listed under Large Cap on the OMX Nordic Stock Exchange. Find out more, visit http://www.meda.se.

About Orexo

Orexo is a pharmaceutical company, focusing on development of new, patented drugs by combining well-documented substances with innovative technologies, and the development of new treatments for respiratory and inflammatory diseases. Orexo has a broad and competitive late-stage product portfolio, including two marketed products, five products in clinical phase and two undergoing registration. Orexo has head office in Uppsala and is listed on the OMX Nordic Exchange Stockholm, Small Cap (ticker: ORX)

http://www.orexo.com

Neurogen Corporation (Nasdaq: NRGN) announced that, as planned, it commenced a Phase 2/3 clinical trial in chronic insomnia patients with the Company’s insomnia agent, adipiplon and that, based upon reports from initial dosing of a higher than anticipated rate of unwanted next day effects, the Company has suspended dosing in the study. Neurogen believes that the bilayer tablet formulation of adipiplon being used in the study may not be performing as expected.

The Company plans additional investigation of the bilayer tablet before proceeding further. In prior studies Neurogen has simultaneously administered various doses of both immediate release and controlled release forms of adipiplon. The current study is the first trial in which it has used the two forms laminated together into one bilayer tablet. In previous testing in over 600 subjects, adipiplon has been well tolerated.

“We are disappointed by this setback,” said Stephen R. Davis, Neurogen’s President and CEO. “We do not yet know whether there is a path forward with lower doses of the existing formulation or whether further formulation development would be required. Until we further assess the situation and determine whether there is a path forward we can and should take, we will carefully limit our resource commitments to this program. We remain focused on our ongoing Phase 2 studies with our dopamine partial agonist, aplindore, in Parkinson’s disease and in restless legs syndrome,” Mr. Davis continued.

About Neurogen’s Insomnia Program

Adipiplon has been tested in Phase 1 and 2 studies in over 600 subjects for the treatment of insomnia, demonstrating statistical significance compared to placebo on primary endpoints for sleep initiation and maintenance in patients with chronic insomnia. Adipiplon has also demonstrated statistical significance compared to placebo for self-reported quality of sleep in all completed Phase 2 studies to date. Additionally, in studies completed to date it has been well tolerated at all doses tested.

The leading prescription drugs approved for treatment of both onset and maintenance symptoms of insomnia work by modulating the gamma-aminobutyric acid (GABA) system of neurotransmitters. GABA is a chemical naturally released in certain parts of the brain to inhibit brain activity. Adipiplon is a partial agonist which preferentially targets the alpha-3 receptor subtype of the GABA-A neurotransmitter system. Neurogen believes this unique profile may provide a wider therapeutic window than that achieved with other insomnia agents.

Helpful websites for information on insomnia:

National Sleep Foundation
National Institutes of Health

About Neurogen

Neurogen Corporation is a drug development company focusing on small-molecule drugs to improve the lives of patients suffering from disorders with significant unmet medical need, including insomnia, Parkinson’s disease, restless legs syndrome (RLS), anxiety and pain. Neurogen conducts its drug development independently and, when advantageous, collaborates with world-class pharmaceutical companies to access additional resources and expertise.

Safe Harbor Statement

The information in this press release contains certain forward-looking statements, made pursuant to applicable securities laws that involve risks and uncertainties as detailed from time to time in Neurogen’s SEC filings, including its most recent 10-K. Such forward-looking statements relate to events or developments that we expect or anticipate will occur in the future and include, but are not limited to, statements that are not historical facts relating to the timing and occurrence of anticipated clinical trials, and potential collaborations or extensions of existing collaborations. Actual results may differ materially from such forward-looking statements as a result of various factors, including, but not limited to, risks associated with the inherent uncertainty of drug research and development, difficulties or delays in development, testing, regulatory approval, production and marketing of any of the Company’s drug candidates, adverse side effects or inadequate therapeutic efficacy or pharmacokinetic properties of the Company’s drug candidates or other properties of drug candidates which could make them unattractive for commercialization, advancement of competitive products, dependence on corporate partners, the Company’s ability to retain key employees, sufficiency of cash to fund the Company’s planned operations and patent, product liability and third party reimbursement risks associated with the pharmaceutical industry. For such statements, Neurogen claims the protection of applicable laws. Future results may also differ from previously reported results. For example, positive results or safety and tolerability in one clinical study provides no assurance that this will be true in future studies. Neurogen disclaims any intent and does not assume any obligation to update these forward-looking statements, other than as may be required under applicable law.

National Sleep Foundation

July 24 — Researchers report today the identification of a new cog in the machinery of the molecular clock that controls mammalian circadian rhythms.

But the protein, SIRT1, is not merely some new component. It can also sense and act on the cell’s metabolic state. And it is related to genes that have been implicated in longevity. Thus, these findings link for the first time the molecular mechanisms of circadian rhythms, metabolism and longevity in a single protein.

“Everyone feels that their normal life is dominated by circadian rhythms, and they might feel also that metabolism is circadian: hormones, temperature, desire to eat, sleep — all that is metabolism,” explained Paolo Sassone-Corsi of the University of California, Irvine, who led one of the two research teams that reported the findings. “The fact that we have found a molecular link between internal clock and metabolism explains why these are so interconnected.”

The findings “are actually very exciting, because they link the very interesting sirtuin-1 pathway to the circadian clock for the first time,” said Joseph Takahashi, a professor of neurobiology and physiology at Northwestern University, who was not involved in this research. “It is a direct molecular link to the clock mechanism.”

The findings were published in a pair of reports in the July 25 issue of Cell.

Sassone-Corsi and Ueli Schibler, of the University of Geneva, Switzerland, led independent research teams that made the discoveries. Each approached the problem from a different angle.

Sassone-Corsi’s group was looking specifically for an enzyme that could counterbalance the activity of another integral clock component, a protein called CLOCK.

According to Sassone-Corsi, approximately 10 percent to 15 percent of all cellular genes are expressed or regulated in a circadian manner; that is, their abundance or activity fluctuates over the course of the day.

Key to that fluctuation is the so-called molecular clock. At the heart of the clock mechanism are two proteins, CLOCK and BMAL1. These two proteins interact to form a complex that binds to DNA to activate the expression of several other circadian genes, including Period and cryptochrome . It takes a while for PER and CRY proteins to accumulate, but once they do , they form a complex that blocks CLOCK and BMAL1 activity. PER and CRY expression then stops , and the PER and CRY proteins slowly degrade, allowing the clock to reset itself. This entire process occurs over about 24 hours, hence, a circadian rhythm.

Interestingly, CLOCK does more than bind DNA. It also functions as an enzyme that catalyzes the transfer of a small molecular mark to certain proteins, thereby changing their activities, much like flipping a switch. One of those targets is BMAL1.

Sassone-Corsi reasoned that for every enzyme that can add a molecular mark, there must be another that can remove it. “That’s the way biology works; there is yin and yang to any function in the cell,” he said.

His search led him to SIRT1, an enzyme that is responsive to metabolism and that requires, among other things, a molecule called nicotinamide adenine dinucleotide to function. Because NAD levels fluctuate with the cell’s metabolic state, SIRT1 is likewise responsive to metabolism.

“The key finding [for both papers is] that SIRT1 is a deacetylase involved in regulating circadian biology,” said Sassone-Corsi. “And because SIRT1 is regulated by NAD, it links metabolism with circadian rhythms.”

Schibler’s team arrived at the same conclusion from a completely different angle. Recognizing that feeding cycles are critical to synchronizing the molecular clock, Schibler reasoned there must be a clock component capable of sensing metabolic state. As NAD seemed a good candidate for such a sensor, he looked specifically at NAD-binding proteins.

“You need something that senses feeding and metabolism, and there are many [candidates],” Schibler said. “The one we report on in this paper is SIRT1. We believe we have a very good candidate with this SIRT1.”

Together, the two reports demonstrate that SIRT1 activity operates in a circadian manner; that SIRT1 binds directly to CLOCK/BMAL1 in a circadian manner; that SIRT1 deacetylates both BMAL1 and PER2, leading to their degradation and/or loss of activity; and that loss of SIRT1 activity dampens circadian rhythms.

Takahashi noted several interesting aspects to this study. First is the fact that SIRT1 is regulated by NAD.

“There are many deacetylases,” he said. “So, it certainly didn’t have to be SIRT1. The fact that the deacetylase is also regulated by a metabolic indicator is exciting.”

Indeed, Schibler said he suspects, but does not yet know for certain, that NAD levels also fluctuate in a circadian manner.

Also surprising, Takahashi said, is the fact that SIRT1 is an integral component of the clock itself, like a cog in the machinery, rather than some downstream player.

“And then,” he added, “because the SIRT1 pathway itself is so interesting, because of its role in longevity, that suggests a new direct link between the longevity/metabolism pathway and the circadian clock, a direct molecular link that wasn’t known before.”

Takahashi noted this study has potential, albeit very long-term, therapeutic implications.

“If you screw up circadian rhythm enough, you can end up with metabolic disorders,” he said, citing CLOCK-mutant mice which, in addition to having disrupted circadian cycles, are also obese and predisposed to diabetes.

Said Sassone-Corsi, “SIRT1 or CLOCK might make useful drug targets. Not today or tomorrow, but in the future. I have a feeling there will be a lot of interest in these studies once they come out.”

SOURCES: Paolo Sassone-Corsi, Ph.D., chairman, Department of Pharmacology, University of California, Irvine; Ueli Schibler, Ph.D., professor, Molecular Biology, and investigator, National Center of Competence in Research “Frontiers in Genetics,” University of Geneva, Switzerland; Joseph Takahashi, Ph.D., professor, neurobiology and physiology, and investigator, Howard Hughes Medical Institute, Northwestern University, Evanston, Ill.; July 25, 2008, Cell

June 12 — Normal sleep is associated with healthy aging, a new study found.

Researchers at the University of California, San Diego assessed 2,226 women aged 60 and older for use of sleeping aids, daytime sleepiness, napping, insomnia, early morning awakening, snoring, overall sleep quality, and sleep duration. Based on the results, 20.8 percent of the women were categorized as “successful agers.”

Less daytime napping and fewer complaints of insomnia best predicted successful aging, according to the researchers, who found no direct relationship between the use of sleeping aids and successful aging.

Increased severity of sleep disturbances predicted lower self-rated successful aging and a greater difference between perceived and actual age.

“Our findings that reports of better sleep are related to successful aging reinforce the idea that good sleep is of utmost importance for good health. Health care professionals need to ask their patients — of all ages — about sleep and help those with poor sleep to find ways for improvement,” study author Sonia Ancoli-Israel said in a prepared statement.

The study was presented June 11 at the annual meeting of the Associated Professional Sleep Societies, in Baltimore.

Many older adults get less sleep than they need, and one major reason is difficulty falling asleep. Previous research of people over age 65 found that 13 percent of men and 36 percent of women take more than 30 minutes to fall asleep, according to background information in a news release about the study.

Older people often sleep less deeply and wake up more often throughout the night, and they tend to get sleepier earlier in the evening and awaken earlier in the morning than younger people.

Poor sleep can lead to a number of problems such as depressed mood, attention and memory problems, excessive daytime sleepiness, more nighttime falls and increased use of sleep aids. Lack of sleep is also associated with increased risk of health problems such as obesity, cardiovascular disease and diabetes.

SOURCE: American Academy of Sleep Medicine, news release, June 11, 2008

June 11 — Children with bigger necks are more likely to develop a sleep-related breathing disorder, says a University of Virginia study.

Researchers looked at 215 children, aged 18 months to 18 years, who were referred to a pediatric sleep center. Of these children, 37.3 percent were obese and had an increased frequency of snoring.

The children’s neck size, in the sitting and neutral head position, was measured and apena-hypopnea index and mean oxygen saturation values were used as indicators of the severity of the sleep-related breathing disorder.

Age-adjusted neck size correlated with body-mass index and weight and showed a higher correlation with AHI than did BMI, weight or tonsil size. Neck size also showed a strong inverse correlation with mean oxygen saturation and was a better predictor of mean oxygen saturation than BMI, weight or tonsil size, the study found.

“Children with bigger neck sizes for age should be queried about snoring, apnea, excessive sleepiness, and hyperactivity. Neck size should be considered in the clinical evaluation of children with a history of snoring and apnea,” study author Dr. Pearl L. Yu said in a prepared statement.

The findings were expected to be presented at the annual meeting of the Associated Professional Sleep Societies, in Baltimore.

Sleep-related breathing disorders affect breathing during sleep. The most common type is obstructive sleep apnea , which occurs when the tissue in the back of the throat collapses and blocks the airway.

OSA occurs in about 2 percent of young children, according to background information in a news release about the study. OSA can develop in children at any age but is most common in preschoolers, when the tonsils and adenoids are large compared to the throat. OSA is also common obese children.

In early childhood, OSA can slow a child’s growth rate. Untreated OSA can also lead to high blood pressure.

SOURCE: American Academy of Sleep Medicine, news release, June 10, 2008

Vanda Pharmaceuticals Inc. (Nasdaq: VNDA) (Vanda) announced positive top-line results from a Phase III trial showing that its investigational drug candidate, tasimelteon (VEC-162), a novel melatonin agonist, met the primary endpoint of the trial and significantly improved sleep in adult patients with chronic insomnia.

“We are excited that the results of this Phase III chronic insomnia study demonstrate the clinical utility of tasimelteon and the ability of the compound to treat sleep disorders over a period of four weeks. The mechanism of action of tasimelteon as a circadian regulator gives Vanda the opportunity to explore its use for the treatment of circadian rhythm sleep disorders as well as chronic primary insomnia,” stated Paolo Baroldi, MD, PhD, Vanda’s Chief Medical Officer.

This Phase III, multi-center, placebo-controlled, 4-week trial evaluated 322 patients with chronic primary insomnia. Patients were randomized to receive either 20 mg or 50 mg of tasimelteon or placebo over the course of four weeks. The primary endpoint consisted of the evaluation of the immediate and short-term (average of Nights 1 and ability of tasimelteon to improve sleep onset as measured by Latency to Persistent Sleep (LPS) through polysomnography (PSG). Secondary endpoints evaluated tasimelteon’s ability to maintain improvements on sleep onset after long-term (average of Nights 22 and 29) use of the compound as well as measures of sleep duration (Total Sleep Time, TST) and sleep maintenance (Wake After Sleep Onset, WASO). Patients were eligible for the study if symptoms of insomnia were chronic and LPS was greater than 30 minutes.

Significant Improvement in Sleep Onset Sustained through Study Duration

These results demonstrate that tasimelteon was able to improve LPS significantly, and that this effect persisted for the 4 week duration of the study. The results on LPS at night 1 (N1)/night 8 (N8), and night 22 (N22)/night 29 (N29) are as follows.

— Mean LPS at baseline (before drug treatment) was 78.8 minutes in the 20mg group, 76.4 minutes in the 50mg group, and 78.2 minutes in the placebo group. On Nights 1 and 8 of treatment, mean LPS improved by 45.0 minutes in the 20mg group (p<.001), by 46.4 minutes in the 50mg group (p<.001), and by 28.3 minutes in the placebo group. On Nights 22 and 29 of treatment, mean LPS improved by 49.4 minutes in the 20mg group (p<.001), by 45.1 minutes in the 50mg group (p=.016), and by 33.9 minutes in the placebo group. All statistical comparisons are between tasimelteon dose versus placebo.

Importantly, this effect was also seen acutely on the first night of treatment. Patients in the 20mg and 50mg groups fell asleep 22.9 minutes (p<.001) and 25.9 minutes (p<.001) faster, respectively, than those in the placebo group, as measured objectively through PSG. Data from subjective patient self-reports on these nights were consistent with this finding.

Additional Phase III Results on Sleep Maintenance Parameters

The trial also evaluated parameters of sleep maintenance, including TST and WASO.

— Mean TST at baseline (before drug treatment) was 325.7 minutes in the 20mg group, 327.0 minutes in the 50mg group, and 328.9 minutes in the placebo group. On Nights 1 and 8 of treatment, mean TST improved by 51.4 minutes in the 20mg group (p=.089), by 52.0 minutes in the 50mg group (p=.074), and by 40.0 minutes in the placebo group. On Nights 22 and 29 of treatment, mean TST improved by 60.3 minutes in the 20mg group (p=.057), by 48.6 minutes in the 50mg group (not statistically significant, nss), and by 47.4 minutes in the placebo group. All statistical comparisons are between tasimelteon dose versus placebo.

— Mean WASO at baseline (before drug treatment) was 92.6 minutes in the 20mg group, 93.8 minutes in the 50mg group, and 93.8 minutes in the placebo group. On Nights 1 and 8 of treatment, mean WASO improved by 12.2 minutes in the 20mg group (nss), by 14.1 minutes in the 50mg group (nss), and by 11.7 minutes in the placebo group. On Nights 22 and 29 of treatment, mean WASO improved by 17.7 minutes in the 20mg group (nss), by 10.2 minutes in the 50mg group (nss), and by 20.3 minutes in the placebo group. There were no significant differences in this secondary endpoint comparing tasimelteon versus placebo groups.

Analysis of the baseline PSG data revealed that the sleep disruption in this patient population occurred primarily during the first third of the 8-hour night. This is not unexpected given that the entry criteria in the study focused upon recruiting subjects with difficulty falling asleep and that there was no WASO entry criterion. At baseline, sleep efficiency (i.e. the percent of time spent asleep during the time available for sleep) during the first, second and last thirds of the night were 50.7%, 79.4% and 74.5%, respectively. Therefore, Vanda evaluated the effect of tasimelteon on sleep maintenance parameters in the first third of the night, when the sleep disruption was greatest in this population of chronic primary insomnia patients.

— Mean TST during the first third of the night at baseline (before drug treatment) was 79.0 minutes in the 20mg group, 82.3 minutes in the 50mg group, and 82.2 minutes in the placebo group. On Nights 1 and 8 of treatment, mean TST during the first third of the night improved by 40.9 minutes in the 20mg group (p<.001), by 39.4 minutes in the 50mg group (p<.001), and by 26.6 minutes in the placebo group. On Nights 22 and 29 of treatment, mean TST during the first third of the night improved by 45.2 minutes in the 20mg group (p<.001), by 40.1 minutes in the 50mg group (p<.01), and by 30.6 minutes in the placebo group. All statistical comparisons are between tasimelteon dose versus placebo.

— Mean WASO during the first third of the night at baseline (before drug treatment) was 20.8 minutes in the 20mg group, 21.3 minutes in the 50mg group, and 21.3 minutes in the placebo group. On Nights 1 and 8 of treatment, mean WASO during the first third of the night improved by 2.3 minutes in the 20mg group (p<.01), and by 1.8 minutes in the 50mg group (p<.05), but worsened by 3.1 minutes in the placebo group. On Nights 22 and 29 of treatment, mean WASO during the first third of the night improved by 3.1 minutes in the 20mg group (nss), by 1.8 minutes in the 50mg group (nss) and by 0.6 minutes in the placebo group. All statistical comparisons are between tasimelteon dose versus placebo.

These results reveal that tasimelteon was able to achieve a number of statistically significant improvements on sleep maintenance parameters during the portion of the night in which the patient population studied suffered the greatest impairment. These data are consistent with data from the prior Phase III study (VP-VEC-162-3101), in which 20mg and 50mg of tasimelteon significantly improved LPS (by 21.5 to 26.3 minutes compared to placebo), WASO (by 24.7 to 33.7 minutes compared to placebo), and TST (by 33.7 to 47.9 minutes compared to placebo) in a model of transient insomnia. Taken together, the results of both of these studies demonstrate the versatility of tasimelteon to treat the symptoms of insomnia acutely and chronically both in a model of transient insomnia and in patients with chronic primary insomnia.

“These results suggest that circadian misalignment may play an important role in the pathophysiology of chronic primary insomnia in many patients, especially those who have difficulty falling asleep,” said Charles A. Czeisler, PhD, MD, FRCP, Chairman of Vanda’s Scientific Advisory Board.

This study also demonstrated that tasimelteon was well-tolerated and exhibited a safety profile generally similar to placebo.

About Tasimelteon

Tasimelteon, (VEC-162), is Vanda’s novel melatonin agonist in development for the treatment of insomnia and circadian rhythm sleep disorders (CRSD). Researchers believe that the interplay between the MT-1 and MT-2 pathways and environmental signals such as external light-dark cues results in the drive for wakefulness during daytime hours and sleepiness during night-time hours.(1) In patients with insomnia or CRSD, the regulation of the sleep/wake cycle is disrupted.(2) By binding to both the MT-1 and MT-2 receptors in a balanced fashion, tasimelteon helps modulate the patient’s circadian rhythm, re-setting the sleep/wake cycle and providing simultaneous, immediate sleep- promoting benefits.(1)

About Insomnia and Circadian Rhythm Sleep Disorders

Insomnia, the most common sleep disorder, affects approximately 50-70 million American adults.(3,4) It is characterized by difficulty falling asleep, waking frequently during the night, waking too early and not being able to return to sleep, or waking up and not feeling refreshed.(5)

CRSD, another type of sleep disorder defined as the inability to sleep at usual or customary times, affects millions of Americans in a number of forms, including Shift Work Disorder, which affects 10% of Americans who are shift workers; Delayed Sleep Phase Disorder, which affects 5-10% of chronic insomnia patients; and Jet Lag Disorder, which typically affects air travelers crossing five or more time zones.(6-8)

About Vanda Pharmaceuticals Inc.

Vanda Pharmaceuticals Inc. is a biopharmaceutical company focused on the development and commercialization of clinical-stage product candidates for central nervous system disorders. The company has three product candidates. Vanda’s lead product candidate, iloperidone, is a compound for the treatment of schizophrenia for which Vanda submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in September 2007. The FDA accepted Vanda’s iloperidone NDA for filing in November 2007 and Vanda expects a decision from the FDA on or about July 27, 2008. Vanda’s second product candidate, tasimelteon (VEC-162), is a compound for the treatment of sleep and mood disorders, which is currently in Phase III for chronic primary insomnia. Vanda’s third product candidate, VSF-173, is a compound for the treatment of excessive sleepiness in Phase II. 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,” “targets,” “likely,” “will,” “would,” and “could,” 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. Vanda is at an early stage of development and may not ever have any products that generate significant revenue. Important factors that could cause actual results to differ materially from those reflected in the company’s forward-looking statements include, among others: delays in the completion of Vanda’s clinical trials; a failure of Vanda’s product candidates to be demonstrably safe and effective; Vanda’s failure to obtain regulatory approval for its products or to comply with ongoing regulatory requirements; a lack of acceptance of Vanda’s product candidates in the marketplace, or a failure to become or remain profitable; Vanda’s inability to obtain the capital necessary to fund its research and development activities; Vanda’s failure to identify or obtain rights to new product candidates; Vanda’s failure to develop or obtain sales, marketing and distribution resources and expertise or to otherwise manage its growth; a loss of any of Vanda’s key scientists or management personnel; losses incurred from product liability claims made against Vanda; a loss of rights to develop and commercialize Vanda’s products under its license and sublicense agreements and other factors that are described in the “Risk Factors” section (Part II, Item 1A) of Vanda’s quarterly report on Form 10-Q for the quarter ended March 31, 2008 (File No. 000-51863). In addition to the risks described above and in Part II, Item 1A of Vanda’s quarterly report 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.

References:

1. Doghramji K. Melatonin and its receptors: a new class of sleep-promoting agents. J Clin Sleep Med. 2007;3:S17-S23.

2. Rajput V, Bromley SM. Chronic insomnia: a practical review. AAFP. 1999;60:1431-1438.

3. National Sleep Foundation. Most Common Sleep Problems in Women.

4. Centers for Disease Control and Prevention. Perceived Insufficient Rest or Sleep - Four States, 2007. MMWR. 2008;57:200-203.

5. National Institutes of Health. NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. Available at: http://consensus.nih.gov/2007/2007InsomniaSOS026html.htm. Accessed on June 18, 2008.

6. D’Alonzo GE, Krachman SL. Circadian rhythm sleep disorders. JAOA. 2000;100(8):S15-21.

7. Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T. Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers. Sleep. 2004;27:1453-62.

8. Carney PR, Berry RB, Geyer JD, eds. Clinical Sleep Disorders. Lippincott Williams & Wilkins, 2004.

Vanda Pharmaceuticals Inc.
http://www.vandapharma.com

Covidien (NYSE: COV, BSX: COV), a leading global healthcare products company, announced the latest advance in its “Unite to Treat Sleep Apnea” initiative, an integrated program connecting physicians, sleep labs, treatment providers and patients to improve the diagnosis and treatment of those afflicted with obstructive sleep apnea. The Company is now partnering with Sleep Pointe, an organization dedicated to providing sleep apnea management and wellness programs within the transportation industry.

Covidien created the “Unite to Treat Sleep Apnea” initiative in response to the increased demand for sleep apnea treatment. According to the National Institutes of Health, approximately 12 million Americans suffer from sleep apnea, and an additional 10 million remain undiagnosed.

“Undiagnosed and untreated sleep apnea is an urgent issue, as it reduces productivity and shortens life spans. This partnership is designed to help keep drivers in the transportation industry safe by increasing the availability of diagnostic and therapeutic resources,” said Scott Drake, President, Respiratory and Monitoring Solutions, Covidien. “Initiatives like ‘Unite to Treat Sleep Apnea’ are valuable because they further the diagnosis, treatment and compliance of this life-threatening disease.”

The transportation industry is directly impacted by the serious potential consequences of drivers affected by untreated or undiagnosed sleep apnea. Approximately 28% of commercial truck drivers are affected by sleep apnea1, and without treatment, they are up to seven times more likely to be involved in an accident2. Proper treatment of sleep apnea may help reduce the risk of many other associated diseases, including hypertension, diabetes and cardiovascular disease.

“Professional drivers are a difficult group of patients to reach,” said Dr. Neale Lange, MD, FCCP, FASM, director of Sleep Services at St. Anthony Central Hospital, Denver. “Any intervention that removes or reduces barriers to diagnosis and treatment of sleep apnea in anyone operating a vehicle should be strongly supported. It’s not only about sleep quantity but also about sleep quality. Focusing on sleep as it relates to health should become a priority of our healthcare system.”

Using Covidien’s broad range of sleep products, Sleep Pointe has developed a comprehensive sleep management program dedicated exclusively to the health and safety of those in the transportation industry. Sleep Pointe’s Mobile Sleep Solution Centers are built on 53-foot trailers, feature private bedrooms, bathrooms and a fully functional sleep technician room and will be available at many easily accessible locations across the country.

“Untreated sleep apnea in the transportation industry is known to contribute to serious accidents and severe health consequences,” said Duke Naipohn, President and CEO, Sleep Pointe. “This alliance will help Sleep Pointe accomplish our mission of keeping drivers on the road, improving their health and wellness and reducing the incidence of fatigue-related accidents.”

An inaugural event was held today at Covidien’s Boulder, Colorado, campus to formally announce this partnership.

Covidien plans to expand its “Unite to Treat Sleep Apnea” initiative globally to support comprehensive solutions that better enhance diagnosis, treatment and compliance in the rapidly growing sleep care industry. For more information about the “Unite to Treat Sleep Apnea” program, please visit www.covidien.com/sleepapnea.

About Covidien

Covidien is a leading global healthcare products company that creates innovative medical solutions for better patient outcomes and delivers value through clinical leadership and excellence. Covidien manufactures, distributes and services a diverse range of industry-leading product lines in four segments: Medical Devices, Imaging Solutions, Pharmaceutical Products and Medical Supplies. With 2007 revenue of nearly $9 billion, Covidien has more than 42,000 employees worldwide in 57 countries, and its products are sold in over 130 countries. Please visit www.covidien.com to learn more about our business.

About Sleep Pointe

Sleep Pointe is a sister company of Somnograph Inc., a privately-held sleep diagnostic company headquartered in Wichita, KS. Somnograph has performed well over 100,000 sleep studies in its ten years of existence. Sleep Pointe intends to use this experience and expertise to provide obstructive sleep apnea education, screening, testing, and treatment for transportation companies throughout the U.S. To learn more, please visit http://www.sleeppointe.com.

Covidien Contacts

1 Pack, Allen I; Dinges, David F.; Maislin, Greg. A Study of Prevalence of Sleep Apnea Among Commercial Truck Drivers, FMCSA, Publication No. DOT-RT-02-030, Washington, DC, 20002.

2 Horstmann, S.; Hess, C.; Bassett, C.; Gusser, M.; and Mathis, J. (2000). Sleepiness-Related Accidents in Sleep Apnea Patients. Sleep, 23 (3), 383-389.

http://www.covidien.com

More than half of all older adults complain about having difficulties sleeping. Most don’t bother seeking treatment. Those who do usually turn either to medications, which can lead to other health problems, or behavior therapies, which are costly and often not available close to home.

Now, UCLA researchers report that practicing tai chi chih, the Westernized version of a 2,000-year-old Chinese martial art, promotes sleep quality in older adults with moderate sleep complaints. The study, which will be published in the journal Sleep, is currently available in the journal’s online edition.

In the study, 112 healthy adults ranging in age from 59 to 86 were randomly assigned to one of two groups for a 25-week period: The first group practiced 20 simple tai chi chih moves; the other participated in health education classes that included advice on stress management, diet and sleep habits.

At the beginning of the study, participants were asked to rate their sleep based on the Pittsburgh Sleep Quality Index, a self-rated questionnaire that assesses sleep quality, duration and disturbances over a one-month time interval.

The study found that the tai chi chih group showed improved sleep quality and a remission of clinical impairments, such as drowsiness during the day and inability to concentrate, compared with those receiving health education. The tai chi chih participants showed improvements in their own self-rating of sleep quality, sleep duration and sleep disturbance.

“Poor sleeping constitutes one of the most common difficulties facing older adults,” said lead study author Dr. Michael Irwin, the Norman Cousins Professor of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine at UCLA and director of the UCLA Cousins Center for Psychoneuroimmunology.

Irwin noted that 58 percent of adults age 59 and older report having difficulty sleeping at least a few nights each week. However, sleep problems remain untreated in up to 85 percent of people. And for those who do seek help, the usual remedy is a sedative.

But sedatives can cause side effects, according to Irwin.

“It’s not uncommon for older adults to experience daytime confusion, drowsiness, falls and fractures, and adverse interactions with other medications they may be taking,” he said.

And while most health professionals generally agree that physical exercise enhances sleep quality, given the physical limitations of the elderly, rigorous exercise might not be an option. That’s why tai chi chih, with its gentle, slow movements, is an attractive exercise option for the elderly population.

“It’s a form of exercise virtually every elderly person can do, and this study provides more across-the-board evidence of its health benefits,” Irwin said.

The research piggybacked on a study published in April 2007 by Irwin that showed tai chi chih boosted the immune system of elderly people suffering from shingles.

Other studies done at UCLA have shown that tai chi chih can help people who suffer from tension headaches and have suggested that it may aid in decreasing high blood pressure.

The UCLA Cousins Center for Psychoneuroimmunology encompasses an interdisciplinary network of scientists working to advance the understanding of psychoneuroimmunology by linking basic and clinical research programs and by translating findings into clinical practice. The center is affiliated with the Semel Institute for Neuroscience and Human Behavior and the David Geffen School of Medicine at UCLA.

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