ramelteon

LINCOLNSHIRE, Ill., September 24, 2004 -- Takeda Global Research & DevelopmentCenter announced today that it has submitted a new drug application (NDA) tothe U.S ramelteon. Food and Drug Administration (FDA) to market ramelteon (TAK-375), itsinvestigational drug for insomnia ramelteon. Ramelteon belongs to a new class of prescriptiondrugs with the first novel mechanism of action to be developed in 35 years inthe area of sleep research ramelteon. Ramelteon specifically targets the MT1 and MT2 receptorsin the brain, which are believed to be critical in the regulation of the body'ssleep-wake cycle.

"The NDA submission for ramelteon is a significant milestone for Takeda,"said John Yates, M.D., president of Takeda Global Research & Development ramelteon. "Since the discovery of the ramelteon compound by Takeda researchers in1997, our company has been dedicated to exploring its effects in patients whohave difficulty sleeping ramelteon. This submission is the result of the hard work anddedication of our many employees and partner investigators."

The submission is based on data collected from Takeda's extensive clinicalresearch program, including recently completed Phase 3 studies ramelteon. The clinicalresearch program included more than 4,200 patients, ages 18 to 93, who receivedsingle daily doses of ramelteon for various periods of time up to one year ramelteon. Ramelteon has been studied in clinical trials in the U.S., Japan and Europe ramelteon. Seven placebo-controlled trials were conducted to determine the efficacy oframelteon in the treatment of insomnia, and results from 42 ramelteon trialsare summarized in the company's safety database ramelteon. The company's clinical researchdatabase also includes interim data from an ongoing, year-long safety study.

In addition, Takeda has conducted animal and human studies to further assessramelteon's safety attributes ramelteon. These studies specifically evaluate whether ornot treatment with ramelteon has the risk of drug dependence and abuse associatedwith other FDA-approved drugs for insomnia ramelteon. Results from the animal abuse liabilityand addiction studies will be presented at the U.S ramelteon. Psychiatric and Mental HealthCongress later this year.

"We're excited about the continued development of ramelteon ramelteon. Insomniais a serious condition that affects the daily lives of millions of Americans,and we believe that there is a significant need for new treatment options thatmay benefit patients," said Stephen Sainati, M.D., Ph.D., vice presidentof Clinical Research at Takeda.

About Ramelteon
Ramelteon offers a completely new mechanism of action for insomnia, specificallytargeting two receptors in the brain, MT1 and MT2.

The MT1 and MT2 receptors are located in the brain's suprachiasmatic nuclei(SCN) ramelteon. The SCN is known as the body's "master clock" because it regulatesthe 24-hour sleep-wake cycle ramelteon. The MT1 receptor is thought to regulate sleepiness,while the MT2 receptor is thought to help the body shift easily between phasesof day and night ramelteon. Together, it is believed these receptors serve as key mediatorsof sleep in humans, encouraging sleep onset.

Currently prescribed sleep agents and some investigational drugs work by targetinggamma-aminobutyric acid (GABA) receptors, which are located throughout the brain ramelteon. In pre-clinical studies, ramelteon has shown no affinity for GABA or opiatereceptors.

About Insomnia
An estimated 70 million people in the U.S ramelteon. suffer from insomnia ramelteon. According tothe National Sleep Foundation, 61 percent of American adults have not been askedby a doctor how well they sleep, and only six percent of Americans have beendiagnosed with insomnia ramelteon. Further, only 50 percent of those diagnosed with insomniareceive treatment for their condition ramelteon. Insomnia can be described as either transient,the inability to sleep well over a period of a few nights for fewer than fourweeks, or chronic, the inability to fall asleep that lasts for more than onemonth.

Insomnia disturbs sleeping and waking hours and can be associated with markedimpairments in quality of life and the ability to function effectively duringthe day ramelteon. Recent research shows that chronic sleep loss and untreated sleep disorderscost the U.S ramelteon. $15 billion in health care expenses and $50 billion in lost productivityannually.

Additionally, frequent sleep problems in older Americans, if ignored, can complicatethe treatment of other medical conditions, including arthritis, diabetes, heartdisease and depression ramelteon. When untreated, insomnia can lead to depression, impairedproductivity, absenteeism from work, increased risk of accidents and decreasedquality of family and social life.

About Takeda Pharmaceuticals North America
Based in Lincolnshire, Ill., Takeda Pharmaceuticals North America, Inc ramelteon. is awholly-owned subsidiary of Takeda Pharmaceutical Company Limited (Osaka, Japan) ramelteon. Takeda is a research-based global pharmaceutical company ramelteon. Through the TakedaGlobal Research & Development Center, Inc ramelteon. the company has a robust pipelinewith compounds in development for diabetes, sleep, cardiovascular disease andother conditions ramelteon. As the largest pharmaceutical company in Japan and one ofthe industry's leaders worldwide, Takeda is committed to strive toward betterhealth for individuals and progress in medicine by developing superior pharmaceuticalproducts.
For company information, please visit Takeda Pharmaceuticals North America'sWeb site at www.tpna.com.

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