Eisai and Purdue Pharma Announce Key Phase 1 Clinical Studies of Lemborexant to be Presented at the 32nd Annual SLEEP Meeting

TOKYO, and STAMFORD, Conn., May 22, 2018 /PRNewswire/ --

Companies will present data on:

• Postural stability after middle-of-the-night awakening and next-morning compared to zolpidem ER
• Auditory awakening threshold
• Return to sleep latency compared to zolpidem ER (exploratory endpoint)
• Next-morning driving performance
• Safety evaluation

Eisai Co., Ltd. (CEO: Haruo Naito, "Eisai") and Purdue Pharma L.P. (President and CEO: Craig Landau, "Purdue Pharma") today announced that two key Phase 1 clinical studies (Study 108 and Study 106) of their investigational sleep/wake regulation agent lemborexant, including a comparison versus zolpidem tartrate extended release (zolpidem ER) and placebo on postural stability and other variables after middle-of-the-night awakening and the next-morning, will be presented at the 32^nd Annual Meeting of the Associated Professional Sleep Societies (SLEEP 2018), June 2-6, Baltimore, MD. Lemborexant is currently being studied for the treatment of multiple sleep disorders. Positive topline results from Studies 108 and 106, as well as the first-ever Phase 3 head-to-head superiority comparison versus zolpidem ER, were previously announced.

Of note, Eisai and Purdue Pharma will present data on a Phase 1 safety study (Study 108) that assessed the ability to awaken to an auditory stimulus in the middle of the night, as well as maintain postural stability – a predictor of risk for falls – and perform on tests of memory and attention in the middle of the night and the next morning. Additional data from this study, including tests of memory and attention performance are forthcoming and will be submitted for presentation at a future scientific forum. The study demonstrated that postural stability was significantly worse for zolpidem ER 6.25 mg compared with both lemborexant 5 mg and 10 mg in healthy volunteers age 55 and older. The study also measured how quickly participants could return to sleep after being awakened as an exploratory endpoint. Headache was the only adverse event (AE) observed in two or more people taking lemborexant.

Another Phase 1 study (Study 106), which evaluated residual next-morning effects via an on-road driving test, also achieved its primary objective, demonstrating no significant difference in next-morning driving performance versus placebo. This study was conducted versus placebo, with zopiclone included as a positive control, to evaluate potential next-morning impairment by measuring healthy adult and elderly participants' driving performance. In this study, the most common AEs observed in the lemborexant arms were somnolence, headache, and dry mouth.

"It is important that a treatment for sleep/wake regulation allows a patient to not only sleep well, but also wake well. Sleeping well includes the ability to fall asleep and stay asleep through the night, and waking well includes the ability to wake in the middle of the night, if needed, or the next day without impairment," said Russell Rosenberg, PhD, D.ABSM, a Principal Investigator in lemborexant studies and former Chairman of the Board of the National Sleep Foundation. "These studies provide important information about how lemborexant affects the ability to awaken after sleep."

"Our aspiration toward sleep/wake regulation is to improve the ability to fall and stay asleep, and address risks related to impairment due to residual effects from many current sleep agents," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. "These Phase 1 data provide important, clinically relevant information and strengthen our confidence in our investigational sleep/wake regulation agent, lemborexant, as we continue to work with Purdue Pharma to bring this investigational agent to patients living with sleep/wake disorders."

"Since 2015, Purdue Pharma and Eisai have been working collaboratively on the development of lemborexant, and we look forward to sharing our data with the scientific community at the premier world forum for clinical sleep medicine," said Marcelo Bigal, MD, PhD, Chief Medical Officer, Purdue Pharma.  

Lemborexant appears to impact an underlying reason for a patient's inability to sleep. Lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening excessive wakefulness without impeding the ability to awaken to external stimuli.

The following data will be presented by Eisai and Purdue Pharma at SLEEP 2018:

Discovered by Eisai, lemborexant – an investigational sleep/wake regulation agent – is being jointly developed by Eisai and Purdue Pharma. Information about ongoing clinical studies is available at clinicaltrials.gov. 

This release discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agent will successfully complete clinical development or gain health authority approval.

<Notes to editors>

1. About lemborexant 
   Lemborexant, an investigational dual orexin receptor antagonist, is Eisai's in-house discovered and developed small molecule compound that inhibits orexin neurotransmission by binding competitively to the two subtypes of orexin receptors (orexin receptor 1 and 2). In individuals with sleep/wake disorders, it is possible that the orexin system that regulates sleep and wakefulness is not functioning normally. During normal periods of sleep, the orexin system activity is suppressed, suggesting it is possible to purposefully counteract inappropriate wakefulness and facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission. Therefore, Eisai and Purdue have been developing and studying lemborexant as a potential treatment for multiple sleep disorders.
   
   A Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder (ISWRD) and mild to moderate Alzheimer's dementia is underway.
   
   
2. About Sleep Disorders 
   Population studies show that sleep disorders affect many more people worldwide than previously thought. Insomnia disorder is characterized by difficulty falling sleep, staying asleep or both, despite an adequate opportunity to sleep, that can lead to daytime consequences such as fatigue, difficulty concentrating and irritability. Insomnia disorder is the most common sleep disorder, with persistent insomnia symptoms experienced by approximately 10 percent of the adult population.
   
   Sleeping well is essential for good health, including brain health. Poor sleep is associated with a wide range of health consequences including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke and dementia, as well as adverse effects on mood and behavior.
   
   Experimental studies in animals and humans provide evidence of associations between sleep and inflammatory markers, and the association between sleep and mortality, as well as many diseases and disease risk factors; studies suggest an optimal sleep duration between seven and eight hours. Women are 1.4 times more likely than men to suffer from insomnia.
   
   Older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking and early waking, that can lead to less sleep time.
   
   
3. About Study 108
   Study 108 was a randomized, double-blind, four period, Phase 1 crossover study to evaluate the effect of lemborexant on postural stability, auditory awakening threshold, and cognitive performance in 56 healthy volunteers age 55 years and older. Participants were administered a single dose of placebo, lemborexant 5 mg, lemborexant 10 mg, or zolpidem ER 6.25 mg. The primary endpoint was change from time-matched baseline in postural stability for lemborexant compared to zolpidem ER at approximately four hours post dose.
   
   
4. About Study 106
   Study 106 was a randomized, double-blind, placebo- and active-controlled, four period, Phase 1 crossover study to evaluate the effect of lemborexant in 48 healthy adult and elderly volunteers to evaluate on-road driving performance. Participants were treated at bedtime with two out of three dose levels of lemborexant (2.5, 5 or 10 mg) and placebo for eight consecutive days, and zopiclone 7.5 mg as an active control on days one and eight only, with placebo given for the six days in between. The primary endpoint was to evaluate change of standard deviation of lateral position (SDLP) during an on-road driving test on the mornings following the first and last dose of drug in each treatment period.
   
   
5. About Eisai Inc.
   At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
   
   Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
   
   
6. About Purdue Pharma L.P.
   Purdue Pharma L.P. is a privately-held pharmaceutical company headquartered in Stamford, Conn. Purdue Pharma is part of a network of independent associated companies dedicated to providing patients and providers with innovative medicines. The company's leadership and employees are committed to serving healthcare professionals, patients and caregivers by providing quality products and educational resources that make a positive impact on healthcare – and on lives. For more information, please visit www.purduepharma.com.

SOURCE Eisai Co., Ltd.

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