On-Road Driving Safety Study of Investigational Lemborexant Published in SLEEP®

Lemborexant taken at bedtime had no significant effect on automobile driving performance the next morning in healthy adult and elderly volunteers

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Eisai Co., Ltd.

Jan 22, 2019, 08:01 ET

TOKYO and STAMFORD, Conn., Jan. 22, 2019 /PRNewswire/ -- Eisai Co., Ltd. (CEO: Haruo Naito, "Eisai") and Purdue Pharma L.P. (President and CEO: Craig Landau, MD, "Purdue Pharma") today announced the publication of a Phase 1 safety study evaluating the impact of bedtime administration with lemborexant on driving performance the following morning. The study, which met its primary endpoint, showed no statistically significant next-day impairment of driving performance in healthy adult and elderly volunteers compared to placebo. The study was recently published online by the peer-reviewed journal SLEEP^®, the official journal of the Sleep Research Society.

Lemborexant is an investigational agent being studied for the treatment of insomnia, a sleep-wake disorder. Lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli. Eisai and Purdue Pharma have conducted two Phase 3 safety and efficacy studies of lemborexant, which supported the New Drug Application submitted to the U.S. Food and Drug Administration (FDA) on December 27, 2018.

The study evaluated next-morning effects of lemborexant 2.5, 5, and 10 mg doses compared with placebo, on driving performance after single and repeated bedtime use in healthy adult and elderly volunteers, 21 years and older (n=48). Zopiclone 7.5 mg was selected as an active control to demonstrate assay sensitivity versus placebo. Driving performance was assessed by standard deviation of lateral position (SDLP), an index of road tracking error or "weaving," (measured in centimeters) during an on-road driving test conducted on the mornings following the first and last dose of study medication.

At all doses evaluated, lemborexant showed no clinically meaningful or statistically significant impairment of driving performance after either single (on the morning of Day 2) or multiple (on the morning of Day 9) dose administration compared to placebo. In contrast, zopiclone 7.5 mg significantly increased mean SDLP as compared to placebo. Additionally, no drives were stopped before completion because of drowsiness after use of lemborexant or placebo, whereas three out of 96 total drives (3.1 percent) after use of zopiclone were stopped early. All participants completed all treatments. Across all conditions, all adverse events (AEs) were of mild to moderate severity. The most commonly reported AEs for lemborexant across doses included somnolence, headache and dry mouth.

The Phase 1 study was designed to understand the impact of lemborexant on individuals' next-morning driving ability. The study protocol followed the FDA's guidance regarding inclusion of a positive control and placebo groups, elderly subjects, initial and steady state exposures for drugs with long half-lives, and crossover design.

"Our aspiration is to address unmet needs for patients suffering from insomnia so that they can fall asleep, stay asleep and wake without impairment," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. "Results from our Phase 1 safety study suggest no significant driving impairment with lemborexant, bolstering our confidence in this investigational agent being studied for the treatment of insomnia."

"The on-road driving test, which is performed in a limited number of locations worldwide, includes supervising study participants while they drive on open roads, instead of a driving simulator, providing important insights to a medication's impact on driving ability in real-world conditions," said John Renger, PhD, Vice President, Head of Research & Development and Regulatory Affairs, Purdue Pharma. "These data, along with outcomes from two robust Phase 3 studies, add to the growing body of scientific support for lemborexant and its potential utility in insomnia."

On Day 2 and Day 9, the difference in least squares (LS) mean SDLP was below 1.0 cm, compared to placebo, and not significant. The upper bound of the 95 percent confidence intervals (CIs) for the LS mean changes in SDLP were all below 2.4 cm for all three doses of lemborexant on Days 2 and 9, indicating there was not clinically meaningful driving impairment. The upper bound of the 95 percent CIs for the mean changes in SDLP for zopiclone was greater than 2.4 cm on Days 2 and 9, demonstrating assay sensitivity.

Lemborexant is being jointly developed by Eisai and Purdue Pharma for the treatment of multiple sleep-wake disorders, including insomnia disorder. Information about ongoing clinical studies is available at clinicaltrials.gov.

Eisai and Purdue Pharma are striving to address new unmet medical needs and to improve the lives of patients and their families.

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

1. About Lemborexant
Lemborexant is a novel investigational small molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness. In individuals with sleep-wake disorders, it is possible that orexin signaling which regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep.

Eisai and Purdue Pharma are investigating lemborexant as a potential treatment option for multiple sleep-wake disorders, such as insomnia. Additionally, a Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate Alzheimer's dementia is underway.

2. About Study 106
A randomized, double-blind, placebo- and active-controlled, four-period, Phase 1 incomplete crossover study evaluated the effect of lemborexant on on-road driving performance in 48 healthy adult and elderly volunteers, 23 to 78 years of age (mean age 58.5 years). Participants (n=24 age 65 and older and n=24 age 23 to 64) were treated at bedtime with two out of three dose levels of lemborexant (2.5, 5 or 10 mg) and placebo for eight consecutive nights, and zopiclone 7.5 mg as an active control on the first and last night only, with placebo given on intervening nights. Standardized one-hour on-road driving tests on the morning of Day 2 and Day 9 were started approximately nine hours post-dose.

In the on-road test, participants drove a specially instrumented vehicle for about one hour over a 100 km (approximately 60 miles) primary highway circuit, accompanied by a licensed driving instructor. The task was to drive with a steady lateral position between the delineated boundaries of the slower traffic lane, while maintaining a constant speed of 95 km/h. A camera on top of the car continuously registered the lateral position of the car on the road with respect to the left lane delineation.

3. About Sleep Disorders
Population studies show that sleep disorders affect many more people worldwide than previously thought. Insomnia disorder is the most common sleep disorder affecting approximately 30 percent of the adult population worldwide. Insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep, which can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.

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 disease risk factors, diseases and mortality. 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.

4. About Eisai Co., Ltd
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Neurology and Oncology.

Furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit www.eisai.com.

5. About Purdue Pharma L.P.
Purdue Pharma L.P. develops and provides prescription medicines that meet the evolving needs of healthcare professionals, patients, and caregivers. We were founded by physicians and we are currently led by a physician. Beyond our efforts to provide quality medications, Purdue Pharma is committed to supporting national, regional and local collaborations to drive innovations in patient care. Privately held, Purdue Pharma is pursuing a pipeline of new medications and technologies through internal research & development and strategic industry partnerships. For more information, please visit www.purduepharma.com.