9/28/2020
`
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`
`Me
`
` Home ＞ News Release ＞ 2020 Release ＞
`
`
`
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT
`OPTION FOR ADULTS WITH INSOMNIA
`
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™
`(LEMBOREXANT) CIV IN THE UNITED STATES AS A
`TREATMENT OPTION FOR ADULTS WITH INSOMNIA
`
`For Print
`
`（527KB）
`
`June 2, 2020
`
`Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its U.S. subsidiary
`Eisai Inc. has launched its in-house discovered orexin receptor antagonist DAYVIGO™ (lemborexant) CIV for
`
`the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep
`maintenance in the U.S. on June 1, 2020.
`
`Discovered at Eisaiʼs Tsukuba Research Laboratories and developed in-house, DAYVIGO is a small-molecule
`compound. The mechanism of action in the treatment of insomnia is presumed to be through antagonism of
`orexin receptors . The orexin neuropeptide signaling system plays a role in wakefulness . Blocking the
`1
`1
`binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is
`thought to suppress wake drive. Lemborexant binds to orexin receptors OX1R and OX2R and acts as a
`competitive antagonist (IC50 values of 6.1 nM and 2.6 nM, respectively).
`
`DAYVIGO was approved in the U.S. by the U.S. Food and Drug Administration (FDA) based on findings from
`the lemborexant clinical development program, which included two pivotal Phase 3 studies (SUNRISE 1 and
`2
`SUNRISE 2) in nearly 2,000 adult patients with insomnia.
`
`SUNRISE 1 was a one month, randomized, double-blind, placebo- and active-controlled multi-center,
`parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older
`who met DSM-5 (the Diagnostic and Statistical Manual of Mental Disorders ‒ 5th edition) criteria for
`insomnia disorder. The primary efficacy endpoint was the mean change in latency to persistent sleep (LPS;
`defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness)
`from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (PSG)
`monitoring. The secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of
`treatment (day 29/30) in sleep efficiency (SEF) and wake after sleep onset (WASO) measured by PSG. In
`SUNRISE 1, DAYVIGO 5 mg and 10 mg demonstrated statistically significant superiority on the primary
`efficacy measure, LPS, compared to placebo. DAYVIGO 5 mg and 10 mg demonstrated statistically
`significant improvement in SE and WASO compared to placebo and active-controlled.
`
`SUNRISE 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in
`adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. The primary efficacy endpoint
`was the mean change from baseline to end of treatment at six months for patient-reported (subjective)
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`1/6
`
`Page 1 of 6
`
`EISAI EXHIBIT 1022
`
`

`

`9/28/2020
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`sleep onset latency (sSOL), defined as the estimated minutes from the time that the subject attempted to
`sleep until sleep onset. Pre-specified secondary efficacy endpoints for sleep maintenance were change from
`baseline to end of treatment at six months for patient reported sleep efficiency (sSEF; defined as the
`proportion of time spent asleep per time in bed) and wake after sleep onset (sWASO; defined as the minutes
`of wake from the onset of sleep until wake time). The pre-specified primary and secondary efficacy
`endpoints were measured using a Sleep Diary. In SUNRISE 2, DAYVIGO 5 mg and 10 mg demonstrated
`statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. DAYVIGO 5
`mg and 10 mg also showed statistically significant superiority in sSEF and sWASO.
`1
`
`Analyses in both studies suggested DAYVIGO was not associated with rebound insomnia, and there was no
`evidence of withdrawal effects following treatment discontinuation, suggesting it does not produce physical
`dependence in those taking it for up to one year. DAYVIGO is the first FDA-approved insomnia medication
`with safety data over a 12-month treatment period and with sleep onset and sleep maintenance efficacy
`data over a six-month treatment period in a pivotal clinical study.
`
`The most common adverse reaction (reported in 5% or more of patients treated with DAYVIGO and at least
`twice the rate of placebo) in the SUNRISE1 and SUNRISE2 (SUNRISE2 was initiated 30 days after first
`dosing) studies was somnolence (DAYVIGO 10 mg, 10%; DAYVIGO 5 mg, 7%; placebo, 1%).
`
`In a special safety study (Study 106) , DAYVIGO at 5 mg and 10 mg doses did not cause statistically
`3
`significant impairment in next morning driving performance in healthy adult or elderly subjects (compared
`with placebo). Impairment was seen in some people taking the 10 mg dose. Patients using the 10 mg dose
`should be cautioned about the potential for next-morning driving impairment because there is individual
`variation in sensitivity to DAYVIGO. Additional special safety studies (Study 108) evaluated middle-of-the-
`4
`night safety, next morning postural stability and memory. The effects of Dayvigo on next day postural
`stability and memory were evaluated in two randomized, placebo and active-controlled trials in healthy
`subjects and insomnia patients age 55 and older. There were no meaningful differences between DAYVIGO
`and placebo on next-day postural stability or memory at either dose. Patients should be cautioned about the
`potential for middle-of-the-night postural instability as well as attention and memory impairment.
`
`DAYVIGO (5 mg, 10 mg tablets) received approval from the U.S. FDA in December 2019, and was designated
`as a Schedule IV controlled substance by the U.S. Drug Enforcement Administration (DEA) in April 2020.
`According to this Schedule IV designation, individuals with a history of abuse or addiction to alcohol or other
`drugs may be at an increased risk for abuse and addiction to DAYVIGO and such patients should be followed
`carefully. Eisai received manufacturing and marketing approval for DAYVIGO as an insomnia treatment in
`Japan in January 2020, and was included in Japanʼs National Health Insurance Drug Price List in April 2020.
`It is being prepared for launch in Japan. Eisai has also submitted a new drug application seeking approval of
`this agent for use in the treatment of insomnia in Canada in August 2019.
`
`Insomnia is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate
`opportunity to sleep
`. Insomnia is one of the most common sleep-wake disorders with high prevalence.
`5, 6
`Approximately 30% of adults worldwide have symptoms of insomnia
`, and many of them persist for months
`7, 8
`to years.
`
`
`With the launch of DAYVIGO and through its continuing research and development efforts focusing on orexin
`biology, Eisai aspires to improve the lives of patients suffering from sleep disorders.
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`2/6
`
`Page 2 of 6
`
`

`

`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`
`9/28/2020
`
`
`
`Media Inquiries:
`Public Relations Department,
`Eisai Co., Ltd.
`+81-(0)3-3817-5120
`
`
`[Notes to editors]
`1. About DAYVIGO (lemborexant)
`TM
`Lemborexant is Eisaiʼs in-house discovered and developed small molecule that binds to orexin receptors,
`OX1R and OX2R (IC50 values of 6.1 nM and 2.6 nM, respectively) and acts as a competitive antagonist with
`stronger inhibition effect to OX2R. In individuals with insomnia, it is possible that orexin signaling regulating
`wakefulness is not functioning normally.
`The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-
`2
`promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake
`drive. DAYVIGO is being prepared for launch in Japan. Eisai has also submitted a new drug application
`seeking approval of this agent for use in the treatment of insomnia in Canada in August 2019.
`
`For further information on DAYVIGO in the United States, including Important Safety Information (ISI),
`please visit the DAYVIGO website (DAYVIGO.com ).
`
`2. About Sleep-Wake Disorders and Insomnia
`Sleep-wake disorders consist of disease categories such as insomnia, Irregular Sleep-Wake Rhythm
`Disorder (ISWRD), hypersomnia and breathing-related sleep disorders. Among the sleep-wake disorders,
`insomnia is the most common with persistent insomnia symptoms experienced by approximately 30 percent
`of the adult population worldwide.
` Insomnia disorder is characterized by difficulty falling asleep, staying
`7,8
`asleep, or both, despite an adequate opportunity to sleep.
`5,6
`Diagnostic criteria in the U.S. for insomnia disorder include if the sleep disturbance causes clinically
`significant distress or impairment in social, occupational, educational, academic, behavioral or other
`important areas of functioning, occurs at least three nights per week and is present for at least three
`months.
`Sleeping well is essential for good health , and studies suggest an optimal sleep duration between seven
`9
`and eight hours.
` Poor sleep is associated with a wide range of health consequences.
`10
`5,12
`Women are 1.4 times more likely than men to suffer from insomnia.
` Older adults also have higher
`11
`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.
`12
`
`3. About SUNRISE 1 (Study 304)
`2
`SUNRISE 1 is a one-month trial in adult female patients age 55 and older and male patients 65 years and
`older who met DSM-5 criteria for insomnia disorder. Patients were randomized to placebo (n=208),
`DAYVIGO 5 mg (n=266) or 10 mg (n=269), or active comparator (n=263) once nightly. The primary efficacy
`endpoint was the mean change from baseline to end of treatment at Days 29/30 in latency to persistent
`sleep (LPS; the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness).
`Secondary efficacy endpoints were the mean change from baseline to end of treatment at Days 29/30 in
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`3/6
`
`Page 3 of 6
`
`

`

`9/28/2020
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`sleep efficiency (SEF) and wake after sleep onset (WASO). These endpoints were measured by overnight
`polysomnography monitoring.
`
`4. About SUNRISE 2 (Study 303)
`2
`SUNRISE 2 is a six-month placebo-controlled treatment trial with a 6-month parallel-group extension period
`including adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. Patients were
`randomized to placebo (n=325), DAYVIGO 5 mg (n=323), or DAYVIGO 10 mg (n=323) once nightly. The
`primary efficacy endpoint was the mean change from baseline to end of treatment at six months for
`subjective sleep onset latency (sSOL; the estimated minutes from the time that the patient attempted to
`sleep until sleep onset). Secondary efficacy endpoints were mean change from baseline to end of treatment
`at six months subjective sleep efficiency (sSEF; the proportion of time spent asleep per time in bed) and
`wake after sleep onset (sWASO; the minutes of wake from the onset of sleep until wake time). These
`endpoints were measured by sleep diary.
`
`5. About Study 106
`3
`Study 106 was a randomized, double-blind, placebo- and active-controlled, four period, crossover Phase I
`study to evaluate the effect of lemborexant in 48 healthy adults and elderly volunteers (23 to 58 years of
`age, mean: 58.5 years old) to evaluate on-road driving performance. Volunteers (65 years and older: 24, 23 to
`64 years old: 24) 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. Zopiclone 7.5 mg as an active control was administered 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 conducted after the first (in
`the morning of Day 2) and last day (in the morning of Day 9) of treatment administration after 9-hour dose.
`In the on-road test, the volunteers drove a specially instrumented vehicle for about one hour over 100km
`(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 95km/h.
`Although lemborexant at doses of 5 mg and 10 mg did not cause statistically significant impairment in next-
`morning driving performance in adult or elderly subjects (compared with placebo), driving ability was
`impaired in some subjects taking 10 mg lemborexant.
`
`6. About Study 108
`4
`Study 108 was a randomized, double-blind, four period crossover Phase I study to evaluate the effect of
`lemborexant on postural stability, auditory awakening threshold, and cognitive performance in 56 healthy
`volunteers 55 years and older. Participants were treated at bedtime with a single dose of placebo,
`lemborexant 5 mg, lemborexant 10 mg, or active control. There was a statistically significant increase in
`body sway for both doses of lemborexant compared with placebo. The next morning, shortly after the end of
`eight hours in bed neither dose of lemborexant had statistically significant residual effects on this measure
`of postural stability as compared to placebo.
`
`
`References
`Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities.
`. 2011;51:243‐266.
`Eisai Inc. DAYVIGO Full Prescribing Information. 2020.
`
`1 2 3
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`4/6
`
`Page 4 of 6
`
`Annu Rev
`Pharmacol Toxicol
`

`

`9/28/2020
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`Vermeeren A, et al. On-the-road driving performance the morning after bedtime administration of
`lemborexant in healthy adult and elderly volunteers.
` 2019 42 (4): zsy260.
`Murphy P, et al. Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening
`threshold, postural stability, and cognitive performance in healthy older participants in the middle of the
`night and upon morning awakening,
` 2020: 16(5):765-773.
`Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health problem.
`Washington, DC: National Academies Press. 2006.
`Ohayon MM, et al. Epidemiology of insomnia: what we know and what we still need to learn.
` 2002;6(2):97-111.
`Ferrie JE, et al. Sleep epidemiology ‒ a rapidly growing field
`Roth T. Insomnia: definition, prevalence, etiology and consequences.
`Suppl):S7‒S10.
`Sleep duration and all-cause mortality: a systematic review and meta-analysis of
`Cappuccio FP, et al.
`2010;33(5):585-592.
`prospective studies.
`Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the
`community.
`2017;89(12):1244-1250.
`Roth T, et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR;
`International Statistical Classification of Diseases and Related Health Problems, tenth revision; and
`Research Diagnostic Criteria/International Classification of Sleep Disorders, second edition criteria:
`results from the America Insomnia Survey
` 2011;69:592‒ 600.
`Crowley K. Sleep and sleep disorders in older adults.
`. 2011;21(1):41-53.
`
`11
`
`12
`
`Full text
`
`（527KB）
`
`Search
`
`News Release
`
`News release search
`
`Search
`
`2020 Release
`
`2019 Release
`
`2018 Release
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`5/6
`
` 2011;40(6):1431‒1437.
`. 2007;3(5
`
`4
`
`5 6 7 8 9 1
`
`0
`
`Page 5 of 6
`
`Sleep.
` J. Clinical Sleep Medicine.
`Sleep Med
`Rev.
`. Int J Epidemiol.
`J Clin Sleep Med
`
` Sleep.
` Neurology.
`. Biol Psychiatry.
`Neuropsychol Rev
`

`

`9/28/2020
`
`EISAI LAUNCHES NEW INSOMNIA DRUG DAYVIGO™ (LEMBOREXANT) CIV IN THE UNITED STATES AS A TREATMENT OPTION …
`
`2017 Release
`
`2016 Release
`
`2015 Release
`
`2014 Release
`
`2013 Release
`
`2012 Release
`
`2011 Release
`
`2010 Release
`
`2009 Release
`
`2008 Release
`
`2007 Release
`
`Privacy Policy
`
`SNS Community Guidelines
`
`Sitemap
`
`Terms of Use
`
`Accessibility
`
`Twitter Eisai official account
`
`Copyright © Eisai Co., Ltd. All Rights Reserved.
`
`https://www.eisai.com/news/2020/news202025.html#:~:text=DAYVIGO (5 mg%2C 10 mg,(DEA) in April 2020
`
`6/6
`
`Page 6 of 6
`
`