Eisai Announces U.S. Availability of DAYVIGO™ (lemborexant) CIV, a New Treatment Option for Adults With Insomnia

WOODCLIFF LAKE, N.J., June 1, 2020 /PRNewswire/ -- Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd., today announced the availability of DAYVIGO™ (lemborexant) CIV for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.1 In clinical studies, DAYVIGO helped some people with insomnia fall asleep faster and stay asleep longer compared to placebo. The effects of DAYVIGO at first use were generally consistent with later timepoints.

"Given up to 30% of adults worldwide report insomnia symptoms and the increase in sleep problems due to the life changes caused by the COVID-19 pandemic environment, it is crucial to offer patients treatment options that may help them fall asleep and stay asleep," said Russell Rosenberg, PhD, D.ABSM, a principal investigator in the DAYVIGO clinical studies and former Chairman of the Board of the National Sleep Foundation. "DAYVIGO may be an appropriate treatment option for some of these patients."

The U.S. Food and Drug Administration's (FDA) approval of DAYVIGO was based on findings from the robust lemborexant clinical development program. This included two pivotal Phase 3 studies (SUNRISE 2 and SUNRISE 1), which evaluated DAYVIGO versus placebo and active comparator for up to one month and DAYVIGO versus placebo for six-months, respectively, in a total of about 2,000 adult patients with insomnia.

The most common adverse reaction (reported in 5% or more of patients treated with DAYVIGO and at least twice the rate of placebo) was somnolence (DAYVIGO 10 mg, 10%; DAYVIGO 5 mg, 7%; placebo, 1%). Analyses 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 contains lemborexant, a Schedule IV controlled substance. 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.

DAYVIGO at 5 mg and 10 mg doses did not cause significant impairment in next-morning driving performance in healthy adult or elderly subjects (compared with placebo).1 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.1

"Insomnia is often a chronic condition for which patients may require treatment over an extended period of time, so the long-term safety of medications is an important consideration for patients and health care professionals," said Lynn Kramer, MD, Chief Clinical Officer, Neurology Business Group, Eisai. "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. We are pleased to make DAYVIGO available to patients in the U.S."

The recommended dosage of DAYVIGO is one 5 mg tablet taken no more than once per night, immediately before going to bed, with at least seven hours remaining before the planned time of awakening.1 The dose may be increased to the maximum recommended dose of 10 mg based on clinical response and tolerability. Time to sleep onset may be delayed if taken with or soon after a meal.1

"The U.S. is the first country in which DAYVIGO is available, and we are excited by its potential to help patients sleep better," said Ivan Cheung, Chairman, Eisai Inc., and Global President, Neurology Business Group, Eisai Co., Ltd. "DAYVIGO is an important addition to Eisai's rapidly growing neurology portfolio, which underscores our leadership in neuroscience. Eisai remains committed to discovering and developing innovative solutions to unmet medical needs that benefit patients and their families."

Lemborexant is presumed to inhibit orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). Orexin signaling is believed to promote periods of wakefulness.2 In individuals with insomnia, it is possible that orexin signaling that regulates wakefulness is not functioning normally.

Diagnostic criteria 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 night per week and is present for at least three months.3 Patients with insomnia symptoms should speak to a health care professional about treatment options. Health care professionals and patients in the U.S. can visit DAYVIGO.com for more information and a savings card offer (restrictions apply).

<Notes to editors>

1. About Lemborexant
Lemborexant is a 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.2 In individuals with insomnia, it is possible that orexin signaling regulating wakefulness is not functioning normally.

INDICATION
DAYVIGO (lemborexant) is an orexin receptor antagonist indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • DAYVIGO is contraindicated in patients with narcolepsy.

WARNINGS AND PRECAUTIONS

  • Central Nervous System (CNS) Depressant Effects and Daytime Impairment:
    DAYVIGO can impair daytime wakefulness. CNS depressant effects may persist in some patients up to several days after discontinuing DAYVIGO. Prescribers should advise patients about the potential for next-day somnolence.
       
    Driving ability was impaired in some subjects taking DAYVIGO 10 mg. Risk of daytime impairment is increased if DAYVIGO is taken with less than a full night of sleep remaining or at a higher than recommended dose. If taken in these circumstances, patients should not drive or engage in activities requiring mental alertness.
        
    Use with other classes of CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment. Dosage adjustments of DAYVIGO and concomitant CNS depressants may be necessary when administered together. Use of DAYVIGO with other insomnia drugs is not recommended. Patients should be advised not to consume alcohol in combination with DAYVIGO.
        
    Because DAYVIGO can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls.
        
  • Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-Like Symptoms:
    Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions can occur with DAYVIGO. Prescribers should explain these events to patients.
       
    Symptoms similar to mild cataplexy can occur with DAYVIGO and can include periods of leg weakness lasting from seconds to a few minutes, can occur either at night or during the day, and may not be associated with identified triggering event (e.g., laughter or surprise).
         
  • Complex Sleep Behaviors:
    Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as DAYVIGO. Events can occur in hypnotic-naïve and hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of DAYVIGO, with or without the concomitant use of alcohol and other CNS depressants. Discontinue DAYVIGO immediately if a patient experiences a complex sleep behavior.
        
  • Patients with Compromised Respiratory Function:
    The effect of DAYVIGO on respiratory function should be considered for patients with compromised respiratory function. DAYVIGO has not been studied in patients with moderate to severe obstructive sleep apnea (OSA) or chronic obstructive pulmonary disease (COPD).
       
  • Worsening of Depression/Suicidal Ideation:
    Incidence of suicidal ideation or suicidal behavior, as assessed by questionnaire, was higher in patients receiving DAYVIGO than placebo (0.3% for DAYVIGO 10 mg, 0.4% for DAYVIGO 5 mg, and 0.2% for placebo).
      
    In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed at any one time.
         
    The emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
        
  • Need to Evaluate for Comorbid Diagnoses:
    Treatment of insomnia should be initiated only after careful evaluation of the patient. Reevaluate for comorbid conditions if insomnia persists or worsens after 7 to 10 days of treatment. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or medical disorder and can emerge during the course of treatment with sleep-promoting drugs such as DAYVIGO.

ADVERSE REACTIONS

  • The most common adverse reaction (reported in 5% of patients treated with DAYVIGO and at least twice the rate of placebo) with DAYVIGO was somnolence (10% for DAYVIGO 10 mg, 7% for DAYVIGO 5 mg, 1% for placebo).

DRUG INTERACTIONS

  • CYP3A Inhibitors: The maximum recommended dose of DAYVIGO is 5 mg no more than once per night when co-administered with weak CYP3A inhibitors. Avoid concomitant use of DAYVIGO with strong or moderate CYP3A inhibitors.
        
  • CYP3A Inducers: Avoid concomitant use of DAYVIGO with moderate or strong CYP3A inducers.

USE IN SPECIFIC POPULATIONS

  • Pregnancy and Lactation: There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to DAYVIGO during pregnancy. Healthcare providers are encouraged to register patients in the DAYVIGO pregnancy registry by calling 1-888-274-2378. There are no available data on DAYVIGO use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
       
    There are no data on the presence of lemborexant in human milk, the effects on the breastfed infant, or the effects on milk production. Infants exposed to DAYVIGO through breastmilk should be monitored for excess sedation.
  • Geriatric Use: Exercise caution when using doses higher than 5 mg in patients ≥65 years old.
      
  • Renal Impairment: Patients with severe renal impairment may experience an increased risk of somnolence.
        
  • Hepatic Impairment: The maximum recommended dose of DAYVIGO is 5 mg in patients with moderate hepatic impairment. DAYVIGO is not recommended in patients with severe hepatic impairment. Patients with mild hepatic impairment may experience an increased risk of somnolence.

DRUG ABUSE AND DEPENDENCE

  • DAYVIGO is a Schedule IV-controlled substance.
  • Because individuals with a history of abuse or addiction to alcohol or other drugs may be at increased risk for abuse and addiction to DAYVIGO, follow such patients carefully.

For more information about DAYVIGO, see full Prescribing Information.

2. About Insomnia
Population studies show that sleep disorders affect many more people worldwide than previously thought.4 Insomnia symptoms affect approximately 30% of the adult population worldwide.5 Insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep.6

Diagnostic criteria 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 night per week and is present for at least three months.3

Sleeping well is essential for good health. Studies suggest an optimal sleep duration between seven and eight hours.7

Women are 1.4 times more likely than men to suffer from insomnia.8 Older adults also have a 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.9

3. About SUNRISE 2 (Study 1)1
SUNRISE 2: 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.

4. About SUNRISE 1 (Study 2)1
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 sleep efficiency (SEF) and wake after sleep onset (WASO). These endpoints were measured by overnight polysomnography monitoring.

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). 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 and follow us on Twitter and LinkedIn.

References
1 Eisai Inc. DAYVIGO Full Prescribing Information. 2020.
2 Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011;51:243‐266.
3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA: American Psychiatric Publishing, 2013.
4 Ferrie JE, et al. Sleep epidemiology – a rapidly growing field. Int J Epidemiol. 2011;40(6):1431–1437.
5 Roth T. Insomnia: definition, prevalence, etiology and consequences. J Clin Sleep Med. 2007;3(5 Suppl):S7–S10.
6 Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health problem. Washington, DC: National Academies Press. 2006.
7 Cappuccio FP, et al. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep. 2010;33(5):585-592.
8 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. Biol Psychiatry. 2011;69:592– 600.
9 Crowley K. Sleep and sleep disorders in older adults. Neuropsychol Rev. 2011;21(1):41-53.

Contact:

Eisai Inc.
Libby Holman
201-753-1945
libby_holman@eisai.com

 

SOURCE Eisai Inc.

Type Press Release

Date Released June 01, 2020

We are pleased to make DAYVIGO available to patients in the U.S. - Lynn Kramer, MD, Chief Clinical Officer, Neurology Business Group, Eisai
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