Pivotal Phase 3 Study of DAYVIGO(TM) (lemborexant) for the Treatment of Insomnia Disorder Published in JAMA Network Open

WOODCLIFF LAKE, N.J., Dec. 27, 2019 /PRNewswire/ -- Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd., today announced that JAMA Network Open (www.jamanetwork.com) published results of SUNRISE 1 (Study 304), a pivotal Phase 3 head-to-head study that compared DAYVIGO™ (lemborexant) to placebo and an active comparator in patients with insomnia disorder.¹ In this study, DAYVIGO therapy significantly improved both sleep onset and sleep maintenance compared with placebo.

"We are pleased to share these important study results in JAMA Network Open," said Lynn Kramer, MD, Chief Clinical Officer, Neurology Business Group, Eisai. "The study featured in this publication provides insights into why this agent may make an important difference for patients living with insomnia."

SUNRISE 1 was a global, randomized, double-blind, placebo-controlled, active comparator parallel-group study of 1,006 adults 55 years of age or older with insomnia disorder receiving DAYVIGO 5 mg or 10 mg, an active comparator or placebo for one month at bedtime. The primary study endpoint was the change from baseline in latency to persistent sleep for DAYVIGO therapy versus placebo. Key secondary endpoints were changes from baseline in sleep efficiency and wake after sleep onset compared with placebo, and wake after sleep onset in the second half of the night compared with the active comparator. Treatment-emergent adverse events reported in ≥2% of participants in any active treatment group included headache (6.2% for placebo, 5.3% for active comparator, 6.4% for DAYVIGO 5 mg, and 4.9% for DAYVIGO 10 mg) and somnolence (1.9% for placebo, 1.5% for active comparator, 4.1% for DAYVIGO 5 mg, and 7.1% for DAYVIGO 10 mg). Full study results can be accessed in the JAMA Network Open publication.

DAYVIGO was approved by the U.S. Food and Drug Administration on December 20, 2019 for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.² The FDA has recommended that DAYVIGO be classified as a controlled substance and this recommendation has been submitted to the U.S. Drug Enforcement Administration (DEA). DAYVIGO will be commercially available following scheduling by the DEA, which is expected to occur within 90 days of the product's approval. The Full Prescribing Information is available here.

JAMA Network Open is an international, peer-reviewed, open access, general medical journal, and is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.

<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. In individuals with sleep-wake disorders, it is possible that orexin signaling that regulates 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 increases the risk of CNS depression. 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, hypnagogic/hypnopompic hallucinations, and symptoms similar to mild cataplexy can occur with the use of DAYVIGO. Prescribers should explain these events to patients.
   
• Complex Sleep Behaviors:
  Complex sleep behaviors 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 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 Co-Morbid Diagnoses:
  Treatment of insomnia should be initiated only after careful evaluation of the patient. Re-evaluate for comorbid conditions if insomnia persists or worsens after 7 to 10 days of treatment.

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

• Controlled substance scheduling of DAYVIGO is pending review by the U.S. Drug Enforcement Administration (DEA).
• 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 Sleep Disorders 
Population studies show that sleep disorders affect many more people worldwide than previously thought.³ Insomnia symptoms affect approximately 30% of the adult population worldwide.⁴ 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.^5,6

Sleeping well is essential for good health, including brain health. Poor sleep is associated with a wide range of health consequences.⁵

Experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases, and mortality.⁷ Studies suggest an optimal sleep duration between seven and eight hours.⁸

Women are 1.4 times more likely than men to suffer from insomnia.⁹ 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.¹⁰

3.     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 Rosenberg R, et al. Comparison of lemborexant with placebo and zolpidem extended release in older adults with insomnia disorder: A phase 3 randomized clinical trial. JAMA Netw Open. 2019
² Eisai Inc. DAYVIGO Full Prescribing Information. 2019.
³ Ferrie JE, et al. Sleep epidemiology – a rapidly growing field. Int J Epidemiol. 2011;40(6):1431–1437.
⁴ Roth T. Insomnia: definition, prevalence, etiology and consequences. J Clin Sleep Med. 2007;3(5 Suppl):S7–S10. 
⁵ Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health problem. Washington, DC: National Academies Press. 2006.
⁶ Ohayon MM, et al. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97-111.
⁷ Cappuccio FP, et al. Sleep and cardio-metabolic disease. Curr Cardiol Rep. 2017;19:110.
⁸ 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.
⁹ 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.
¹⁰ Crowley K. Sleep and sleep disorders in older adults. Neuropsychol Rev. 2011;21(1):41-53.

Contact:

Eisai Inc.
James Merse
551-502-2710 
James_Merse@eisai.com  

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