Europe’s first dual orexin receptor antagonist – QUVIVIQ (daridorexant) –
granted approval to improve both nighttime symptoms and daytime functioning in
adults with chronic insomnia disorder QUVIVIQ™▼ is indicated for the treatment
of adult patients with insomnia characterized by symptoms present for at least
three months and considerable impact on daytime functioning Comprehensive
nighttime efficacy and unique daytime functioning data, together with a
favorable safety profile, are included in the QUVIVIQ product label This
approval makes QUVIVIQ, Europe's first dual orexin receptor antagonist, a new
targeted mechanism of action that decreases overactive wakefulness in insomnia
Allschwil, Switzerland – May 3, 2022
Idorsia Ltd (SIX: IDIA) today announced the European Commission (EC) has
granted marketing authorization for QUVIVIQ™▼ (daridorexant) for the treatment
of adult patients with insomnia characterized by symptoms present for at least
three months and considerable impact on daytime functioning. 1 Chronic insomnia
disorder is one of the most prevalent sleep disorders in Europe, affecting
between 6%-12% of the adult population, 2 and impacting both physical and
mental health. 3 , 4
With this approval, QUVIVIQ becomes the first dual orexin receptor antagonist
(DORA) in the European Union (EU) for the treatment of insomnia. Rather than
inducing sleep through broad inhibition of brain activity, QUVIVIQ blocks only
the activation of orexin receptors. 1 Consequently, QUVIVIQ decreases the wake
drive, allowing sleep to occur, without altering the proportion of sleep
The recommended dose of QUVIVIQ is one tablet of 50 mg once per night, taken
orally in the evening within 30 minutes before going to bed. 1 In certain
circumstances, such as patients with moderate hepatic impairment or who are
taking moderate CYP3A4 inhibitors, the recommended dose is 25 mg once per
Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia , commented:
“As our first treatment authorized in the EU, the approval of QUVIVIQ marks a
significant medical advancement in the management of insomnia and a big
milestone for Idorsia. I am delighted to see the comprehensive long-term safety
and efficacy data we have generated with QUVIVIQ included in an outstanding
label. In particular, I’m pleased with the description of the unique daytime
functioning improvement data, which I believe will revolutionize the way
insomnia is treated in the EU. We are incredibly proud to bring the therapeutic
benefits of QUVIVIQ, the first dual orexin receptor antagonist in Europe, to
clinicians and patients. We expect to make it available in the first countries
before the end of the year.”
The EC decision is supported by robust Phase 3 results – recently published in
The Lancet Neurology – which demonstrated that at the recommended dose, QUVIVIQ
improved sleep onset, sleep maintenance and self-reported total sleep time in
adults with chronic insomnia disorder. 5 A major focus of the trials was to
evaluate the impact of QUVIVIQ on daytime functioning in patients with insomnia
disorder, as assessed by IDSIQ, a patient-reported outcomes instrument
specifically developed and validated according to FDA guidelines, to measure
daytime functioning in patients with insomnia. The recommended dose of QUVIVIQ
demonstrated highly statistically significant improvement in the daytime
sleepiness domain of IDSIQ, which means patients reported feeling less mentally
and physically tired, less sleepy and more energetic during the day, at months
one and three compared to placebo, with a favorable safety profile. 1 ,5 In
clinical trials, the most frequently reported adverse reactions were headache
and somnolence. 1 The majority of adverse reactions were mild to moderate in
intensity. 1 No evidence of a dose-relationship for the frequency or severity
of adverse reactions was observed. 1 The adverse reaction profile in elderly
patients was consistent with younger patients. 1 Somnolence was reported in 3%
and 2% of patients treated with QUVIVIQ 25 mg and 50 mg, respectively, compared
to 2% of subjects on placebo. 1 The marketing authorization was also supported
by a long-term follow-up extension study, which together with the pivotal
trials, provides clinical data for up to 12 months of continuous treatment. 1
For more information on the marketing authorization of QUVIVIQ in the European
Union, please review the Summary of Product Characteristics (SmPC) .
Professor Damien Léger, Université Paris Cité , France, commented:
“Sleep is an essential pillar for good physical and mental health to ensure
optimal functioning throughout the day. Chronic insomnia disorder is persistent
in many patients and has direct consequences, such as impaired daytime
function, decreased workplace productivity, injuries and accidents, making
insomnia not only a disease of the night, but one that also markedly affects
the day and a patient’s well-being. QUVIVIQ, which can be used long-term,
effectively improves sleep parameters and people’s ability to function better
during the day, while avoiding major safety concerns, fulfilling the major
medical requirements for insomnia management. This is great news for
the millions of adults and elderly people across the EU living with chronic
About QUVIVIQ (daridorexant) in insomnia disorder
Studies over the past decades have shown that hyperarousal processes in the
brain play a key role in the pathology of insomnia. 6 Chronic insomnia disorder
is the result of continued brain hyperarousal that requires sustained
management with therapy suitable for daily use over months. 7 Orexin is a
neuropeptide, a small protein-like molecule, produced by the brain that
promotes wakefulness. 1 , 6 QUVIVIQ reduces nocturnal hyperarousal to improve
sleep (onset and maintenance) without next-morning residual effects in insomnia
patients, and thus improve daytime functioning. 5
Regulatory status of daridorexant
Marketing authorization of QUVIVIQ in Europe follows a positive opinion issued
on 24 February by the European Medicines Agency’s (EMA) Committee for Medicinal
Products for Human Use (CHMP). The approval is valid in all European Union
Member States, as well as the European Economic Area countries Iceland,
Liechtenstein and Norway, and Northern Ireland under the Northern Ireland
Protocol. In Great Britain, a separate application for the use of daridorexant
for the same indication has been submitted to the Medicines and Healthcare
products Regulatory Agency (MHRA) via the European Commission Decision Reliance
Daridorexant is currently under review with Swissmedic and Health Canada. In
January 2022, QUVIVIQ (daridorexant) was approved by the US Food and Drug
Administration (FDA) for the treatment of adult patients with insomnia,
characterized by difficulties with sleep onset and/or sleep maintenance. 8
Notes to the editor
About insomnia disorder
Insomnia disorder is defined as difficulty initiating or maintaining sleep,
causing clinically significant distress or impairment in important areas of
daytime functioning. 3 This impact on sleep quantity or quality should be
present for at least three nights per week, lasts for at least three months,
and occurs despite an adequate opportunity to sleep. 3
Insomnia is a condition of overactive wake signaling and studies have shown
that areas of the brain associated with wakefulness remain more active during
sleep in patients with insomnia. 9 , 10 It is a common problem with an
estimated prevalence in Europe of 6-12% of the adult population. 2
Insomnia as a disorder is quite different from a brief period of poor sleep,
and it can take its toll on both physical and mental health. 4 It is a
persistent condition with a negative impact on daytime functioning. 3 Idorsia’s
research has shown that poor quality sleep can affect many aspects of daily
life, including the ability to concentrate, mood, and energy levels.
The goal of treatments for insomnia is to improve sleep quality and quantity,
as well as daytime functioning, while avoiding adverse events and next-morning
residual effects. 5 Current recommended treatment of insomnia includes sleep
hygiene therapy, cognitive behavioral therapy, and pharmacotherapy. 6
About the orexin system
Wake and sleep signaling is regulated by intricate neural circuitry in the
brain. One key component of this process is the orexin system, which helps
promote wakefulness. 5 , 7 , 11 There are two forms of orexin neuropeptides –
small protein-like molecules used by nerve cells (neurons) to communicate with
each other in the brain – orexin A and orexin B. 7 Orexin promotes wakefulness
through its receptors OX1R and OX2R. 7 Together, these neuropeptides and
receptors make up the orexin system. The orexin system stimulates targeted
neurons in the wake system – leading to the release of several chemicals
(serotonin, histamine, acetylcholine, norepinephrine) – to promote wakefulness.
12 Under normal circumstances, orexin levels rise throughout the day as
wakefulness is promoted and then fall at night. 13 Overactivity of the wake
system is an important driver of insomnia. 5 , 10
The daridorexant Phase 3 registration program
The Phase 3 registration program comprised two three-month studies, together
with a long-term double-blind extension study. 1 The program enrolled a total
of 1,854 patients with insomnia disorder. 1 As insomnia often presents later in
life, and older adults are more susceptible to experience fragmented sleep,
early awakening and daytime sleepiness, 14 around 40% of the recruited
population was at least 65 years of age. 5
The placebo-controlled studies investigated the effects of three doses of
daridorexant (10 mg, 25 mg, and 50 mg) on sleep and daytime functioning
parameters, objectively in a sleep lab by polysomnography and subjectively with
a daily patient diary at home. 5 The impact of insomnia on patients’ daytime
functioning was measured daily using the sleepiness domain score from the
Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ © ) – a
patient-reported outcome (PRO) instrument developed and validated according to
the FDA Guidance for Industry. 5
More than 800 patients continued treatment in the 40-week extension study,
which measured the effect of all three doses vs. placebo, generating data for
long-term treatment of insomnia disorder. 15
Phase 3 data has been reported in The Lancet Neurology: The pivotal studies
demonstrated that daridorexant 50 mg significantly improved sleep onset, sleep
maintenance and self-reported total sleep time at months one and three compared
to placebo. 5 The largest effect was observed with the highest dose (50 mg),
followed by 25 mg, while the 10 mg dose did not have a significant effect. 5 In
all treatment groups the proportions of sleep stages were preserved, in
contrast to findings reported with benzodiazepine receptor agonists. 5
A major focus of the trials was to evaluate the impact of daridorexant on
daytime functioning in patients with insomnia disorder, as assessed by the
IDSIQ. 5 IDSIQ is a patient-reported outcomes instrument specifically developed
and validated according to FDA guidelines, to measure daytime functioning in
patients with insomnia. 16 The sleepiness domain score of the IDSIQ was
evaluated as a key secondary endpoint in both pivotal studies and comparisons
to placebo included type I error control for multiplicity. 5 Daridorexant 50 mg
demonstrated highly statistically significant improvement in daytime sleepiness
at month one and month three. 5 The sleepiness domain score was not
significantly improved on 25 mg in either study at either timepoint. 5
The overall incidence of adverse events was comparable between treatment
groups. 1 The most frequently reported adverse reactions were headache and
somnolence and, overall, the majority of adverse reactions were mild to
moderate in intensity. 1 There was no evidence of dose-dependent increases in
adverse events across the dosing range. 1 Further, no dependence, rebound
insomnia or evidence of abuse or withdrawal symptoms indicative of physical
dependence upon treatment discontinuation was observed in clinical studies. 1
Additional monitoring for QUVIVIQ™ ▼ (daridorexant)
▼ As a new medicinal product containing a new active substance, this medicinal
product is subject to additional monitoring, and it is therefore important to
report any suspected adverse events related to this medicinal product. Adverse
events should be reported. Healthcare professionals are asked to report any
suspected adverse reactions via the national reporting system .
Contraindications Hypersensitivity to daridorexant or any of the excipients
Narcolepsy Concomitant use with strong CYP3A4 inhibitors
Warnings and precautions for use
Use with caution in elderly patients because of the general risk of falls.
Efficacy and safety data in patients >75 are limited.
Patients should be cautioned about drinking alcohol during treatment.
Sleep paralysis and hypnagogic/hypnopompic hallucinations can occur, mainly
during the first weeks of treatment. Symptoms similar to mild cataplexy have
been reported with dual orexin receptor antagonists. Prescribers should explain
this to patients and should consider discontinuing in case events occur.
Use with caution in patients exhibiting symptoms of depression.
Use with caution in patients with psychiatric co-morbidities due to limited
efficacy and safety data.
Daridorexant did not have significant respiratory effects in patients with
mild or moderate OSA or moderate COPD. In the absence of data, use with caution
in patients with severe OSA and severe COPD.
There was no evidence of abuse or withdrawal symptoms indicative of physical
dependence upon treatment discontinuation in clinical studies with daridorexant
in subjects with insomnia. Because individuals with a history of abuse or
addiction to alcohol or other substances may be at increased risk for abuse of
QUVIVIQ, these patients should be followed carefully.
Use is not recommended in patients with severe hepatic impairment.
Effects on availability to drive and use machines
Patients should be cautioned about engaging in potentially hazardous
activities, driving, or operating heavy machinery unless they feel fully alert,
especially in the first few days of treatment. In order to minimize this risk,
a period of approximately 9 hours is recommended between taking QUVIVIQ and
driving or using machines.
About Professor Damien Léger
Professor Damien Léger, M.D, Ph.D. is the Head of the University Hospital
Hôtel Dieu, APHP, Sleep and Vigilance Center in Paris, France. He is also
Professor of Medicine at the Université Paris Cité. His primary research
interests focus on the impact of sleep disorders on public health, and he
serves as a consultant to the World Health Organization, the European Council,
the European Department of Mobility, French National Health Agency and the
French Ministry of Labor, Health, Transportation, Education and Environment,
advising these institutions on the influence of environmental factors such as
light, noise, shift and night work and work conditions on sleep and alertness.
Professor Léger was President of the French Sleep Research and Medicine Society
from 2017 to 2019, President of the French Institute of Sleep and Vigilance
from 2010 to 2015 and is a member of the European Board of the European
Insomnia Network. He is the author of eight books and over 220 scientific
publications. Professor Léger serves as a consultant to Idorsia.
1 QUVIVIQ TM Summary of Product Characteristics. 2022.
2 Riemann, D., et al. Sleep. 2017;26(6):675-700.
3 The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5;
American Psychiatric Association, 2013).
4 Wardle-Pinkston S., et al. Sleep Med Rev. 2019;48.
5 Mignot, E., et al. Lancet Neurol. 2022;21:125–39.
6 Muehlan, C., et al. Expert Opin. Drug Metab. Toxicol. 2020;16(11):1063–1078.
7 Muehlan, C., et al. J Psychopharmacol. 2020;34(3):326-335.
8 QUVIVIQ Prescribing Information. Idorsia Pharmaceuticals US Inc. Jan 2022.
9 Buysse, D.J., et al. Drug Discov Today Dis Models. 2011;8(4):129-137.
10 Levenson, J.C., et al. Chest. 2015;147(4):1179-1192.
11 Boof, M.L., et al. Eur J Clin Pharmacol. 2019;75(2):195-205.
12 Clifford, B.S., et al. Trends Neurosci. 2001;24(12).726-31.
13 Gotter, A.L., et al. BMC Neuroscience. 2013;14(1):14-19.
14 Patel, D., et al. J Clin Sleep Med. 2018;14(06):1017–1024.
15 Data on file, Idorsia.
16 Hudgens, S., et al. Patient. 2020. doi:10.1007/s40271-020-00474-z.
IDSIQ © 2020, University of Pittsburg. All rights reserved. IDSIQ-14
derivative created 2020 by Idorsia Pharmaceuticals Ltd under license and
distributed by Idorsia Pharmaceuticals Ltd under license. IDSIQ is further a
registered trademark of Idorsia Pharmaceuticals Ltd.
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Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is
specialized in the discovery, development and commercialization of small
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Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June
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For further information, please contact
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