^Allschwil, Switzerland - October 23, 2023
Idorsia Ltd (SIX: IDIA) today announced that it is committed to further the
science of sleep with a symposium and poster presentations at World Sleep 2023,
a global scientific congress bringing the best of sleep medicine and research to
Rio de Janeiro, Brazil, October 20-25.
An Industry Symposium entitled "Managing chronic insomnia disorder - what have
we learned from clinical trials and real-world practice?" will be hosted by
Idorsia on Tuesday, October 24, 12:30-14:00 BRT, Room 37, 3(rd) floor.
Antonio Olivieri, Senior Vice President, Head of Global Medical Affairs of
Idorsia, commented:
"Chronic insomnia disorder is a distinct disease characterized by difficulty
initiating or maintaining sleep, as well as impaired daytime functioning and is
associated with significant acute and long-term medical consequences. Overactive
wake signaling in the brain, promoted by the orexin system, is thought to be one
of the key factors causing chronic insomnia disorder. The orexin system
therefore provides a specific target for therapeutic intervention. In this
symposium, key learnings will be presented both from clinical studies and real-
world experience with daridorexant, Idorsia's dual orexin receptor antagonist."
In addition to the symposium, the following posters are being presented at World
Sleep 2023:
* Di Marco T., et al. Effect of daridorexant on sleep micro-architecture in
adult patients with insomnia disorder - An analysis of two pooled Phase 3
studies [Poster #070]
* Saskin P., et al. Real World Evidence of adverse events of prescribed
medications for insomnia [Poster #090]
* Boof M.-L., ?Repeated dosing (5 nights) of 50 mg daridorexant in patients
with severe obstructive sleep apnea: Effect on sleep-disordered breathing
and sleep???? [Poster #187]
* Lettieri C.J., et al. The Effects of Daridorexant 50 mg on Patients with
Comorbid Insomnia Disorder and Untreated Mild Obstructive Sleep Apnea: A
Subgroup Post-hoc Analysis of a Phase 3 Clinical Trial [Poster #209]
Furthermore, the following posters on the real-world experience with
daridorexant are being presented independently by three research groups:
* Fernandes M., et al. Daridorexant treatment effectiveness for chronic
insomnia: A real-world retrospective study [Poster #075]
* Palagini L., et al. Early experience with the new DORA daridorexant in
patients with insomnia disorder: results of a real world study with a 3
months follow up period [Poster #085]
* Winter Y., et al. Influence of daridorexant on the health-related quality of
life in patients with chronic insomnia [Poster #096]
The abstracts can be found in the Scientific Program for World Sleep 2023
(https://worldsleepcongress.com/program).
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.(2) 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.(2)
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.(7)(,)(8) Chronic insomnia is a common problem with an
estimated prevalence in Switzerland of 9.2% of the working-age population.(14)
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.(2)(,)(3) It is a
persistent condition with a negative impact on daytime functioning.(2) 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. Current recommended treatment of insomnia includes sleep
hygiene therapy, cognitive behavioral therapy, and pharmacotherapy.
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.(6)(,)(9) 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.(5)(,)(6) Orexin promotes
wakefulness through its receptors OX1R and OX2R.(5)(,)(6) 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.(10) Under normal circumstances, orexin levels rise
throughout the day as wakefulness is promoted and then fall at night.(11)
Overactivity of the wake system is an important driver of insomnia.(4)(,)(9)
Idorsia's research team has been working on the science of orexin and orexin
receptors since they were first described in 1998. The team's initial work led
to the conclusion that antagonism of the orexin system was the key to preserving
a natural sleep architecture for patients with insomnia. With this as the
target, the team designed dual antagonists with the goal of rapid onset of
effect and duration of action sufficient to cover the night but short enough to
minimize any negative next-morning residual activity at optimally effective
doses.
About 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.(5) Chronic insomnia disorder
is the result of continued brain hyperarousal that requires sustained management
with therapy suitable for daily use over months.(6) Orexin is a neuropeptide, a
small protein-like molecule, produced by the brain that promotes wakefulness.(5)
Daridorexant reduces nocturnal hyperarousal to improve sleep (onset and
maintenance) without next-morning residual effects in insomnia patients, and
thus improves daytime functioning.(4)
Global regulatory status of daridorexant
In January 2022, daridorexant was approved by the US Food and Drug
Administration (FDA). In April 2022, marketing authorization of daridorexant was
granted by the European Commission and subsequently by the Medicines and
Healthcare products Regulatory Agency (MHRA) in Great Britain via the European
Commission Decision Reliance Procedure. Marketing authorization of daridorexant
was granted by Swissmedic in December 2022. In April 2023, Health Canada
approved daridorexant in Canada.
The daridorexant Phase 3 registration program(4)
The Phase 3 registration program comprised two three-month studies, together
with a long-term double-blind extension study. The program enrolled a total of
1,854 patients with insomnia disorder. As insomnia often presents later in life,
and older adults are more susceptible to experience fragmented sleep, early
awakening and daytime sleepiness,(12) around 40% of the recruited population was
at least 65 years of age.(15)
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. 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.
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.(16)
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. 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. In
all treatment groups the proportions of sleep stages were preserved, in contrast
to findings reported with benzodiazepine receptor agonists.
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. IDSIQ is a patient-reported outcomes instrument specifically developed
and validated according to FDA guidelines, to measure daytime functioning in
patients with insomnia.(1)(3) 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. Daridorexant 50 mg
demonstrated highly statistically significant improvement in daytime sleepiness
at month one and month three. The sleepiness domain score was not significantly
improved on 25 mg in either study at either timepoint.
The overall incidence of adverse events was comparable between treatment groups.
The most frequently reported adverse reactions were headache and somnolence and,
overall, the majority of adverse reactions were mild to moderate in intensity.
No evidence of a dose-relationship for the frequency or severity of adverse
reactions was observed.
References
1. Riemann, D., et al. Sleep. 2017;26(6):675-700.
2. The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5;
American Psychiatric Association, 2013).
3. Wardle-Pinkston S., et al. Sleep Med Rev. 2019;48.
4. Mignot, E., et al. Lancet Neurol. 2022;21:125-39.
5. Muehlan, C., et al. Expert Opin. Drug Metab. Toxicol.
2020;16(11):1063-1078.
6. Muehlan, C., et al. J Psychopharmacol. 2020;34(3):326-335.
7. Buysse, D.J., et al. Drug Discov Today Dis Models. 2011;8(4):129-137.
8. Levenson, J.C., et al. Chest. 2015;147(4):1179-1192.
9. Boof, M.L., et al. Eur J Clin Pharmacol. 2019;75(2):195-205.
10. Clifford, B.S., et al. Trends Neurosci. 2001;24(12).726-31.
11. Gotter, A.L., et al. BMC Neuroscience. 2013;14(1):14-19.
12. Patel, D., et al. J Clin Sleep Med. 2018;14(06):1017-1024.
13. Hudgens, S., et al. Patient. 2020. doi:10.1007/s40271-020-00474-z.
14. Hafner, M., et al. The Societal and Economic Burden of Insomnia in Adults:
An International Study. Santa Monica, CA: RAND Corporation, 2023.
15. Fietze I., et al. 2022 Oct;39(10):795-810.
16. Kunz D, et al. CNS Drugs. 2022 Dec 9.
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.
About Idorsia
Idorsia Ltd is reaching out for more - We have more ideas, we see more
opportunities and we want to help more patients. In order to achieve this, we
will develop Idorsia into a leading biopharmaceutical company, with a strong
scientific core.
Headquartered near Basel, Switzerland - a European biotech-hub - Idorsia is
specialized in the discovery, development and commercialization of small
molecules to transform the horizon of therapeutic options. Idorsia has a 20-year
heritage of drug discovery, a broad portfolio of innovative drugs in the
pipeline, an experienced team of professionals covering all disciplines from
bench to bedside, and commercial operations in Europe and North America - the
ideal constellation for bringing innovative medicines to patients.
Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017
and has over 1,200 highly qualified specialists dedicated to realizing our
ambitious targets.
For further information, please contact
Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil
+41 58 844 10 10
investor.relations@idorsia.com
media.relations@idorsia.com
www.idorsia.com (http://www.idorsia.com)
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with respect to future events and are subject to certain risks, uncertainties
and assumptions. Many factors could cause the actual results, performance or
achievements of the company to be materially different from any future results,
performances or achievements that may be expressed or implied by such forward-
looking statements. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect, actual results
may vary materially from those described herein as anticipated, believed,
estimated or expected.
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