WKN: | A2DTEB |
ISIN: | CH0363463438 |
Land: | Schweiz |
Branche: | Chemie, Pharma, Bio- und Medizintechnik |
Sektor: | Pharma |
aktueller Kurs: |
2,73 EUR
|
Veränderung: |
0,12 EUR
|
Veränderung in %: |
4,40 %
|
Notes to the editor About insomnia
Insomnia is a condition of overactive wake signaling that can have a profound effect on the lives of patients. Insomnia can be defined as difficulty falling asleep and / or staying asleep, occuring at least three times a week for a minimum of three months. It is estimated that as many as one in ten people suffer from insomnia and its impact is often underestimated. In reality, it can be a distressing condition that can impair quality of life. Sleepless nights can leave people feeling irritable and out of sorts – this may affect many aspects of daily life, from studying and employment to social activities and relationships. People who suffer from insomnia may lack the energy or motivation to exercise or to take part in social activities. It can also have a significant economic impact as it increases the risk of accident and injury on the road or in the workplace, and is a leading cause of absenteeism and reduced productivity at work. People with insomnia are more likely to experience feeling down or depressed, lack concentration, and suffer from poor energy levels during the day compared with people who sleep well. In addition, worrying about sleep can cause stress and may lead to negative thought patterns which may in turn make it more difficult to sleep, setting up a vicious circle. Chronic insomnia is associated with cardiovascular and cerebrovascular diseases, and increased mortality. The goal of treatments for insomnia is to improve sleep quality and quantity, as well as reducing insomnia-related impaired daytime functioning, while avoiding adverse events and next morning residual effect. Current treatment of insomnia includes cognitive behavioral therapy, sleep hygiene recommendations, and pharmacotherapy. The most widely prescribed products on the market that are indicated for insomnia enhance the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Such medications are only approved for short-term use and are associated with side effects such as next-morning residual effects, anterograde amnesia, and risk of tolerance and dependence. 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 and consolidate wakefulness. There are two forms of orexin neuropeptides – Orexin A and Orexin B. Orexin promotes wakefulness through its receptors OX1R and OX2R. In combination, these neuropeptides and receptors comprise the orexin system. The orexin system stimulates target neurons in the wake system – leading to the release of several chemicals (Dopamine, Serotonin, Histamine, Acetylcholine, Norepinephrine) which promote wakefulness. Under normal circumstances, orexin levels rise throughout the day as wakefulness is promoted and then consolidated and fall at night. Overactivity of the orexin system is thought to be an important driver of insomnia. Idorsia’s research team has been working on the science of orexin and orexin receptors since they were first described in 1998. The teams 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 started to design a dual antagonist with a rapid effect, and a duration of action sufficient for the night but short enough to avoid any negative residual activity the following morning at optimally effective doses. About dual orexin receptor antagonism
Dual orexin receptor antagonists – or DORAs – are an entirely different approach to treating insomnia than previous drug classes, turning down overactive wakefulness by blocking the activity of orexin. DORAs specifically target the orexin system by competitively binding with both receptors and thereby reversibly blocking the activity of orexin. It is hypothesized that blocking orexin receptors reduces the downstream activity of the other wake promoting neurotransmitters that are overactive in insomnia, leading to the clinical efficacy demonstrated by orexin receptor antagonists. Data supporting daridorexant in insomnia
Results of the first Phase 3 study, investigating daridorexant doses 25 and 50mg, were reported in April 2020. The study demonstrated efficacy of treatment with daridorexant on objective and subjective sleep parameters and daytime functoning with no residual effect in the morning, and no evidence of rebound or withdrawal symptoms upon treatment discontinuation. Daridorexant at both 25 and 50 mg significantly improved sleep onset and sleep maintenance as measured objectively in a sleep lab by polysomnography. Daridorexant also significantly improved subjective total sleep time as measured daily with a patient diary at home. The results were consistently statistically significant at month 1 and at month 3, indicating sustained benefit. Furthermore, treatment with daridorexant improved patients’ daytime functioning from baseline at month 1 and month 3. The rate of adverse events was comparable between placebo and daridorexant at both treatment doses. Treatment-emergent adverse events (TEAEs) during the double-blind study period were reported in 37.7% and 37.7% of the patients treated with 25 and 50 mg daridorexant, respectively (34.0% for placebo). The most frequent TEAE reported over 3% incidence and higher than placebo was nasopharyngitis, headache. Prior to the Phase 3 program, the safety and efficacy of daridorexant in adult and elderly patients with insomnia was evaluated in a comprehensive Phase 2 program, comprising two studies, one of which included zolpidem 10 mg as an active reference. Both studies showed the desired effect on sleep maintenance and onset, with a significant dose-response relationship; treatment was generally well tolerated. A comprehensive clinical pharmacology program is being conducted totaling approximately 20 studies and including, amongst others, studies assessing abuse liability, drug-drug interactions, next-morning driving, the effect of daridorexant on respiratory function in patients with chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA), and the pharmacokinetics of daridorexant in patients with liver and renal impairment. Emmanuel Mignot, MD and Professor of Psychiatry and Behavioral Sciences at Stanford University
He is a former student of the Ecole Normale Superieure (Ulm, Paris, France) and received his M.D. and Ph.D. from Paris V and VI University in France. He practiced medicine in France for several years before joining Stanford as a faculty member in 1991 and was named Director of the Stanford Center for Narcolepsy in 1993. Dr. Mignot was named the Craig Reynolds Professor of Psychiatry and Behavioral Sciences in 2001. He served as the Director of the Stanford Center of Sleep Sciences and Medicine from 2009 to 2019. Dr. Mignot is internationally recognized for discovering the cause of narcolepsy. His findings led to the development of new hypnotics that block the hypocretin (orexin) receptor and is likely to have other therapeutic applications as well. His research also demonstrated that narcolepsy is a selective autoimmune disease of the hypocretin system showing the involvement of molecular mimicry in humans with influenza A. He has received numerous research grants and honors including National Sleep Foundation and National Institute of Health Research Awards, Howard Hughes Medical Institute Investigator and McKnight Neuroscience awards, the Narcolepsy Network professional service award, the Drs. C. and F. Demuth 11th Award for Young Investigators in the Neurosciences, the WC Dement Academic Achievement Award in sleep disorders medicine, the CINP and ACNP awards in neuropharmacology and the Jacobaeus prize. Dr. Mignot is an elected member of the Association of American Physicians, the Institute of Medicine, and of the National Academy of Sciences (USA). He is the co-author of more than 200 original scientific publications, and he serves on the editorial board of scientific journals in the field of sleep and biology research. Dr. Mignot is an active member of several professional and governmental organizations. He has served as President of the Sleep Research Society, Chair of the National Center on Sleep Disorders Research Advisory board of the National institutes of Health, and Chair of the Board of Scientific Counselors of the National Institute of Mental Health. Most of Dr. Mignot's current research focuses on the neurobiology, genetics and immunology of narcolepsy, a disorder caused by hypocretin (orexin) cell loss, with indirect interest in the neuroimmunology of other brain disorders. His laboratory uses state of the art human genetics techniques, such as genome wide association, exome or whole genome sequencing in the study of human sleep and sleep disorders, with parallel studies in animal models. His laboratory is also interested in web-based assessments of sleep disorders, computer-based processing of polysomnography (PSG), and outcomes research. Dr. Mignot serves as a consultant to Idorsia. References
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