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Current Drug Research Reviews

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ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

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Daridorexant, a Recently Approved Dual Orexin Receptor Antagonists (DORA) in the Treatment of Insomnia

Author(s): Dwaipayan S. Chakraborty*, Shouvik Choudhury and Sandeep Lahiry

Volume 15, Issue 2, 2023

Published on: 21 December, 2022

Page: [149 - 158] Pages: 10

DOI: 10.2174/2589977515666221108093830

Price: $65

Abstract

Insomnia is one of the major challenges in medical science nowadays as it leads to the great socio-economic burden by impairing daytime function as well as the development of exhaustion, depression and memory disturbance in affected individuals. Several important classes of drugs have been tried including the BZDs and Non-BZD hypnotics. Available drugs to combat this disease have the limitations of abuse potential, tolerance and cognitive impairments. In some instances, withdrawal symptoms have been observed on abrupt cessation of those drugs. The Orexin system has been very recently targeted as a therapeutic option to overcome those limitations. Daridorexant as a Dual Orexin Receptor Antagonists (DORA) in the treatment of insomnia has been evaluated in several preclinical and clinical studies. Available information obtained from those studies has shown promising future for this drug in the management of insomnia. Beyond its effectiveness in insomnia, it has been successfully used in patients suffering from Obstructive sleep apnoea, Chronic Obstructive Airway Disease (COAD), Alzheimer’s Disease (AD), hypertension and cardiovascular disorders. Larger studies need to address the safety issues as well as obtain robust pharmacovigilance information to safeguard the risk-benefit aspect of this drug in insomniac adults.

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[1]
Roth T, Coulouvrat C, Hajak G, 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: 592-60.
[2]
Hudgens S, Phillips-Beyer A, Newton L, Seboek Kinter D, Benes H. development and validation of the insomnia daytime symptoms and impacts questionnaire. IDSIQ 2020.
[3]
Wilson S, Anderson K, Baldwin D, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: An update. J Psychopharmacol 2019; 33(8): 923-47.
[http://dx.doi.org/10.1177/0269881119855343] [PMID: 31271339]
[4]
Chieffi S, Carotenuto M, Monda V, et al. Orexin system: The key for a healthy life. Front Physiol 2017; 8: 357.
[http://dx.doi.org/10.3389/fphys.2017.00357] [PMID: 28620314]
[5]
Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron 2017; 93(4): 747-65.
[http://dx.doi.org/10.1016/j.neuron.2017.01.014]
[6]
Barson JR, Leibowitz SF. Orexin/hypocretin system: Role in food and drug overconsumption. Int Rev Neurobiol 2017; 136: 199-237.
[http://dx.doi.org/10.1016/bs.irn.2017.06.006] [PMID: 29056152]
[7]
Willie JT, Chemelli RM, Sinton CM, et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: Molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 2003; 38(5): 715-30.
[http://dx.doi.org/10.1016/S0896-6273(03)00330-1] [PMID: 12797957]
[8]
Beuckmann CT, Suzuki M, Ueno T, Nagaoka K, Arai T, Higashiyama H. In vitro and in silico characterization of lemborexant (E2006), a novel dual orexin receptor antagonist. J Pharmacol Exp Ther 2017; 362(2): 287-95.
[http://dx.doi.org/10.1124/jpet.117.241422] [PMID: 28559480]
[9]
Janto K, Prichard JR, Pusalavidyasagar S. An update on dual orexin receptor antagonists and their potential role in insomnia therapeutics. J Clin Sleep Med 2018; 14(8): 1399-408.
[http://dx.doi.org/10.5664/jcsm.7282] [PMID: 30092886]
[10]
Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD. Clinical Guidelines Committee of the American College of Physicians. Man-agement of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2016; 165(2): 125-33.
[http://dx.doi.org/10.7326/M15-2175] [PMID: 27136449]
[11]
Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2017; 13(2): 307-49.
[http://dx.doi.org/10.5664/jcsm.6470] [PMID: 27998379]
[12]
ClinCalc.com. The Top 200 Drugs of 2019. 2019. Available from: https://clincalc.com/DrugStats/
[13]
Frey DJ, Ortega JD, Wiseman C, Farley CT, Wright KP Jr. Influence of zolpidem and sleep inertia on balance and cognition during nighttime awakening: a randomized placebo-controlled trial. J Am Geriatr Soc 2011; 59(1): 73-81.
[http://dx.doi.org/10.1111/j.1532-5415.2010.03229.x] [PMID: 21226678]
[14]
Rosenberg RP. Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies. Ann Clin Psychiatry 2006; 18(1): 49-56.
[http://dx.doi.org/10.1080/10401230500464711] [PMID: 16517453]
[15]
US Food and Drug Administration. FDA adds boxed warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines Available from: https://www.fda. gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-
[16]
Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 2008; 4(5): 487-504.
[http://dx.doi.org/10.5664/jcsm.27286] [PMID: 18853708]
[17]
Lee MG, Hassani OK, Jones BE. Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 2005; 25(28): 6716-20.
[http://dx.doi.org/10.1523/JNEUROSCI.1887-05.2005] [PMID: 16014733]
[18]
Gotter AL, Winrow CJ, Brunner J, et al. The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold. BMC Neurosci 2013; 14(1): 90.
[http://dx.doi.org/10.1186/1471-2202-14-90] [PMID: 23981345]
[19]
Clark JW, Brian ML, Drummond SPA, Hoyer D, Jacobson LH. Effects of orexin receptor antagonism on human sleep architecture: A systematic review. Sleep Med Rev 2020; 53: 101332.
[http://dx.doi.org/10.1016/j.smrv.2020.101332] [PMID: 32505969]
[20]
Snyder E, Ma J, Svetnik V, et al. Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data. Sleep Med 2016; 19: 93-100.
[http://dx.doi.org/10.1016/j.sleep.2015.10.007] [PMID: 27198953]
[21]
Moline M, Zammit G, Cheng JY, Perdomo C, Kumar D, Mayleben D. Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder. J Clin Sleep Med 2021; 17(6): 1167-74.
[http://dx.doi.org/10.5664/jcsm.9150] [PMID: 33590823]
[22]
Herring WJ, Connor KM, Ivgy-May N, et al. Suvorexant in patients with insomnia: Results from two 3-month randomized controlled clinical trials. Biol Psychiatry 2016; 79(2): 136-48.
[http://dx.doi.org/10.1016/j.biopsych.2014.10.003] [PMID: 25526970]
[23]
Michelson D, Snyder E, Paradis E, et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: A phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol 2014; 13(5): 461-71.
[http://dx.doi.org/10.1016/S1474-4422(14)70053-5] [PMID: 24680372]
[24]
Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant with placebo and zolpidem tartrate extended release for the treatment of older adults with insomnia disorder: A phase 3 randomized clinical trial. JAMA Netw Open 2019; 2(12): e1918254.
[http://dx.doi.org/10.1001/jamanetworkopen.2019.18254] [PMID: 31880796]
[25]
Treiber A, de Kanter R, Roch C, et al. The use of physiology-based pharmacokinetic and pharmacodynamic modeling in the discovery of the dual orexin receptor antagonist ACT-541468. J Pharmacol Exp Ther 2017; 362(3): 489-503.
[http://dx.doi.org/10.1124/jpet.117.241596] [PMID: 28663311]
[26]
Boss C, Gatfield J, Brotschi C, et al. The quest for the best dual orexin receptor antagonist (daridorexant) for the treatment of insomnia disorders. ChemMedChem 2020; 15(23): 2286-305.
[http://dx.doi.org/10.1002/cmdc.202000453] [PMID: 32937014]
[27]
Markham A. Daridorexant: First approval. Drugs 2022; 82(5): 601-7.
[http://dx.doi.org/10.1007/s40265-022-01699-y] [PMID: 35298826]
[28]
Grandjean Celia Mueller, Kiry Manon, Vaillant Catherine, Nayler Oliver, Gatfield John. 059 Daridorexant: A dual, equipotent, and insurmountable antagonist of both orexin-1 and orexin-2 receptors. Sleep 2021; 44 (Supplement_2): A25.
[29]
NDA approval of Quviviq (daridorexant) tablets. U.S. Food and Drug Administration.2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/214985Orig1s000ltr.pdf
[30]
Ufer M, Kelsh D, Schoedel KA, Dingemanse J. Abuse potential assessment of the new dual orexin receptor antagonist daridorexant in recreational sedative drug users as compared to suvorexant and zolpidem. Sleep 2022; 45(3): zsab224.
[http://dx.doi.org/10.1093/sleep/zsab224] [PMID: 34480579]
[31]
Steiner MA, Locher R, Lecourt H, Jenck F. W15. The novel insomnia drug daridorexant also reduces behavioral and physiological stress responses in rats. Neuropsychopharmacology 2020; 45: 286.
[32]
Dauvilliers Y, Zammit G, Fietze I, et al. Daridorexant, a new dual orexin receptor antagonist to treat insomnia disorder. Ann Neurol 2020; 87(3): 347-56.
[http://dx.doi.org/10.1002/ana.25680] [PMID: 31953863]
[33]
Roch C, Bergamini G, Steiner MA, Clozel M. Nonclinical pharmacology of daridorexant: A new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology (Berl) 2021; 238(10): 2693-708.
[http://dx.doi.org/10.1007/s00213-021-05954-0] [PMID: 34415378]
[34]
Zammit G, Dauvilliers Y, Pain S, Sebök Kinter D, Mansour Y, Kunz D. Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder. Neurology 2020; 94(21): e2222-32.
[http://dx.doi.org/10.1212/WNL.0000000000009475] [PMID: 32341187]
[35]
Idorsia Pharmaceuticals Ltd. Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia [press release]. Available from: https://www.idorsia.com/media/news-details? newsId=2284972. Accessed February 22, 2021.
[36]
Idorsia Pharmaceuticals Ltd. Idorsia announces positive results in the second Phase 3 study of daridorexant [press release]. Available from: https://www.idorsia.com/investors/news-and-events/media-releasedetails?newsId=2329316 Accessed February 22, 2021.
[37]
Idorsia Ltd. Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia [Press release]. 20 Apr 2020.
[38]
Boof ML, Dingemanse J, Brunke M, et al. Effect of the novel dual orexin receptor antagonist daridorexant on night‐time respiratory function and sleep in patients with moderate chronic obstructive pulmonary disease. J Sleep Res 2021; 30(4): e13248.
[http://dx.doi.org/10.1111/jsr.13248] [PMID: 33417730]
[39]
Boof ML, Dingemanse J, Lederer K, et al. Effect of the new dual orexin receptor antagonist daridorexant on nighttime respiratory function and sleep in patients with mild and moderate obstructive sleep apnea. Sleep (Basel) 2020; 44(6): zsaa275.
[http://dx.doi.org/10.1093/sleep/zsaa275] [PMID: 33305817]
[40]
Idorsia recieves US FDA approval of Quiviviq (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. 2022. Available from: https://www.biospace.com/article/releases/idorsia-receives-us-fdaapproval-of-quviviqdaridorexant-25-and-50-mg-for-the-treatment-ofadults-with-insomnia/?s=85
[41]
Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol 2022; 21(2): 125-39.
[http://dx.doi.org/10.1016/S1474-4422(21)00436-1] [PMID: 35065036]
[42]
Zammit G, Mayleben D, Fietze I, et al. Daridorexant improves total sleep time (TST). In insomnia patients without altering the proportion of sleep stages. Presented at SLEEP 2021 Annual Meeting. June 10- 13; 2021.
[43]
Li A, Hindmarch CCT, Nattie EE, Paton JFR. Antagonism of orexin receptors significantly lowers blood pressure in spontaneously hypertensive rats. J Physiol 2013; 591(17): 4237-48.
[http://dx.doi.org/10.1113/jphysiol.2013.256271] [PMID: 23671161]

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