Daridorexant: First Approval

Markham, Anthony

doi:10.1007/s40265-022-01699-y

Cited by 47 publications

(49 citation statements)

References 20 publications

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“…They inhibit a major wake-promoting pathway responsible for the overactive wake signalling (hyperarousal) characteristic of insomnia by blocking the binding of the orexin A and B neuropeptides to the two orexin receptors [30]. Daridorexant is a new potent, selective, dual orexin receptor antagonist approved for the treatment of insomnia in adults aged ≥ 18 years [31]. It has a favourable pharmacokinetic/pharmacodynamic profile with a rapid absorption enabling a fast sleep onset, and a rapid elimination, enabling sleep maintenance without next-morning sleepiness and no accumulation upon repeated nightly dosing [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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Background and ObjectiveThe dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults'). Methods Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, doubleblind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness. Results At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour. Conclusions In older patients with insomnia, as in younger patients, the effi...

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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“…Daridorexant was patented in 2013 and received its first approval for use in treating adult insomnia in the US on January 7, 2022. 45 It is available in 25 to 50 mg once daily oral doses. 46 Daridorexant's recommended administration is within 30 minutes of going to bed with at least 7 hours before planned awakening.…”

Section: Daridorexant Informationmentioning

confidence: 99%

“…45 It is available in 25 to 50 mg once daily oral doses. 46 Daridorexant's recommended administration is within 30 minutes of going to bed with at least 7 hours before planned awakening. Daridorexant was found to help patients fall asleep faster and stay asleep longer in comparison with a placebo, and 50 mg doses were found to be more effective and had longer-lasting effects than 25 mg doses.…”

Section: Daridorexant Informationmentioning

confidence: 99%

“…[52][53][54] MECHANISM OF ACTION OF DARIDOREXANT/ DARIDOREXANT DRUG INFO Daridorexant (Quviviq™) has been specifically developed to act on orexin receptors OX1 and OX2, and antagonize their effects, promoting sleep. 45 Daridorexant (ACT-541468) has been recently approved by the FDA for the treatment of insomnia and has been sub-grouped under a fairly novel class of drugs known as DORAs as it selectively and potently exhibits its effects on both OX1 and OX2 receptors. [55][56][57][58][59] Orexinergic neurons which are notably found in the hypothalamus have a well-connected system projecting their axons to several wake-promoting neuronal regions such as dorsal raphe, ventral tegmental area, locus ceruleus, tuberomammillary nuclei centers, and laterodorsal tegmental nuclei where the abundance of serotonergic, dopaminergic, noradrenergic, histaminergic, and cholinergic neuronal projections are found to exist.…”

Section: Daridorexant Informationmentioning

confidence: 99%

“…Daridorexant, classified as a DORA, was recently approved in January 2022 by the United States Food and Drug Administration (US FDA) for treating insomnia. [6][7][8] The purpose of this paper is to summarize the safety and efficacy of daridorexant in treating insomnia.…”

Section: Introductionmentioning

confidence: 99%

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Daridorexant for the Treatment of Insomnia

Robinson

Supra

Downs

et al. 2022

Health Psychology Research

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Purpose of Review Insomnia is a complex sleeping disorder that affects the lives of many individuals worldwide. Insomnia often occurs in the presence of coexisting comorbidities making it a complex disorder that requires a multifactorial approach to therapy. First-line therapy is cognitive-behavioral therapy for insomnia (CBT-I). Pharmacotherapy for insomnia falls into four classes based on mechanism of action: benzodiazepine receptor agonists (BZRAs), histamine receptor antagonists, melatonin receptor agonists, and dual orexin receptor antagonists (DORAs). Recent Findings Daridorexant is a dual orexin type 1 and types 2 (OX1 and OX2) receptor antagonist that was recently approved by the US FDA for the treatment of adults suffering from insomnia. It was shown to be effective in reducing insomnia symptoms, increasing daytime functioning, and improving the overall quality of sleep. Daridorexant offers patients relief from insomnia while avoiding the severe side effects and dependency issues of traditional treatments like benzodiazepines and sedatives. Summary In this article, we review the most recent data on insomnia treatments and summarize the safety and efficacy of daridorexant in treating insomnia.

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New drug approvals for 2022: Synthesis and clinical applications

Yuan

Shen

Jia

et al. 2023

Medicinal Research Reviews

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The U.S. Food and Drug Administration has approved a total of 37 new drugs in 2022, which are composed of 20 chemical entities and 17 biologics. In particular, 20 chemical entities, including 17 small molecule drugs, 1 radiotherapy, and 2 diagnostic agents, provide privileged scaffolds, breakthrough clinical benefits, and a new mechanism of action for the discovery of more potent clinical candidates. The structure‐based drug development with clear targets and fragment‐based drug development with privileged scaffolds have always been the important modules in the field of drug discovery, which could easily bypass the patent protection and bring about improved biological activity. Therefore, we summarized the relevant valuable information about clinical application, mechanism of action, and chemical synthesis of 17 newly approved small molecule drugs in 2022. We hope this timely and comprehensive review could bring about creative and elegant inspiration on the synthetic methodologies and mechanism of action for the discovery of new drugs with novel chemical scaffolds and extended clinical indications.

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Daridorexant: First Approval

Cited by 47 publications

References 20 publications

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

Daridorexant for the Treatment of Insomnia

New drug approvals for 2022: Synthesis and clinical applications

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