LONDON, Sept. 15, 2023 /PRNewswire/ -- Idorsia UK Ltd today announced that the National Institute for Health and Care Excellence (NICE) has issued Final Draft Guidance (FDG) recommending QUVIVIQ™▼ (daridorexant) for treating insomnia in adults with symptoms lasting for three nights or more per week for at least three months, and whose daytime functioning is considerably affected, only if cognitive behavioural therapy for insomnia (CBTi) has been tried but not worked, or CBTi is not available or is unsuitable.¹ NICE recommends that the length of treatment with daridorexant should be as short as possible.¹ Treatment should be assessed within three months of starting and should be stopped in people whose chronic insomnia has not responded adequately. If treatment with daridorexant is continued, it should be assessed at regular intervals to determine whether it is still working.¹

Following the anticipated publication of NICE's final technology appraisal, daridorexant will become the first dual orexin receptor antagonist (DORA) available for prescription on the NHS in England and Wales.

Dr David O'Regan, Consultant in Psychiatry and Sleep Medicine, London, commented: 
"Today's announcement by NICE represents a significant breakthrough for chronic insomnia patients. While other treatment options for insomnia are available, these may not be suitable for long-term use, effective for all patients or specifically licensed for the treatment of chronic insomnia. It's very encouraging that NICE has made this recommendation, and in doing so recognise the importance of new innovations to help patients manage this life-changing condition."

Chronic insomnia occurs when the impact on sleep quantity or quality is present for at least three nights per week, lasts for at least three months, and occurs despite an adequate opportunity to sleep.^6,7 Idorsia estimates that chronic insomnia affects around 7% of the UK adult population.⁵ A key symptom of chronic insomnia is the impairment of daytime functioning,^6,7 which is linked to significant reductions in health status, such as fatigue, reduced energy, mood alteration and cognitive difficulties.⁸ Furthermore, suboptimal management of this condition is associated with decreased workplace productivity,⁹ and increased risk of workplace accidents, falls, and costly workplace errors.^10,11,12

Wake and sleep signaling is regulated by intricate neural activity in the brain.¹³ One key component of this process is the orexin system, which helps promote wakefulness.¹⁴ Currently, the most commonly prescribed medications for insomnia induce sleep through broad inhibition of brain activity, and can be associated with patients developing dependency, or experiencing next-morning residual effects (grogginess).^3,15 Daridorexant works differently by selectively blocking only the activation of orexin receptors, thereby directly targeting the mechanism that controls overactive wakefulness.^2,3 In clinical studies, after 12 months of treatment, daridorexant was not associated with physical signs of dependency, tolerance or rebound insomnia after it's discontinuation.^4,16

Lisa Artis, Deputy CEO, The Sleep Charity UK, commented: 
"While we all may experience short periods of sleeplessness, people living with chronic insomnia are persistently deprived of the restorative sleep they need, which can have a major impact on their overall health and wellbeing. Today's announcement from NICE will come as welcome news for patients by making available a suitable new treatment option."

Robert Moore, General Manager of Idorsia UK, commented:
"Today's positive NICE recommendation of daridorexant is a landmark moment for both patients and clinicians. We are delighted that NICE has acknowledged the clinical benefits and value that this new treatment can offer to the eligible patient population with chronic insomnia. The improvement of daytime functioning should be a priority for patients with chronic insomnia as the disorder has a significant impact on workplace productivity and overall wellbeing. Daridorexant is the result of over 20 years of research, and we are incredibly proud that NHS patients in England and Wales will soon be able to access this innovative new treatment."

Daridorexant received marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain in August 2022 under the European Commission Decision Reliance Procedure, for the treatment of adult patients with insomnia characterised by symptoms present for at least three months and considerable impact on daytime functioning.⁴

This decision was based on evidence from two pivotal Phase 3 studies that evaluated the efficacy and safety of daridorexant in patients with insomnia disorder.³ These studies demonstrated that at the recommended dose, daridorexant improved sleep onset, sleep maintenance, sTST and daytime sleepiness in adults with insomnia disorder at months one and three compared to placebo.^3,4

The MHRA also considered the results of a long-term follow-up extension study, which together with the pivotal trials, provided clinical data for up to 12 months of continuous treatment.^4,16

Notes to the editor

About chronic insomnia 
Insomnia is defined as difficulty initiating or maintaining sleep, causing clinically significant distress or impairment in important areas of daytime functioning.⁷ Chronic insomnia occurs when the impact on sleep quantity or quality is present for at least three nights per week, lasts for at least three months, and occurs despite an adequate opportunity to sleep.⁷ 

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.^17,18

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.¹⁹ It is a persistent condition with a negative impact on daytime functioning.⁷ Poor quality sleep can affect many aspects of daily life, including the ability to concentrate, mood, and energy levels.⁸ 

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.³ Current recommended treatment of insomnia includes sleep hygiene therapy, cognitive behavioural therapy, and pharmacotherapy.²⁰

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.^3,14,21 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.²⁰ Orexin promotes wakefulness through its receptors OX1R and OX2R.²⁰ 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.²² Under normal circumstances, orexin levels rise throughout the day as wakefulness is promoted and then fall at night.²³ Overactivity of the wake system is an important driver of insomnia.^3,17 

Daridorexant dosing information
The recommended dose of daridorexant is one tablet of 50 mg once per night, taken orally in the evening within 30 minutes before going to bed.⁴ 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 night.⁴ 

Additional monitoring for QUVIVIQ™▼ (daridorexant) 
For more information on the marketing authorisation of QUVIVIQ in Great Britain, please review the Summary of Product Characteristics (SmPC) which can be found on https://products.mhra.gov.uk

▼ 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 Yellow Card at https://yellowcard.mhra.gov.uk/.

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 daridorexant, 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 minimise this risk, a period of approximately 9 hours is recommended between taking daridorexant and driving or using machines.

Further information on the warnings and precautions for use can be found in the SmPC on https://products.mhra.gov.uk or in the Patient Information Leaflet.

References

¹ NICE. Final Draft Guidance. Daridorexant for treating long-term insomnia. 2023. Available at: https://www.nice.org.uk/guidance/gid-ta10888/documents/674.
² Roch, C, et al. Psychopharmacology. 2021;238(10):2693–2708.
³ Mignot, E, et al. Lancet Neurol. 2022;21:125–39.
⁴ QUVIVIQ^TM Summary of Product Characteristics. 2022. Available at: https://products.mhra.gov.uk. 
⁵ Data on file, Idorsia UK Ltd.
⁶ The International Classification of Sleep Disorders (3rd ed.; ICSD-3; American Academy of Sleep Medicine, 2014).
⁷ The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5; American Psychiatric Association, 2013).
⁸ Morin, CM, et al. Nat Rev Dis Primers. 2015;1:15026.
⁹ Hafner M., et al. The Societal and Economic Burden of Insomnia in Adults: An International Study. Santa Monica, CA: RAND Corporation, 2023.
¹⁰ Erickson, E.A., et al. MSMR. 2017;24(12):2-11.
¹¹ Chen, T-Y., et al. Sleep. 2017;40(11): zsx142.
¹² Shahly, V., et al. Arch Gen Psychiatry. 2012;69(10):1054-63.
¹³ Schwartz, J, et al. Curr Neuropharmacol. 2008;6(4):367–378
¹⁴ Muehlan, C, et al. J Psychopharmacol. 2020;34(3):326-335.
¹⁵ Everitt H, et al. Br J Gen Pract. 2014;64(619):e112-e119.
¹⁶ Kunz, D., et al. CNS Drugs. 2023;37(1):93-106.
¹⁷ Buysse, DJ, et al. Drug Discov Today Dis Models. 2011;8(4):129-137.
¹⁸ Levenson, JC, et al. Chest. 2015;147(4):1179-1192.
¹⁹ Wardle-Pinkston, S, et al. Sleep Med Rev. 2019;48.
²⁰ Muehlan, C, et al. Expert Opin. Drug Metab. Toxicol. 2020;16(11):1063–1078.
²¹ Boof, ML, et al. Eur J Clin Pharmacol. 2019;75(2):195-205.
²² Saper, CB, et al. Trends Neurosci. 2001;24(12).726-31.
²³ Gotter, AL, et al. BMC Neuroscience. 2013;14(1):14-19.

About Idorsia

Idorsia UK, an affiliate of 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.

With commercial operations based in London, we are helping to realise the company's ambition of bringing innovative medicines from bench to bedside.

Our goal is to build a commercial footprint that will deliver Idorsia's deep pipeline of products from its R&D engine to the UK market – with the potential to change the lives of many patients.

Headquartered in Switzerland, Idorsia Ltd was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 1,200 highly qualified specialists dedicated to realising our ambitious targets.

The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company 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.

SOURCE:- PR Newswire