Lemborexant (DAYVIGO) – new sleeping pill reviewed

Lemborexant (brand name: DAYVIGO™), developed by Eisai, a Japanese pharmaceutical company, was recently approved in the US for the treatment of insomnia with symptoms of difficulty in falling asleep or maintaining sleep during the night. Although there is a number of prescription medications used in the UK for the management of insomnia, Lemborexant’s mechanism of action differs from drugs currently available in the UK. Will Lemborexant be available in the UK? How does it work? Is lemborexant effective? Can you be dependent on Lemborexant? These are some of the questions I will answer in this post.

Lemborexant: legal status

In the US, Lemborexant (DAYVIGO™) is classified as a controlled substance. This is not a surprise. In the UK, all drugs used in the management of insomnia are classified as controlled drugs of either Schedule 3 or Schedule 4. If Lemborexant is approved in Europe and consequently in the UK, one would expect Lemborexant to be a prescription-only medication classified as a controlled drug that falls into the Schedule 3 or Schedule 4 category.

Lemborexant: mechanism of action

Lemborexant is a dual orexin receptor antagonist.

A dual orexin receptor antagonist? What does it mean?

In plain English, Lemborexant stops orexins (chemicals) to work in the brain. Orexins play a role in sleep and wake cycles, and it is known for example that ‘faults’ in the orexin system lead to narcolepsy (Jacobson et al, 2016), a condition characterised by excessive and sudden patterns of sleep and excessive daytime sleepiness. Targeting this system in order to manage insomnia became a novel drug therapy option.

Lemborexant in the UK?

The announcement of Lemborexant about the approval in the US was released at the end of December 2019. It is expected for Lemborexant to be available for patients in the US at the end of March 2020. At the current time, it is not known if Lemborexant will be available in the UK in the near future.

Lemborexant is not the first drug classified as an orexin receptor antagonist. Approved in 2014 (US), Suvorexant (brand name: Belsomra), works in the same way as Lemborexant. Suvorexant is not available in the UK despite its treatment approval in the US five years ago.

Lemborexant (Dayvigo) form and dosage

Lemborexant (Dayvigo) comes in the form of a tablet. Two strengths of tablets are available:

• Lemborexant 5mg tablet
• Lemborexant 10mg tablet

The recommended (USclicense) dose is one 5mg tablet to be taken immediately before going to bed. The dose can be increased to 10mg, depending on the response. A dose of Dayvigo should be taken at least 7 hours before the planned time of awakening (FDA, 2019).

Lemborexant (Dayvigo): side effects

The most common side effect associated with the use of Lemborexant (Dayvigo) is somnolence (lethargy, fatigue). Other side effects reported include headaches, influenza (long-term study), and experience of nightmares or abnormal dreams.

Does Lemborexant cause dependence?

Many drugs currently used in the UK in the treatment of insomnia cause physical dependence and tolerance (reduce effectiveness over time). Data available from clinical trials and animal studies suggest that Lemborexant does not cause dependence and associated withdrawal symptoms after sudden discontinuation of the treatment or significant dose reduction (FDA, 2019).

Furthermore, clinical trial data also suggests that Lemborexant is not associated with rebound insomnia after stopping the treatment (ibid).

Lemborexant (Dayvigo): effectiveness

Sunrise 1 clinical trial: a short-term study on Lemborexant effectiveness and safety

The effectiveness of Lemborexant (Dayvigo) comes from a rather small clinical trial (Sunrise 1) of 1006 patients aged 55 years and over. Patients who suffered from insomnia were randomly allocated treatment with Lemborexant 5mg, Lemborexant 10mg, Zolpidem (a drug available in the UK for treatment of insomnia), or a placebo, a dummy pill, and took it for a month. Main outcomes of the clinical trial:

• Treatment with Lemborexant was associated with greater improvements in sleep onset (the time it takes to fall asleep) as compared with both placebo and zolpidem drug
• There was no difference between Lemborexant and Zolpidem in terms of how much people stayed awake after they initially fell asleep
  • • • Almost all individuals who used Lemborexant fell asleep in less than 20 minutes
• Patients on Lemborexant gained an additional 60 minutes of sleep per night as compared to the duration of sleep before the trial
• Treatment with Lemborexant was well tolerated and effective, especially when analysing sleep patterns in the late part of the night
• The effectiveness of the treatment with Lemborexant was seen at the beginning as well as at the end of the trial (first two and last two nights)
• At the end of the study, there was no evidence of withdrawal symptoms or rebound insomnia (patients having difficulties with insomnia again)
• Limitations of the study: patients age (only over 55s) and duration of the study (1 month)

Sunrise 2 clinical trial: long term study on Lemborexant effectiveness and safety

This clinical trial was conducted over 12 months period and involved 900 participants who either took Lemborexant 5mg or 10mg or a placebo pill. All patients suffered from insomnia disorder. This study was opened to patients aged 18 and over. This study confirmed:

• Lemborexant is well tolerated and effective when used long term (12 months treatment)
• Sleep onset was reduced by patients treated with Lemborexant 5mg and 10mg tablets
• Improved sleep maintenance

How much does lemborexant (Dayvigo) cost? 

In the US, lemborexant (Dayvigo) cost just over $300 per box of 30 tablets (GoodRx, 2022).

Insomnia management: what are the options in the UK?

Over the counter management of insomnia  

Hypnotics and anxiolytics are the mainstream of insomnia management in the UK. Temporary sleep problems can be managed with drugs available without a prescription from a pharmacy. Sedative antihistamines currently available as an aid to the relief of temporary sleep disturbance include:

• diphenhydramine hydrochloride tablets with many generic / supermarket own products available or branded products such as Nytol or Nytol liquid. 
• promethazine hydrochloride with popular brands, including Phenergan, and Sominex. Read more about promethazine and promethazine alternative drugs for sleeping. 

Related post: Sominxe vs Nytol for sleeping. 

Both antihistamines are common ingredients in cold and flu products and cough syrups.

Prescription-only medication in the management of insomnia

Hypnotics are the main class of prescription drugs used in the UK for the treatment of insomnia. Zopiclone is the most prescribed sleeping pill in the UK The main prescription drugs used include:

• Short-acting benzodiazepines — temazepam, loprazolam, lormetazepam. Temazepam has been out of stock long-term in 2022. 
• Non-benzodiazepines (the ‘z-drugs‘) — Zopiclone, Zolpidem, and Zaleplon (all are short-acting).

Read more about zopiclone and zopiclone alternative drugs. 

Conclusion

With a ‘novel’ mechanism of action, Lemborexant offers a new approach to the management of insomnia. Short-term and long-term clinical trials show benefits in treatment with good drug tolerability; however, both studies represent a small sample size (number of people participating in clinical trials). 

Will Lemborexant be available in the UK?

At this time, it is not known if Dayvigo will be available in the UK. However, looking at available clinical trial information, this would bring a ‘novel’ therapy option for people who suffer from insomnia. The question of availability is also related to affordability by NHS.

If Lemborexant is approved in the UK and Europe, we are left with the uncertainty of the price of the drug (currently not known) and NICE recommendations on its use in relation to cost-effectiveness. With the current price of around $300 per box of 30 tablets it is very unlikely for NICE to approve this medication for the treatment of insomnia in the UK. 

References:

GoodRx (2022). Dayvigo. Available at: https://www.goodrx.com/dayvigo Accessed on 15/12/2022