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 the 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, and how does it compare to commonly used Zolpidem in the treatment of insomnia? 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 into the European market and consequently in the UK, one would expect it to be a prescription-only medication classified as a controlled drug that falls into 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 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?
Lemborexant approval in the US was announced 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. Suvorexant is 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:
- 5mg tablet
- 10mg tablet
The recommended (US licensed) 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: 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 (drug available in the UK for treatment of insomnia) or 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
- Patient treated with Dayvigo 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 pattern in the late part of the night
- 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 5mg or 10mg tablet or a placebo pill. All patients suffered from insomnia disorder. This study was opened to patients aged 18 and over. This study confirmed:
- The drug is well tolerated and effective when used long term (12 months treatment)
- Sleep onset was reduced by patients treated with both 5mg and 10mg tablets
- Improved sleep maintenance
Insomnia management: what are the options?
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 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 (read more about Nytol liquid in my separate post)
- promethazine hydrochloride with popular brands, including Phenergan, Sominex.
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.
- Non-benzodiazepines (the ‘z-drugs‘) — Zopiclone, Zolpidem, and Zaleplon (all are short-acting).
You can read more about prescription sleeping drugs (recommendations and popularity) in a separate post.
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). The occurrence of uncommon side effects is defined between 1 in 1000 and 1 in 100 patients and rare between 1 in 10000 and < 1/1000. Both studies did not necessary provided a sufficient number of patients to show all possible side effects.
Will Dayvigo be available in the UK?
At this time, it is not known if Dayvigo will be available in the UK. Introduction to the UK market would offer a good alternative and ‘novel’ therapy option for people who suffer from insomnia. The question of availability also related to affordability. 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. One thing we know for sure: newly approved drugs do not come cheap.
- Eisai (2019). U.S. FDA Approves Eisai’s DAYVIGO™ (lemborexant) for the Treatment of Insomnia in Adult Patients. Available at: http://eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients Accessed on 08/01/2020
- FDA (2019). HIGHLIGHTS OF PRESCRIBING INFORMATION. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212028s000lbl.pdf Accessed on 07/01/2020
- Jacobson L.H., Chen S., Mir S., Hoyer D. (2016) Orexin OX2 Receptor Antagonists as Sleep Aids. In: Lawrence A., de Lecea L. (eds) Behavioral Neuroscience of Orexin/Hypocretin. Current Topics in Behavioral Neurosciences, vol 33. Springer, Cham Available at: https://doi.org/10.1007/7854_2016_47 Accessed on 07/01/2020