New Insomnia Drug 'Dayvigo': What Makes It Different?

Existing sleep aids, such as benzodiazepines or zolpidem, forcibly suppress the brain, inducing sleep as if under anesthesia. According to Professor Won-Chul Shin, this method strongly suppresses the brain to achieve deep sleep.

However, this process suppresses slow-wave sleep (deep sleep), which is essential for physical recovery, and REM sleep, which aids emotional cleansing and memory storage, thereby distorting the normal sleep structure.

Taking existing sleep aids, especially zolpidem, can lead to temporary amnesia where the brain is awake but the drug's effects suppress brain function, preventing memory storage. Professor Won-Chul Shin illustrated this risk with a case of a patient who had a meal and attended a lecture at a hotel after taking zolpidem but remembered nothing.

In essence, the brain cannot function normally, preventing new information from being stored.

Walking in a groggy state while the effects of existing sleep aids linger increases the risk of falls and fractures. Professor Won-Chul Shin pointed out that among the elderly, who frequently wake up at night to urinate, accidents involving falls while under the influence of medication often occur, leading to fractures.

Furthermore, caution is needed when combining existing sleep aids with alcohol, as it can increase the risk of death due to respiratory depression.

Existing sleep aids develop tolerance with continued use, meaning their effectiveness diminishes. This is primarily due to increased liver metabolic efficiency, which accelerates drug processing, leading to an increase in dosage to achieve the same effect. Professor Won-Chul Shin explained this as a form of tolerance.

Concurrently, the weakening of GABA receptor activity in the brain can lead to a state of dependence, where one cannot sleep without the medication.

Such tolerance and dependence can cause severe withdrawal symptoms or rebound insomnia if the drug is discontinued after long-term use.

Professor Won-Chul Shin explained that intermittent use of sleep aids, like painkillers, only when needed, carries a low risk of dependence. That is, using them only once or twice a week when necessary, rather than daily, is relatively safe.

However, he emphasized that the act of enduring sleeplessness due to anxiety about not being able to sleep without the drug, and eventually seeking the drug, should be considered as already having entered a state of drug dependence.

After taking zolpidem, 'sleep-related eating disorder,' a type of parasomnia, can occur. This phenomenon involves actions such as retrieving food from the refrigerator without conscious awareness while asleep, with no memory of it the next morning.

Professor Won-Chul Shin pointed out that these side effects are a potential risk caused by the suppression of frontal lobe function.

Professor Won-Chul Shin explained that the brains of insomnia patients are in a state where normal inhibition is lost. While the frontal lobe should inhibit the hippocampus and limbic system, in insomnia patients, this inhibitory function is weakened, leading to persistent excitement in the limbic system. This increases anxiety and keeps the brain awake, which is one of the main causes of insomnia.

Excitation of the limbic system can also cause errors in appetite control, leading to abnormal behaviors such as rummaging through the refrigerator during sleep.

The loss of brain inhibitory function is associated with various abnormal behaviors during sleep, suggesting that this is a neurological issue beyond simply not being able to sleep.

While insomnia was previously attributed to a deficiency of GABA, a neurotransmitter that suppresses the brain, recent research has focused on the state of brain hyperarousal, or 'brain overactivity.' Professor Won-Chul Shin suggested that 'orexin overactivity' might be the core cause of this brain hyperarousal.

In normal individuals, the secretion of the arousal substance orexin is blocked at night, allowing for sleep, but insomnia patients have been found to maintain high orexin levels even at night.

This suggests that the paradigm for insomnia treatment should shift from brain suppression to regulating arousal substances.

Newly emerging sleep aids are called 'Dual Orexin Receptor Antagonists,' or 'DORAs' for short, as they block orexin receptors. While traditional sedatives worked by enhancing GABA activity to forcibly suppress the brain, DORAs directly block orexin, which acts as the arousal switch.

This mechanism is expected to reduce tolerance and dependence and induce a normal sleep structure, thereby improving the side effects of existing sleep aids.

Three orexin receptor antagonists have already been launched or are slated for launch globally, and they are soon to be introduced in Korea. The first is suvorexant (Belsomra), launched in 2014, currently used restrictively due to efficacy and side effect issues.

The second is lemborexant (Dayvigo), developed by Eisai in Japan, which is scheduled for launch in Korea in November this year. Finally, daridorexant (Quviviq) from Idorsia in Switzerland is expected to be launched domestically in the first half of next year.

The introduction of these three drugs in Korea is expected to provide new options for insomnia treatment.

Professor Won-Chul Shin stated that the clinical study results (SUNRISE 1) for the new insomnia drug 'Dayvigo' confirmed excellent efficacy. In a one-month clinical study, the drug group showed a reduction of approximately 20 minutes in sleep latency and a 43-minute decrease in time spent awake during the night. These results were objectively confirmed through polysomnography.

Notably, the drug's efficacy remained consistent during 12 months of long-term use, with no development of tolerance. Furthermore, no withdrawal symptoms or rebound insomnia occurred upon drug discontinuation, significantly improving upon the drawbacks of existing sleep aids.

Dayvigo demonstrated a significant sleep improvement effect compared to the placebo group, meaning it can provide a more stable treatment option for insomnia patients.

Existing sleep aids like zolpidem carried the risk of worsening sleep apnea due to their muscle relaxant effects. Professor Won-Chul Shin explained that phenomena such as intensified snoring and worsening apnea, similar to when consuming alcohol, could occur.

However, the new drug Dayvigo has been confirmed to have a lower risk of such issues, making it suitable for patients with sleep apnea. Clinical study results showed no decrease in oxygen saturation with Dayvigo use, proving its safety.

In the US, the new insomnia drug Dayvigo is classified as a 'Schedule 4' drug. This is a psychotropic medication, and there have been discussions about dependence because some patients experience inability to sleep when the drug is discontinued. However, Professor Won-Chul Shin interpreted this as potential proof of the drug's strong efficacy.

Currently, the pharmaceutical company is submitting data to relax the classification to 'Schedule 5,' and it is anticipated that it may be declassified from psychotropic medication status by the end of this year or next.

Relaxing the 'Schedule 5' classification is expected to reduce regulations on drug prescription and distribution, improving patient access.

Korea's low drug pricing policy is a major obstacle to the introduction of new foreign drugs. Professor Won-Chul Shin pointed out that under the current system, where high drug prices are only recognized if a drug significantly outperforms existing medications, it is difficult to set the price of a new drug at several thousand to over ten thousand won compared to low-cost drugs like zolpidem (150 won).

Additionally, Korea's drug prices are used as an international reference, creating a disadvantage in drug price negotiations with other countries. This frequently leads to multinational pharmaceutical companies 'Korea passing' the market, delaying new drug launches.

As a result, domestic patients have limited access to innovative new drugs already available overseas.

Ironically, even domestic new drugs that have achieved success in overseas markets face difficulties in domestic introduction due to Korea's drug pricing policies. Professor Won-Chul Shin cited SK Biopharm's epilepsy treatment 'Cenobamate' as an example.

Cenobamate is highly effective and recognized as the number one treatment in the US, but due to domestic drug pricing issues, it has not yet been officially launched in the Korean market.

This clearly demonstrates the institutional limitations in Korea, where drug price appropriateness assessment takes precedence over patient benefits.

The new insomnia drug 'Dayvigo' will be released as a non-reimbursed drug in Korea after failing to receive coverage. Consequently, it is priced at 1,631 won per pill, and the monthly cost, including pharmacy dispensing fees, is expected to be over 40,000 to 50,000 won.

Since patients must bear the full cost of non-reimbursed drugs without public support, the high cost can impose a significant financial burden on them.

Professor Won-Chul Shin expressed concern that these cost issues might make it difficult for patients who truly need the new drug to access it.