The new generation of anti-insomnia drugs is coming, with a market value of billions, and SIMCERE PHARMA takes the lead

Baldness, round waist, fatigue, and insomnia are the three main characteristics of contemporary working individuals. The first two have become hot topics in both real life and the capital market, with baldness treatments, hair transplants, weight loss drugs sparking rounds of speculation, while insomnia medications have been lukewarm. The reason behind this is the lack of progress in the development of new insomnia drugs, and traditional insomnia medications not only harm the body but also lead to dependency.

Recently, there is good news in the field of insomnia medication. The National Medical Products Administration announced that SIMCERE PHARMA (02096)'s Desmopressin Hydrochloride Tablets (referred to as "Desmopressin" below), marketed as Keweike, has had its new drug application accepted by the Chinese Medical Products Administration. According to the Wise News Finance APP, Desmopressin is a new generation anti-insomnia drug developed through collaboration between SIMCERE PHARMA and Swiss company Idorsia. It is a dual orexin receptor antagonist (DORA) and has been approved for marketing in countries such as the United States, the United Kingdom, Italy, Germany, Switzerland, and Canada. With its outstanding safety and non-addictiveness, Desmopressin is currently the only DORA-class insomnia treatment approved by the European Medicines Agency to improve daytime function.

The launch of Desmopressin signifies that the fourth generation of anti-insomnia drugs, represented by orexin receptor antagonists, is gradually taking the stage. This provides a new treatment option for numerous insomnia patients in China and adds a heavyweight product to SIMCERE PHARMA's central nervous system portfolio. This further strengthens the company's leading position in the central nervous system field, forming a positive outlook for SIMCERE PHARMA.

Traditional Anti-Insomnia Drugs Set to be Overturned

Unlike traditional sedative-hypnotic drugs that promote sleep by sedating the brain, Desmopressin helps patients fall asleep and stay asleep by blocking the binding of orexin neuropeptides (orexin A and orexin B) to their receptors, without causing a hangover or drowsiness the next day. Overseas Phase III clinical data published in "The Lancet Neurology" validates the effectiveness and safety of Desmopressin in the Chinese population of insomnia patients, offering a new choice for insomnia treatment.

In terms of efficacy, during the first and third months of treatment, Desmopressin significantly reduced patients' time to fall asleep, nighttime awakenings, and increased total self-reported sleep time compared to the placebo. With a half-life of approximately 8 hours, Desmopressin can meet nighttime sleep needs without causing residual effects the next day, meeting the current clinical demand for insomnia medications.

In terms of safety, Desmopressin has good safety and tolerability, with no evidence of rebound insomnia, withdrawal symptoms, or drug abuse found. Clinical data from 12 months of continuous treatment support the long-term use of Desmopressin.

Insomnia is one of the most common sleep problems, with main symptoms including difficulty falling asleep (adults with a sleep onset latency exceeding 30 minutes), sleep maintenance disorders (awakening ≥2 times per night), early awakening, decreased sleep quality, and reduced total sleep time (usually less than 6.5 hours). Symptoms must occur at least three times a week and must be accompanied by daytime functional impairment or distress.

Currently, internationally recognized medications for treating insomnia include benzodiazepines, non-benzodiazepine drugs, melatonin and melatonin receptor agonists, orexin receptor antagonists, and antidepressants with hypnotic effects Benzodiazepines and non-benzodiazepine drugs are currently the most common sedatives on the market. Benzodiazepine receptor agonists (BzRAs) act on the α receptors of GABAergic neurons to broadly sedate the brain. However, these drugs often lead to symptoms such as dizziness, drowsiness, fatigue, and cognitive impairment in patients, and pose various safety issues. In addition, benzodiazepines are known to disrupt sleep structure, with significant residual effects the next day, often leaving patients feeling fatigued upon waking.

Compared to traditional sleep aids, orexin is a peptide that promotes wakefulness through receptors OX1R and OX2R. The orexin system stimulates target neurons in the arousal system, leading to the release of several chemicals that promote wakefulness (dopamine, serotonin, histamine, acetylcholine, norepinephrine). Normally, orexin levels rise during the day as wakefulness increases, then decrease at night. Overactivity in the arousal system is a key factor in insomnia.

Orexin receptor antagonists work by blocking two orexin receptors to inhibit the overactive arousal pathways in insomnia patients, thereby promoting sleep with strong targeting. Compared to traditional sleep medications, orexin receptor antagonists can reduce arousal drive, induce sleep without altering sleep structure, have no residual effects the next day or drug dependency, and are poised to be a disruptive iteration of traditional sleep aids.

A Hundred Billion Anti-Insomnia Market, SIMCERE PHARMA Leads by a Wide Margin

Currently, there are three orexin antagonists on the global market, with none available domestically. Lemborexant from Eisai and Dallirexant introduced by SIMCERE PHARMA have submitted listing applications domestically, while Fazamorexant from Yangtze River is in Phase III clinical trials.

Suvorexant, a Merck product, is an orexin receptor antagonist and the world's first orexin receptor antagonist to be approved for marketing, receiving FDA approval in 2014. Despite being the first to market, Suvorexant's sales have not been ideal, with global sales of $318 million in 2021, dropping to $258 million in 2022. The less-than-ideal sales may be related to market pricing and its long half-life. Data shows that Suvorexant's daily treatment cost in the US is $15, while the commonly used sleep aid Zopiclone costs $0.99 per day, indicating a significant price difference. Furthermore, Suvorexant has a half-life of 12-15 hours, leading to daytime drowsiness after administration, affecting daily life and work.

It is worth noting that although Suvorexant has not yet been approved for marketing domestically, it was already included in the second category of psychotropic drugs in April 2023, which will have a certain impact on its sales upon its future domestic market launch Leborayson, developed by Weicai, was approved by the FDA in December 2019 for the treatment of adult insomnia with difficulty initiating or maintaining sleep. After its launch, Leborayson's sales continued to rise, reaching a global sales of $240 million in 2022. In January 2024, Leborayson applied for listing in China, accepted by the CDE, for the treatment of adult insomnia, especially difficulty initiating or maintaining sleep. It is worth mentioning that Leborayson has a half-life of 17-19 hours, which may also affect daily life and work.

Compared to the former two, Dalileison has a shorter peak period, with a half-life of only 8 hours. Clinical trials have shown that Dalileison has good pharmacokinetic characteristics, with about 80% of the drug being cleared from the body after a night's sleep, minimizing residual effects. Therefore, Dalileison may have a wider audience.

In addition, domestically, Fazamorexant from Yangtze River has made rapid clinical progress and is currently in Phase III. It is evident that the competition landscape for dual orexin receptor antagonists in China is favorable.

In terms of market space, according to the Datamonitor database, there were approximately 1.4 billion insomnia patients globally in 2019, with 690 million in Asia. Furthermore, according to the "China Healthy Sleep Survey Report (2023)", nearly three-quarters of people have experienced insomnia, with over 300 million Chinese suffering from sleep disorders. Among them, difficulty falling asleep leading to insomnia is the top issue. Additionally, according to the "China Sleep Research Report 2024", the sleep index of Chinese residents in 2023 was 62.61, a decrease of 5.16 from 2022 and 2.17 from 2021, marking a new low in the sleep index over the past three years, indicating a deteriorating sleep condition among residents, which is quite serious.

The vast insomnia population creates a huge pharmaceutical space. According to statistics from the Pharmaceutical Economics Report, in 2021, the sales of hypnotics/sedatives in sample hospitals in China reached nearly 2 billion RMB, with a drug purchase amount of 5 billion RMB in public hospitals nationwide. Huajing Industry Research Institute predicts that the global insomnia treatment market is expected to grow from $3.4 billion in 2023 to $43.7 billion in 2028; the overall market size of China's sleep economy is expected to exceed 1 trillion RMB by 2030. The market size of insomnia drugs in China increased from 9.84 billion RMB in 2016 to 11.7 billion RMB in 2020, and is expected to reach nearly 13 billion RMB by 2022.

Currently, traditional anti-insomnia drugs dominate the domestic market. The launch of orexin receptor antagonists will fill the gap in the domestic market. After the launch of these products, they are expected to quickly capture the market space of traditional drugs, with Dalileison, which has shown more prominent clinical performance, poised to stand out Besides the impressive product performance data, SIMCERE PHARMA has a nationwide marketing network and leading commercialization capabilities. By 2024, SIMCERE PHARMA has a academic promotion team of over 4,000 people. It is not difficult to foresee that once Daleraysheng is approved for listing, with the help of SIMCERE PHARMA's existing sales channels, its market space will quickly open up, helping more insomnia patients get through sleepless nights.

Conclusion

From a capital perspective, the pharmaceutical industry is still in a capital winter phase, with overall valuations of pharmaceutical companies being very cheap. This is the perfect opportunity to explore good companies.

Taking SIMCERE PHARMA as an example, its jointly developed Daleraysheng NDA has been accepted by the NMPA, and currently there are no products approved for listing in the domestic appetite suppressant receptor antagonist market. Compared to competitors, Daleraysheng performs better in all aspects and is expected to become a benchmark in this segmented field. After approval for listing, it is expected to quickly gain market share, benefiting SIMCERE PHARMA as well.

It is worth mentioning that 2024 will also be the peak of commercialization for SIMCERE PHARMA. Xianbixinsublingual tablets were accepted by the NMPA in June 2023; Suvisita monoclonal antibody combined with platinum-based chemotherapy for recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has failed platinum-based chemotherapy was submitted for listing to the NMPA in March 2024 and accepted; ADC189 is expected to submit an NDA in 2024. With the commercialization of multiple innovative drugs, SIMCERE PHARMA's performance is also guaranteed.