As the Moon Jae-in administration speeds up the implementation of its policy called the “state responsibility for dementia,” the domestic pharmaceutical industry is aflutter with excitement.

The government has set about to build related healthcare system, opening regional dementia centers and beefing up workforce there as well as replenishing dementia wards at public healthcare centers throughout the country. Such an atmosphere also seems to have encouraged the domestic drugmakers.

The development of dementia treatment is one of the most difficult areas, failing even multinational pharmaceuticals that pour billions of dollars in research and development a year.

Many international pharmaceutical companies have invested trillions of dollars in Research and Development to create a cure for dementia, and they have failed. Stated reversely, however, it means that a groundbreaking therapy has not been developed yet; anyone succeeds in producing it will be able to monopolize the global market. The government’s policy support is adding to the motivation to develop the drug.

A difficult task even for multinational pharmaceuticals famous for R&D

Developing a therapy for Alzheimer’s disease is one of the areas receiving greatest attention throughout the world. The number of dementia patients is growing along with the increase in average life expectancy, but there has been no breakthrough treatments.

According to the World Health Organization (WHO), the global dementia population is expected to jump from 44 million in 2013 to 76 million in 2030. In South Korea, too, the number is estimated to increase to 2.71 million by 2050.

Social and economic costs of Alzheimer's disease are also increasing rapidly. According to Professor Lee Jeong of Yonsei University's College of Medicine, South Korea's socio-economic costs from dementia are estimated to increase to 18.9 trillion won ($16.6 billion) in 2020 and to 38.9 trillion won in 2030.

Although dementia patients are rapidly growing in number, dementia therapies of a newly developed mechanism are insufficient. Among the most frequent cases of dementia are the Alzheimer's disease and vascular dementia. Medications that are in markets or being developed are also concentrated on the Alzheimer’s. Leading causes of the disease are the reduction of acetylcholine, the deposition of beta amyloid, and over-oxidation of Tau, which are known to cause damage to nerve cells.

Among the existing therapies are Aricept (compound: Donepezil), Exelon (compound: Rivastigmine), Razagyne (compound: Galanthamine), and Namenda (compound: Memantine). These dementia medications, however, can only alleviate symptoms such as improving cognitive functions but cannot treat it fundamentally. That is why many pharmaceutical companies are anxious to develop a treatment.

The global pharmaceutical companies focus their attention on developing cures of the new mechanism but are finding it not easy to succeed. Multinationals such as Pfizer, Roche, Novartis, and Eli Lilly are pouring billions of dollars into the development of cures for dementia but have produced few noticeable outcomes.

Recently Eli Lilly has attracted the most attention with Solanezumab, a candidate substance for curing Alzheimer's disease but failed to produce satisfactory results in its phase 3 clinical trials. The phase 3 clinical tests, called “EXPEDITION 3,” conducted on patients with mild cases, failed to satisfy the primary evaluation variable of Alzheimer’s Disease Assessment Scale Cognitive (ADAS-cog). Eli Lilly has spent 11 trillion won for its development but declared its failure last year.

That didn’t cool the development fervor of other global pharmaceutical firms, including Merck, Roche, Eli Lilly, Biogen, Pfizer, AstraZeneca, Abbvie, Novartis, Sanofi, GlaxoSmithKline.

Domestic pharmaceutical companies, too, are making extensive investment

Domestic pharmaceutical companies are also investing heavily in developing treatments for Alzheimer's disease. They are trying to develop drugs by changing the dosage of the existing medicines or improving them as well as investing in developing therapies of new mechanisms.

Among major domestic pharmaceuticals developing candidate substances for dementia treatments are SK Chemical _SK케미칼 (SK PC B70M wonder drugs by using natural substance), Kwangdong Pharmaceutical _광동제약 (KD-501, wonder drugs by using natural material), PURIMED _퓨리메드(PM012, wonder drugs by using natural substance), DaeHwa Pharm_대화제약 (DHP 1401), MEDIPOST_{메디포스트} (Neurostem, a stem cell therapy), ILDONG Pharmaceutical일동신약 (ID1201, wonder drugs by using natural substance), Medifron_메디프론(RAGE antagonist), Jeil Pharmaceutical_제일약품 (Dehydroevodiamine/JGK-263), Dong-A Socio Holdings _{동아쏘시오 홀딩스}(DA 9803, wonder drugs by using natural substance), Boryung Pharmaceutical 보령제약(BNT002), CHA Biotech_{차바이오텍} (DB-AC-02), GemVax & KAEL _{젬벡스앤카엘}(GV1001), and Whanin Pharm_환인제약(INM176).

Note: This table is the compilation of the data at the stock market and the approvals of the companies’ clinical trial plans by the Ministry of Food and Drug Safety.

Not only businesses but academic and research institutions are going all out to develop dementia therapy by developing candidate substances, transferring related technologies and attracting investment in them. Unfortunately, however, there have been no significant outcomes.

Currently, Dong-A Socio Group is making heaviest investment in the development of treatment for dementia. In 2013, the company became the first Korean drugmaker to open a dementia research center under the initiative of the private sector. It did so to play the role of a hub for developing dementia treatments by putting together research organs and experts in one place.

Upon the establishment of the research center, it embarked on the development of a therapy and is currently developing two drugs – one of them inhibits the decline of the Brain-derived neurotrophic factor (BDNF), and the other is the inhibitor of the hyperphosphorylation of tau protein. The DA9803, based on natural substance, has the mechanism to inhibit the formation of beta-amyloid

Medifron drew attention in 2010 by exporting its RAGE antagonist to Roche at $290 million. In 2011, Medifron once again emerged as an active player in this sector by agreeing to develop the beta amyloid coagulant inhibitor. However, the candidate substance is reportedly still at a pre-clinical stage, and Medifron has yet to receive a down payment. Daewoong has also pulled out of the project to develop DWP09031 jointly with Medifron. Medifron is receiving renewed attention, however, as it won the approval for its Alzheimer’s diagnosis kit from the Ministry of Food and Drug Safety this past May.

DaeHwa Pharmaceutical’s DHP1401 gathered momentum for development as it was selected as one of the task projects of the Ministry of Health and Welfare last year. DaeHwa will collaborate with Konkuk University Medical Center (KUMC) until the December of 2018 to carry out phase 2 clinical trials to assess the efficacy and safety of the DHP 1401. In animal model studies, the candidate substance significantly curbed the formation of beta-amyloid, which is known to cause dementia, and confirmed it has effects on protecting nerve cells and restoring memory power.

Many other drugmakers are also pushing to develop dementia therapies. It will likely take a long time for the domestic pharmaceutical companies to commercialize dementia treatments, however, as most of their projects remain at the stage of pre-clinical or phase 1 or 2 clinical trials. Also, even candidate substances that have completed clinical trials have yet to undergo a commercializing process, which means there are virtually no materials that have been successfully developed as therapies true to their name.

Will the government’s support give new impetus to their efforts?

It is against this backdrop that the government has begun to provide support for the development of dementia treatments. First of all, the government is to disclose researches resources needed for the study of Alzheimer's disease. Korea Centers for Disease Control & Prevention (KCDC) and Korea National Research Institute of Health (KNIH) said they would make public their human body resources to be used for the research of the Alzheimer's disease and Parkinson's disease. To be unveiled are epidemiological information that contains 56 variables, including demographic characteristics, environmental factors and disease records, and human biological materials, such as unique genetic information by diseases, serum, plasma, and DNA. If such research sources are made public, they will likely give momentum to the research and development of dementia treatments.

Most important of all, however, is the government’s support for the development of dementia therapy on the national level, industry executives say in unison.

"The development of medicine for Alzheimer's disease is a difficult project even for the multinational pharmaceutical companies. The Korean pharmaceutical industry, which lags behind in the scale of R&D investment and workforce, will be able to develop successful treatments if the government gives full support,” said an industry executive. “As their development can't happen overnight, however, we are concerned that the government may want a quick result and stop its support if there are few short-term outcomes.”

He added that the industry hopes the government will “throw full support behind the industry’s efforts, as part of the Moon administration’s drive for ‘the state responsibility for dementia patients.’”

lhs@docdocdoc.co.kr

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