Why did the U.S. FDA approve this new drug amidst opposition?
Author: Ju Chuanyangzi
The U.S. FDA (Food and Drug Administration) officially approved the use of Aducanumab (Aducanumab) on June 7. This drug will be marketed under the brand Aduhelm. It is the first Alpha drug approved by the FDA since 2003. The new drug for the treatment of Zheimer’s disease is also known as the first drug that can prevent or delay the progression of the disease and “slow down” the cognitive decline of patients.
This is a great thing, because it has brought good news and hope to many Alzheimer’s patients, but it has triggered more intense debates on the efficacy and side effects of the drug in the US medical community, and even led to three FDA experts. And resign.
The US FDA specifically stated that the approval of this new drug is through a so-called “accelerated approval pathway” (accelerated approval process), and has imposed stringent additional conditions on its manufacturer Biogen, requiring the company to Restart a new clinical trial cycle, which is called the fourth clinical trial cycle or post-approval clinical trial cycle. If the trial result of this cycle fails, the FDA can revoke the approval of the drug and order it to be delisted.
The opposing party’s reason is that in the completed clinical trials of Bojian Company, sufficient evidence has not been collected to prove the therapeutic effect of the drug, and it may also cause side effects such as cerebral hemorrhage. If the FDA approves the drug on the market, it will be given to it. Endorsement makes it costly US$56,000 per year for patients who are already suffering from the disease to fail to get the expected curative effect. This will not only cause direct economic losses to the patient, but its side effects may also cause other health damages. The third expert to resign from the FDA is a professor at Harvard Medical School, who called “this is the worst decision to approve a drug in U.S. history.”
Alzheimer’s disease treatment drugs undoubtedly have great commercial value. World-renowned large pharmaceutical companies have invested in the fierce competition in the research and development of such drugs, but so far have invested tens of millions of dollars in research and development expenses and developed hundreds of new drugs. All failed. Adukanumumab is also a dystocia who has been declared failed several times and has experienced many setbacks. On the day it was approved by the FDA, Bojian’s stock price soared by 64%, which proved the market’s expectations for the drug welcome.
The FDA had a precedent for the failure of Alzheimer’s treatment drugs. Tacrine was approved by the FDA, but it has been discontinued because of its toxicity and was removed from the FDA’s official website. Therefore, we still have to carefully look at the scientific evidence and wait for the results of the fourth phase of the adukanumumab clinical trial.
Causes of Alzheimer’s disease
There are many causes of dementia, mainly caused by damage to brain cells, followed by cerebrovascular disease, brain damage due to mechanical head trauma, or due to lack of brain cell nutrients. The Japanese medical community believes that metabolic diseases, autoimmune diseases, respiratory, liver, and kidney diseases may also be the causes of senile dementia. In addition, people with diabetes and people with high blood pressure, high blood lipids, and high cholesterol are at high risk of developing dementia. This shows that it is not only the elderly who suffer from dementia. There are currently about 37,500 “young dementia patients” under 65 years old in Japan, and it is predicted that the number of young patients will increase year by year.
Alzheimer’s disease is the most common type of dementia in the elderly, and its pathology has not been fully explained. At present, the beta amyloid hypothesis is dominant, which is believed to cause dementia in the process of brain nerve degeneration and partial brain atrophy.
Based on this hypothesis, it is believed that if a safe drug that blocks the accumulation of beta amyloid is developed, Alzheimer’s disease will not cause further neuropathy. If this happens, the progression of dementia may be completely prevented. In this sense, early detection and early treatment intervention will become more important in the future. Therefore, most of the research and development of new drugs focuses on treating symptoms before they appear, with the purpose of preventing or delaying the onset and progression rate of Alzheimer’s disease. Adukanumab is a drug based on this hypothesis and theory.
What is used to treat patients with middle and late stages of dementia? Modern medicine believes that brain cells and nerve cells that have degenerated and disappeared will not regenerate, and the lost functions are difficult to recover, and dementia is irreversible. So far, humans have not developed a drug that can “cure” the disease.
At present, Japan mainly uses a combination of drugs and non-drug treatments, and the expected effect is only to reduce symptoms and delay the deterioration of the disease as much as possible. The drugs mainly use 5 kinds approved by the US FDA. Non-drug treatment methods are mainly physical therapy and some puzzle activities, including arithmetic, handicraft making, gymnastics, group games, etc.
Why did the FDA approve this new drug amidst opposition?
According to statistics released by the US FDA, there are currently about 6.2 million elderly patients with dementia in the United States, of which 5.8 million are Alzheimer’s patients. It is expected that the number of elderly patients with dementia in the United States will double to 16 million by 2050. The number of patients with Alzheimer’s disease is also increasing rapidly. The patients are mainly elderly people over 65 years old, of which 80% are elderly people over 75 years old, and 2/3 are female patients. The World Health Organization (WHO) said that there are about 50 million elderly patients with dementia in the world, and it is increasing at a rate of 10 million patients every year, of which nearly 70% are patients with Alzheimer’s disease.
China is the country with the largest number of Alzheimer’s patients in the world, accounting for a quarter of the total number of patients in the world. As of 2019, China has more than 10 million patients, and it is expected to exceed 40 million by 2050.
Looking at the situation in Japan, the average life expectancy of the Japanese is the longest, and the longest life span of healthy living is also the longest. However, because the number of elderly people is increasing year by year, the prevalence of dementia in Japan is ranked first in the world. According to the Organisation for Economic Cooperation and Development (OECD), Alzheimer’s disease patients in Japan accounted for approximately 2.3% of the total population in 2017, and may reach 3.8% in 2037. According to the Ministry of Health, Labour and Welfare of Japan, there will be about 6 million elderly dementia patients over 65 in Japan in 2020, and it is expected to reach 7 million by 2025, accounting for 20% of the total elderly population. The beds in Japanese hospitals are mostly occupied by elderly patients who require long-term care. The medical expenses paid to elderly long-term inpatients account for 11% of the total hospital expenses, which is much higher than the average 4% of OECD member countries. Japan’s annual health expenditure has accounted for 10.7% of the country’s GDP.
Alzheimer’s disease was discovered by German psychiatrists in 1906, but until 115 years later, neither Japan nor the United States, with advanced medical technology, has a drug that can cure Alzheimer’s disease. There are currently five FDA-approved drugs in use in the United States, all of which can only relieve symptoms or delay the evolution of the disease, and are used in the early stages of the disease.
The severity of dementia in the elderly has been placed at the height of a “national strategic issue” by various countries
In 1994, the International Alzheimer’s Association (ADI) and the WHO set September 21 as World Alzheimer’s Day (World Alzheimer’s Day), calling on the world to pay attention to Alzheimer’s disease. The WHO pointed out that senile dementia is one of the most important diseases that endanger the health of the elderly and cause the increase of the elderly disabled population. It is also the most important disease that causes the death of female elderly people, which is higher than the death rate caused by heart disease and stroke. The physical, psychological, social, and economic impacts caused by it are enormous, not only for the patients themselves and their families, but also for countries and the whole society.
Accompanying the aging of the population is the rapid increase of elderly dementia patients. The United Kingdom is aware of the seriousness of this problem. As early as 2009, the United Kingdom set up a national dementia care strategy for the elderly and held the “Elderly Dementia Symptoms Summit” was attended by 8 countries. Japan also formulated the first national dementia strategy for the elderly in 2013, which was called the “Orange Plan” (2013~2017). In 2015, the “New Orange Project” called for the increase of professional and non-professional elderly dementia care workers across the country to support and help elderly dementia patients and their families across the country, so that they can more easily obtain treatment and care in the nearest community service.
In 2012, the United States Department of Health and Human Services (HHS) formulated the “National Alzheimer’s Disease Project Act” (NAPA), which set five goals: to be able to prevent and effectively treat Alzheimer’s disease by 2025; the best Improve the quality and efficiency of care; increase support for Alzheimer’s patients and their families; strengthen public awareness and participation; track progress and promote improvement.
Obviously, judging from the efficacy of drugs currently on the market and the speed of new drug development, the first goal of NAPA in the United States is estimated to be difficult to achieve. It is only 4 years from 2025, and there are only 5 drugs that can be used, and the development of new drugs is extremely slow. .
(The author is an expert in the Japanese pension industry and the president of Yoko Enterprise Management Consulting Company)
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