In 2021, the incidents of fathers saving children and mothers purchasing children's medicines on behalf of children were identified as "drug trafficking". Behind the black humor of the absurdity of the human world, there is the fact of regret:
Only 5% of rare diseases have drugs to treat, even if they become one of the 5%, some Chinese patients can only hope for drugs to sigh, because many drugs have not yet been listed in China, and some rare disease drugs are listed in China for 10 years later than abroad.
In order to survive, many rare disease patients can only choose to find medicine overseas, and many patients have been deceived, making the family economy worse.
If rare diseases are a genetic curse, policies that support drug development and marketing are the key to breaking the spell.
The dilemma for pharmaceutical companies
In 2012, when the first China Rare Disease Summit Forum was held, there were almost no domestic enterprises, and only Bayer, Jianzan and other companies participated in the meeting.
In the past 10 years, China's innovative drugs have emerged in an endless stream, why are there still so few drugs for rare diseases?
Worrying about R&D not getting its costs back is just one aspect. Han Jinxiang, president of the Shandong Academy of Medical Sciences and president of the Shandong Rare Disease Prevention and Control Association, generally believes that when the number of patients is 300,000 to 500,000, a drug is likely to make money. Although China does not yet have an official definition of rare diseases, the number of patients with many rare diseases in China is less than 100,000, or even less than 30,000, which means that the market for a single rare disease drug is too small.
The other is that even if pharmaceutical companies decide to deploy rare disease drugs in China, they are facing a series of problems.
The first is the long time for drugs to be approved. Before the launch of the drug review reform in 2015, it took 18 months for drugs to start declaring and listing to finally getting approval documents. The same rare disease drug, Australia this process is 5 days, the United States, South Korea is 1 month.
A research and development personnel who once worked for the US FDA told the Health Bureau that the US FDA has thousands of people in the approval, and the number of professionals in the domestic drug approval is too small, and the approval speed is slow. At the end of 2014, there were only 89 reviewers in the Drug Review Center who specialized in technical review.
The second is the difficulty and cost of research and development. Generally speaking, the development of new drugs follows the "double ten law", 10 years of research and development, spending 1 billion US dollars. At the 2021 China Biomedical Industry Innovation Conference, the Bureau learned that the cost of new drug development is rising year by year, reaching up to US$2.6 billion. Rare diseases Due to the small number of patients, clinical trial organization is very difficult, and the cost is higher.
Many companies have made a "smart" decision. R&D personnel of a rare disease company said that 80% of rare diseases are genetic diseases, and less than 20% are related to tumors. Most companies that develop "rare disease drugs" have chosen to target tumors.
Then there are concerns about market protection. A rare disease drug that has been successfully listed also faces the challenge of being imitated.
In fact, on the whole, the success rate of rare disease drug development exceeds that of other innovative drugs.
According to WuXi AppTec's research, from 2011 to 2020, the success rate of rare disease drugs for non-tumor indications in the United States to develop and approve reach an average of 17%, which is higher than the average development success rate of drugs of 7.9%. In the 4 phases of clinical development of rare disease drugs, the translational success rate is also higher than the industry average.
Rare diseases are mostly genetic diseases, and there is a clear treatment path, which can improve the success rate of development. In addition, after developing rare disease indications, pharmaceutical companies can also broaden the indications for drugs and expand the target market.
Some rare disease companies concluded to the media in 2017 that although the state has been encouraging the research and development of rare disease drugs, it is far from enough, and there is a lack of specific implementation rules.
Policy is shifting
The rare disease drugs on the market in China are mainly imported patented drugs and domestic generic drugs, and domestic original research is still in its infancy.
In 2017, the news of the state's plan to introduce the "First Rare Disease Catalogue" spread, and the market realized that there may be favorable policies for the approval of relevant drugs. Because the catalogue clearly defines which are rare diseases, the policy can provide targeted help and support.
At the 2021 China Rare Disease Conference, Xu Xiaoqiang, then director of the Chemical Drug Division of the Drug Registration Department of the State Food and Drug Administration, concluded that through the establishment of laws and regulations, the process of listing new drugs for rare diseases has been accelerated, which is one of the achievements of the Food and Drug Administration in recent years.
After the release of the "First Rare Disease Catalog", the State Food and Drug Administration mainly did three major pieces of work: one is to speed up the review and approval and reduce the time cost of enterprises; the second is to help enterprises develop clinically and reduce the research and development costs of enterprises; the third is to protect the data of rare disease drugs to ensure the return within a certain period of time after listing.
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In terms of speeding up approval, the Food and Drug Administration has exhausted various means. Under normal circumstances, the approval time for new drugs is 130 working days, and after the release of the First Rare Disease Catalogue, the FOOD and Drug Administration has compressed the approval time for rare disease drugs to less than 70 working days.
It's like changing directly from a green-skinned train to a high-speed train.
Compressing the approval time limit, Sanofi's experience is particularly obvious. After multiple sclerosis was included in the "First Rare Disease Catalogue", Sanofi's therapeutic drug "Obatier" was listed in just 58 days, setting a record for the fastest marketing of rare disease drugs in China that year.
At the same time, the FOOD and Drug Administration has also opened its doors to encourage excellent foreign rare disease drugs to come to China for listing.
After the introduction of the catalogue, the State Food and Drug Administration has successively released a list of 3 batches of new drugs urgently needed for clinical use, and among the 73 drugs, 34 are rare disease drugs, accounting for almost half, and can accept overseas data for direct approval.
In November 2020, the Food and Drug Administration said that rare disease drugs that are not listed in China can be conditionally approved for listing on the premise of meeting clinical needs.
Due to the small number of patients with rare diseases and the difficulty of carrying out randomized double-blind controlled trials, the State Food and Drug Administration began in August 2020 to allow appropriate reduction of clinical data through evidence of real-world clinical effects in China and reduce the difficulty of developing rare disease drugs.
On January 6, 2022, the Drug Evaluation Center of the State Food and Drug Administration issued the Technical Guidelines for Clinical Research and Development of Drugs for Rare Diseases. The principle suggests that clinical data on rare diseases can be obtained through natural history studies of diseases, public literature reports, patient registration platforms, clinical staff surveys, and patient surveys.
According to the data released by the National Medical Insurance Bureau, as of December 31, 2021, more than 60 rare disease drugs have been approved in China. Among them, according to the incomplete statistics of the Health Bureau, since the release of the First Rare Disease Catalogue, the State Food and Drug Administration has approved the listing of at least 27 rare disease drugs, covering 16 diseases in the catalogue. Coupled with the treatment of non-catalog rare disease drugs urgently needed in clinical practice such as "neurotrophic keratitis", in less than 3 years, the FOOD and Drug Administration has successively approved nearly 30 rare disease drugs for marketing.
The State Food and Drug Administration also responded positively to the concerns of pharmaceutical companies about imitation, and issued the Implementation Measures for the Protection of Data for Drug Trials (Interim) (Draft for Comments) in April 2018, saying that for drugs for rare diseases or special drugs for children, a 6-year data protection period will be granted from the date when the indication is first approved in China.
This dispels the concerns of enterprises about market competition.
New expectations
With the east wind and favorable policies of the "First Rare Disease Catalogue", the "heat" of China's rare disease market today is not only on the concept.
Foreign pharmaceutical companies have declared rare disease drugs in China. After the acquisition of Shire Pharmaceutical in 2018, Takeda became the world's leader in the treatment of rare diseases, and actively introduced a number of rare disease drugs to China. In the 2021 health insurance negotiations, Takeda's 2 rare disease drugs were successfully included in the medical insurance list.
Shan Guohong, president of Takeda China, believes that it is timely to lay out the use of drugs for rare diseases in China.
Foreign companies such as Sanofi, Roche, and Amgen have also followed step by step, and Bojian's "700,000 one injection" rare disease drugs have been included in medical insurance, which has attracted attention from all walks of life.
A large number of domestic enterprises have also been driven by the research enthusiasm, such as Shufang Pharmaceutical, Deyi Sunshine, Langyu Group, Faith Pharmaceutical, etc., beihai Kangcheng is successfully listed with the aura of "the first share of rare diseases".
In October 2021, Liu Junshuai, vice chairman of the Policy Committee of the China Association for the Promotion of Pharmaceutical Innovation, said at the 6th China Pharmaceutical and Innovation and Investment Conference that the domestic market demand for rare diseases is very strong, and the upward trend is obvious.
Despite certain achievements, the NmPA still believes that there are considerable challenges.
The insufficient level of domestic understanding of rare diseases is the first problem affecting the research and development of rare disease drugs. Without basic research on etiology and pathology, it is impossible to talk about the development of drugs for rare diseases.
In addition, the Drug Review Center also recommends that enterprises should carry out corresponding epidemiological research at the beginning of research and development to obtain reliable data as much as possible.
In terms of rare disease patient registration and epidemiological research, China has launched a national rare disease registration system and established a rare disease patient registration system. The first epidemiological findings of myasthenia gravis have been published, and the screening program for lysosomal storage disorders and the first chondrodyplasia cohort study have been officially launched. There is still a long way to go in these tasks.
As for how to strengthen the basic research on rare diseases, the Health Bureau learned from the 2021 China Rare Disease Conference that the State Food and Drug Administration clearly stated that it should strengthen the linkage and cooperation with various departments.
The peculiarities of rare diseases determine that drug development requires special treatment and management. Xu Xiaoqiang said: I hope to build more communication platforms and provide scientific guidance and help for the research and development of rare disease drugs of pharmaceutical companies.