Can Me Too Drugs Still Be Made In The Fierce Competition Of Homogeneity Of Chinese Pharmaceutical Enterprises?

"Under the influence of overseas returnees' entrepreneurial trend, capital pursuit, preferential policies of local governments, and continuous maturity of cro / cdmo supporting facilities, as well as the model effect of license in mode and Vic mode, domestic companies can quickly replicate. 18a and the science and technology innovation board provide exit channels for capital and accelerate capital inflow. Driven by all factors, the threshold of innovative drugs is gradually lowering." On August 2, Li jiakui, CEO of xuanzhu Biotechnology Co., Ltd., said at the sub forum of the national pharmaceutical industry information annual meeting.

He analyzed that innovative medicine is a high-tech, high investment, high-risk industry, not everyone can enter, but now many enterprises are entering, and some without innovation ability also come in, which causes the following three problems.

First, lack of source innovation and serious homogenization competition. For example, there are hundreds of pharmaceutical companies in PD-1 track, more than 50 pharmaceutical companies have applied for clinical application in EGFR, and nearly 40 enterprises in claudin18.2 are queuing up; Second, the resources are wasted, the clinical patients are not enough, there is a phenomenon of robbing patients, low-level duplication causes waste of research and development costs; Third, the price of the license in project is surging up. The down payment of the clinical ia project reaches more than 10 million US dollars, and the number of good projects has soared to tens of millions of US dollars. There are fewer and fewer license in projects.

"We compete with each other to raise the price. After bringing the project back for development, we have to face medical insurance bargaining. How can commercial returns be realized?" Li jiakui said.

Can me too drugs still be made?

In this context, on July 2, the evaluation center of the State Food and Drug Administration issued the notice on public soliciting opinions on the guiding principles for clinical value oriented clinical research and development of anti-tumor drugs (hereinafter referred to as the guiding principles). The "head-to-head" comparative test mentioned in the notice directly reduced the possibility of me too drugs to go on the market The share prices of CXO related listed companies plummeted for three consecutive trading days after the promulgation of the guiding principles. Whether me too drugs belong to pseudo innovation has aroused heated discussion.

According to Li jiakui's analysis, the guiding principles mentioned two points: one is to be guided by clinical value; the other is to provide patients with the best treatment options as the goal, which has played an important role in correcting the development direction of China's future innovative drugs. At the same time, it has also triggered a lot of discussions on me too innovative drugs in the industry, and there have been many attacks.

So, reviewing the ten years of innovative drugs in China, how to evaluate me too drugs correctly?

Some people believe that both FIC (first in class) / BIC (best in class) drugs or me too drugs have clinical value. Even if the clinical value of me too drugs is not prominent compared with the same kind of drugs, it can reduce the drug price and benefit the patients, but at the same time, how to balance the scientific risk and commercial risk has become an important problem.

According to Li jiakui, referring to the development experience of other countries, Japan has gone through a 10-year me too stage and then moved towards international innovation. In fact, large multinational pharmaceutical enterprises also do me too, and there are many cases, mainly because these enterprises have business culture“ Generally speaking, for the same target, the first three have a market, and the fourth and fifth don't make much money. Therefore, after going to the five companies, they usually have to rely on market means, and the latter enterprises seldom follow suit. However, for China, the current phenomenon reflects that the enterprises are not mature enough and have no overall consideration. "

So can me too drugs continue to do?

Li jiakui believes that me too drugs have opened up the system of innovative drugs in China, promoted the establishment and improvement of laws and policies, partially alleviated the difficulties of patients in medication, and also reduced the burden of national medical insurance“ At present, it is the general direction to advocate source innovation, which is certainly correct. However, source innovation comes from the long-term accumulation of basic research. It is not to say that we advocate source innovation today, and all pharmaceutical companies will do source innovation tomorrow. At present, in the absence of source innovation, if we do me too, we should scientifically evaluate whether we have achieved product differentiation, whether we have achieved the goal of product differentiation Whether there are product advantages, clinical value and commercial returns, we should be cautious when we have 40 or 50 enterprises with one target. "

Wang Qiwei, senior industry researcher of China Pharmaceutical Industry Information Center, also analyzed the target innovation strategy in the forum. According to the data provided by Wang Qiwei, the number of generic names of new drugs in China increased rapidly from 99 in 2015 to 763 in 2020, and the number of new drug acceptance increased rapidly from 235 in 2015 to 1768 in 2020.

Regarding the target problem, Wang Qiwei said that there are two strategies for selecting new global targets: the first is to select new targets with sufficient potential, and attention should be paid to the progress of research and development, the innovation of domestic original drugs and the risk of R & D; The second is to select new targets with successful experience, which needs to pay attention to the market trend and the layout of indications. The top 20 targets with the largest number of approved drugs in the world or in China need to be carefully arranged.

"In fact, the original intention of all target innovation is clinical needs. The purpose is to solve the clinical needs, and target innovation is only the means." Wang Qiwei said.

Basic research is weak

After 15 years of development, the United States has overtaken Europe in an all-round way in the mid-1990s, becoming the largest biopharmaceutical country in the world. At present, 57% of the global innovative drugs come from the United States.

Li jiakui said that analyzing the main factors of the rapid development of biopharmaceutical innovation in the United States, the first is the huge investment in basic research, and then comes the strong protection and enforcement of intellectual property rights, the coverage and payment policies supporting and encouraging innovation, the well functioning and science-based regulatory system, and the perfect capital financing channels.

For basic research investment, R & D investment intensity is the main index to measure the industrial technology development ability, which reflects the industry's investment in innovation activities. R & D investment intensity usually refers to the proportion of R & D funds in total output value, main business income or industrial added value.

According to the data shared by Li jiakui, the US federal government invested 310.32 billion yuan in basic research in fiscal year 2022, accounting for 27% of R & D expenditure. China's investment in basic research in 2019 was 133.56 billion yuan, accounting for more than 6% of R & D funding for the first time.

Li jiakui believes that high-level scientific research institutions are the cornerstone of basic research. The biomedical industry in the United States is based on biotechnology, with universities and research institutes as the starting point. Scientific research institutes provide a large number of basic research results, key technologies and talents for the biomedical industry. In contrast, the domestic pharmaceutical industry is mainly guided by policies, and local governments have built biomedical industrial parks. Due to the lack of basic research from scientific research institutes, the innovation output may be affected.

Relevant researchers of China Biotechnology Development Center have also published an analysis and said that, unlike the relatively dispersed target distribution of global new drug creation, China's target concentration is very high, and one third of the drugs under research are concentrated in the top 10 hot targets. The reasons are: on the one hand, the accumulation of basic research on new drug creation is relatively weak, the layout of applied basic research is insufficient, and the basic research achievements such as new targets, new mechanisms and new methods are lack; On the other hand, there is a lack of serial basic research and application basic research oriented by new drug achievements.

The source of developing original new drugs lies in theoretical innovation and breakthrough, which requires long-term and solid accumulation of basic research. Once a theoretical breakthrough is made in the pathogenesis of a disease, a batch of original new drugs with important clinical application value will be produced. For example, the breakthrough in basic research of immune checkpoint has triggered a wave of tumor immunotherapy and cell therapy. PD-1 / PDL-1 antibody and car-t cell therapy have saved the lives of countless patients with advanced cancer.

Li jiakui said that from discovery to approval of new drugs is a long process, with high cost and high risk. According to NIH statistics, 80% - 90% of research projects fail before human testing. The average cost of developing a new approved drug is more than $1 billion, and the cost of research and development will double every nine years. The contradiction between the high-risk investment and huge R & D expenses of pharmaceutical enterprises and the limited payment ability of medical insurance will be more and more prominent.

Therefore, it needs the efforts of various industries: for enterprises, it is necessary to boldly try new innovation modes, apply new technologies, improve R & D efficiency and reduce R & D costs; For the policy, we should establish a win-win innovative payment system to continuously cultivate pharmaceutical innovation groups with long-term innovation motivation; For capital, we should be brave enough to support the revolution of R & D disruptive technology; For business, it is necessary to establish and improve multi-level medical insurance, especially commercial insurance.

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