Attack The "Pseudo Innovation" Of Medicine

On the evening of July 2, Zhang Ze (pseudonym), an investor in the pharmaceutical industry, like many people in the industry, was used to the "see you on Friday" of the regulatory authorities. However, when he came to the "notice on public soliciting opinions on the guiding principles for clinical research and development of clinical value oriented anti tumor drugs" (hereinafter referred to as the "guiding principles") issued by the evaluation center of the State Food and Drug Administration (hereinafter referred to as the "guiding principles"), Zhang's eyes slightly twitched for a moment, and realized that the pharmaceutical industry will cause another huge shock. In a flash, he returned to the announcement on carrying out self inspection and verification of drug clinical trial data, which shocked the pharmaceutical industry in 2015, which was known as "the most stringent verification in history". At that time, a large number of pharmaceutical enterprises withdrew their drug registration applications, which changed the atmosphere of drug listing declaration.

The "head-to-head" comparative test mentioned in the above guiding principles directly reduces the possibility of me too drugs (drugs with their own intellectual property rights, whose efficacy is equivalent to similar breakthrough drugs), thus affecting the number of new drug companies' product projects, and reducing CXO (pharmaceutical R & D and production outsourcing enterprises, including cro / CMO / cdmo, i.e. contract R & D service organization, R & D and cdmo) will be reduced The number of orders available to the company. The share prices of biopharmaceuticals and CXO related listed companies plummeted for three consecutive trading days after the promulgation of the guiding principles.

Although the above companies have stopped falling, people in the industry, including Zhang Ze, understand that some pharmaceutical companies have entered the clinical stage and the newly introduced me too drugs will be "chicken feather in one place". At a recent industry conference, Professor Li Jin, director of oncology Medicine Department of Dongfang Hospital Affiliated to Tongji University, pointed out that the policy to be introduced by CDE this time is to prevent bad capital, cro and pharmaceutical enterprises from jointly digging into the "Wall foot" of "2030 healthy China"“ The government should make top-level design from a higher angle and formulate some regulations or guiding principles. The ideal of "2030 healthy China" can be realized as soon as possible only if the pharmaceutical industry is allowed to embark on a healthy development path. "

Dong Wenzheng, former chairman of the board of supervisors of AVIC foundation and deputy general manager of Wujiahe Molecular Medicine Research Institute Co., Ltd., analyzed to the 21st century economic reporter that there are certain historical reasons for some "pseudo innovation" phenomena in the pharmaceutical industry. Before that, China was in a state of "shortage of medicine and few drugs", generic drugs and "pseudo innovation" came into being, However, in solving the problem of drug accessibility, it also occupies the space for pharmaceutical innovation. Without real innovation, the development of China's pharmaceutical industry will be limited, and it will not be able to stand on the global market without real innovation.

Zhu Xun, an immunologist and distinguished medical expert of New Horizon Capital and Shangyin capital, also stressed that although the guiding principles of this consultation only refer to anti-tumor drugs, the clinical value oriented drug research and development is not only limited to anti-tumor drugs, but also applicable to new drug research and development for all indications. He called on all participants to cherish and gradually move from Heteronomy to self-discipline, so as to form a good ecology of new drug creation in China.

Dong Wenzheng does not deny that there is still clinical value of me too drugs. However, under the background of promoting innovative drugs by the state, pharmaceutical enterprises must make real innovation. They need to do me better (breakthrough and improvement on the existing basis) or even first in class (the first drug that can cure a certain disease). Enterprises without innovation layout may be eliminated, Or try to transform into an innovative pharmaceutical enterprise CMC (chemical, manufacturing and control of drugs) manufacturing enterprises.

In the past two years, the domestic innovative medicine industry has been criticized most for the repeated research and development of a large number of hot targets. Photo by Gan Jun

"Pseudo innovation" piled up

"The biggest pain point of the pharmaceutical industry in the future is innovation. At present, the innovation of the whole pharmaceutical industry in China is still relatively weak. There are only a few truly innovative enterprises, most of which are imitations, and in recent years they are rapid imitations. In this way, we can integrate into the International Ecology, but we can't compete. " Professor Wu Yilong, lifelong director of Guangdong Provincial People's Hospital, pointed out to the 21st century economic reporter at an industry meeting.

According to the data released by CIC Industrial Research Institute, the scale of China's innovative medicine market in 2018 was 128.6 billion yuan, accounting for about 5% of the domestic pharmaceutical market scale; According to IMS heath statistics, in 2015, the market scale of innovative drugs in the United States accounted for 67%, 68% in Japan and 60% in Europe. In contrast, the proportion of China's innovative drug market in the overall scale of medicine was seriously low.

In fact, in the past two years, the domestic innovative medicine industry has been criticized most for the repeated research and development of a large number of hot targets.

For example, car-t cell therapy products are more popular recently. At present, the car-t projects in clinical research mainly focus on the hot targets such as CD19, CD20, CD22, GPC3, BCMA and so on. Among them, more than 40% of car-t clinical trials targeting CD19 in China.

PD-1 (L1) is another serious cluster. On July 5, Lepu biological PD-1 putelimab was accepted by the State Food and drug administration, and became the domestic PD-1 declared for listing in Article 9. In June before this, PD-1 (L1) which had been listed in the domestic market, including Cinda biology, Hengrui medicine, Baiji Shenzhou, mosadon and Roche, were approved for new indications.

Li Jin further pointed out that in addition to PD-1 / PD-L1, claudin18.2 was also found, while the number of gastric cancer and pancreatic cancer patients was not large, but nearly 18 were under development, had been approved and were preparing to declare; In addition, FGFR, tigit, CD19 and even a variety of double antibodies have become the targets of drug companies. From the overall data, in 2020, 77% of the 458 clinical anti-tumor studies were original, which is a great improvement compared with the bioequivalence research conducted by generic drugs before 2014. However, most of them are still modified dosage forms, some are only structural modification, and the curative effect is not improved. Most of them focus on the old targets, so "77% of the original works are original ones with quotation marks".

Wang Yinxiang, chairman of gakos, pointed out in an interview with the 21st century economic reporter that only about 30% of the whole human cells are easy to become drug targets. These targets have been almost done in the past hundred years, and the remaining 70% of the targets are difficult to be made into drugs, which are becoming more and more difficult. This is also the main reason for the research of target clustering.

Li Zonghai, chairman and CEO of Keji pharmaceutical, used "target anxiety" to describe the current situation, and pointed out to reporters of the 21st century economic report: "there are so many natural targets, what should we do if drugs can't find targets? Better targets can only be flocked to, large pharmaceutical enterprises have relevant platforms, they take the strategy of all in (all in) to occupy a place first, which big pharmaceutical enterprise has no antibody? "

Dong Wenzheng pointed out that the "pseudo innovation" caused a waste of resources. Since 2015, the number of clinical trials registered in China has increased exponentially. In 2018, the number of clinical trials in China even exceeded that in the United States and Europe. However, there are a large number of repeated trials and waste of resources in the soaring clinical practice, which exert pressure on the work of the drug supervision department, and occupy the real innovation that needs capital support, which also produces the effect of "bad money drives out good money" for products with clinical value.

In 2020, CDE accepted more than 500 class I new drugs, of which more than 160 were registered for the first time, far more than in the past three years. This is bound to lead to more intense situation of domestic clinical trial resources.

In China, most clinical trials are concentrated in the top research centers in various fields, and the resource distribution is uneven. For emerging Biopharmaceutical Enterprises, due to their late entry into the R & D track and the lack of long-term cooperation with these top research centers, they often do not have an advantage in competing with multinational pharmaceutical companies for limited clinical resources. At the same time, overseas listed drugs are speeding up the application of clinical trials registered in China, which will further squeeze China's limited clinical resources.

Behind the trend

The so-called me too drug is based on the original research and development (transformation) of a similar drug“ Me too medicine is to develop (transform) a similar drug to follow the same road after seeing others go through, which greatly reduces the risk and difficulty. The indications remain unchanged, and only a slight change in the structure of the compound can be made to become a compound, which can avoid patents. " Tang Yanmin, partner of Qiming venture capital, introduced to the reporter of 21st century economic report.

This CDE requires that the clinical trials of anti-tumor drugs should be "head to head trial", which is interpreted as the country's requirement that the follow-up clinical trials should be the commonly known me better in the industry, but in essence, it is also extended from me too drugs. After transformation, its clinical effect is obviously better than the first in class drug.

In 2011, icotinib, a lung cancer targeting drug of Zhejiang Beida Pharmaceutical Co., Ltd., was listed, with the curative effect surpassing that of erlotinib, the original foreign drug. It started the first shot of Chinese generic drugs from "me too" to "me better". Chen Zhu, then Minister of health and academician of Chinese Academy of Sciences, praised as "two bombs and one star in the field of people's livelihood" by Chen Zhu, then Minister of health and academician of Chinese Academy of Sciences, which also greatly stimulated the enthusiasm of domestic pharmaceutical enterprises to develop innovative drugs.

However, for a long time, me too drugs are still the mainstream in China. Pharmaceutical companies are scrambling to enter the market and pile up hot targets. In fact, there are few me better drugs. The real me better needs to rely on clinical trial data. What's more, some me too drugs are not as effective as the drugs before transformation, so they are called "me worse", Peng Jian, former director of CDE No.9 Evaluation Office (mainly responsible for technical review of anti-tumor drugs) and executive vice president of Zejing pharmaceutical development and registration strategy, believes that this will seriously damage the interests of patients.

Song Ruilin, executive director of the China Association for the promotion of pharmaceutical innovation, told the 21st century economic reporter that this is closely related to the weak basic R & D in China.

Sheng Zelin, founder, chairman and CEO of Zejing pharmaceutical, also said frankly that Zejing pharmaceutical has not done first in class, because China's basic science is not in place.

On the innovative knowledge of basic research, song Ruilin pointed out that China still relies on exporting from leading countries, especially the United States. Most of the basic field of modern life science, especially the frontier basic theory and technology innovation, originated from the United States. In China, most of them are improved innovation, which is based on the existing products or technologies, while there are few original theories, technologies and products. For example, in recent years, China has made remarkable progress in gene editing technology, the total number of papers and patents are close to the level of the United States. However, gene editing technology, especially the core patents related to CRISPR / cas9, are basically in the hands of other countries.

In the past five years (2015-2020), the number of drug patent applications and authorizations in China has steadily ranked the top two in the world. Among them, the number of drug patent applications accounted for 28.3% of the global total, while the number of drug patents authorized accounted for 18.1% of the global total. Although the absolute number is high, compared with the total number of patent applications and authorizations in China, the proportion of pharmaceutical innovation related fields is still low. The number of patent applications and authorizations related to pharmaceutical innovation in China accounts for less than 7% of China's total patents, and there is a big gap compared with the proportion of 15% - 25% in Switzerland, the United Kingdom and the United States.

At the same time, song Ruilin also pointed out that the proportion of basic research in China is low. From the perspective of funding sources, the proportion of R & D investment from the government is similar to the level of higher than 20% in the global biomedical leading countries. However, in terms of the use of funds, China's basic research accounted for 6% of the total investment in R & D in 2020, but there is still a significant gap with the level of more than 15% of the global biomedical leading countries; Similarly, the proportion of Applied Research in China in total R & D investment is 11%, which is far behind the average level of nearly 20% of the global biomedical leading countries.

According to wind data and combing the annual report of 2020, it can be found that the R & D share of nearly 400 A-share pharmaceutical companies in China is relatively low. If the absolute amount exceeds 1 billion yuan, only 7 pharmaceutical enterprises, including Hengrui pharmaceutical, Fosun Pharmaceutical, Mindray medical, Junshi biology, Shanghai pharmaceutical, Kelun pharmaceutical and jiankangyuan, are the only pharmaceutical companies. Less than 20% of the companies have R & D expenses over 10%, and less than 10% of the companies have R & D expenses over 15%.

In addition, 132 companies in the chemical preparation and biopharmaceutical industries have a total revenue of nearly 400 billion yuan (excluding the large-scale pharmaceutical business). The total R & D expenses are more than 32 billion yuan, and the R & D expense rate is more than 8%. However, the total sales expenses are close to 120 billion yuan, and the sales expense rate is close to 30%.

Dong Wenzheng pointed out to the 21st century economic reporter that there are historical reasons for the above phenomenon. In the past, in order to solve the problem of lack of doctors and medicines, a large number of imitations were carried out in China. Under this background, pharmaceutical enterprises can also obtain rich profits, which also leads to the fact that Chinese pharmaceutical enterprises have been mainly sales oriented for a long time, with high sales costs. However, some pharmaceutical enterprises are aware of the importance of innovation, and some enterprises begin to lay out the risk of me too / me better with relatively small investment.

There are also capital drivers behind this, including the fake innovation of "license in" (product introduction) which is accelerated by CXO industry. With the help of capital, some small and medium-sized biotechnology companies, virtual companies and individual entrepreneurs quickly introduce early pipelines through this mode, and use mature cro and large-scale domestic patient groups to rapidly promote clinical and commercial application. As "innovative pharmaceutical enterprises", they negotiate to enter the medical insurance catalog, and then realize rapid cash out.

In Zhu Xun's view, innovative medicine is originally a game for a few people, but after some cro companies joined, it has evolved into a game of capital.

Multi sector attack

In fact, this innovative mode of capital + cro has also attracted the attention of the regulatory authorities, and issued new regulations requiring real scientific and technological innovation. Under the new regulations, there are some pure license in project companies at the peak of the first cash withdrawal of the science and technology innovation board. According to the industry analysis, this mode is not easy to pass the examination of the science and technology innovation board.

The above-mentioned new regulations refer to the decision of revising the "guidelines on the evaluation of the attributes of scientific and technological innovation (Trial)" issued by the CSRC on April 16, requiring enterprises that meet the following four indicators to apply for listing on the science and Technology Innovation Board: R & D investment accounts for more than 5% of the operating revenue in the past three years, or the R & D investment amount in the past three years has exceeded 60 million yuan; The proportion of R & D personnel in the total number of employees in that year shall not be less than 10%; More than 5 invention patents have formed the main business income; The compound growth rate of business income in the last three years has reached 20%, or the amount of business income in the latest year has reached 300 million yuan.

"The CSRC resents these cases of rapid wealth creation, especially when the fund takes out a sum of money to find two people, buy two products, and immediately save a company, which quickly changes from zero to tens of billions of market value, which is not conducive to real innovation. Everybody's going to make quick money, and it's not sustainable. " Tang Yanmin pointed out to the 21st century economic reporter.

In addition to the China Securities Regulatory Commission, the National Health Commission has also put forward further standards for the use of cancer drugs in clinical practice.

On June 28, the National Health Commission Medical Administration Bureau issued the notice on the management indicators of rational clinical application of anti-tumor drugs (2021 version) (hereinafter referred to as the "notice"), involving six indicators such as the utilization rate of anti-tumor drugs of restricted use level and ordinary use level, and the proportion of anti-tumor drugs used.

According to the notice of the National Health Commission, the use of newly marketed cancer drugs, as well as anti-tumor drugs with high price and heavy economic burden, will be listed as restricted use. When the utilization rate of anti-tumor drugs with restricted use level increases significantly, the rationality of drug use should be evaluated. This is not a big positive for the admission of anti-tumor drugs from innovative pharmaceutical enterprises.

In Li Zonghai's opinion, innovative drugs, especially cancer drugs, are expensive. Therefore, how to reduce costs and improve patients' affordability is the key.

The person in charge of Lilly Asia Fund also pointed out that there is a certain contradiction between the cost, pricing and the affordability of patients“ Cell therapy is a kind of special drug, and the patient's expenditure should be considered when calculating its value. If cell therapy can bring long-term benefits and even cure some patients, it will be different from the traditional scenario of continuous medication. On the other hand, cell therapy companies themselves are constantly innovating and making progress, reducing costs, improving accessibility, and even moving towards allogeneic cell therapy. " The person in charge pointed out.

Li Zonghai also told reporters of the 21st century economic report that on the one hand, enterprises need to reduce costs; on the other hand, under the existing medical insurance payment system, it also needs a variety of payment methods, such as the addition of commercial insurance.

The CSRC is stuck in the channel, and the health commission Snipes from clinical and admission (price), while this CDE is to seize the source. This sniping war will bring direct promotion to China's source innovation.

"The CDE document on July 2 shocked the pharmaceutical industry as much as the" July 22 audit storm "of that year." An investor who has been following the pharmaceutical industry for a long time pointed out to the 21st century economic reporter.

"July 22 audit storm" is still fresh in the memory of pharmaceutical industry investors, and "tragedy" and "storm" are the core words. A clinical trial data verification announcement "Notice of the State Food and Drug Administration on the self inspection and verification of drug clinical trial data (2015 No. 117)" is known as "the most stringent data verification requirements in history", It stirred up the whole pharmaceutical industry, involving pharmaceutical enterprises, cro companies and clinical trial bases.

The "7.22 audit storm" is aimed at large-scale data fraud of drugs. As a direct result, more than 85% of the so-called "new drugs" withdraw their applications.

This time, the CDE is aimed at cancer drugs. The core content is to require new drug research and development to "take the patient's needs as the core and clinical value as the guidance", and focus on the problems such as the current domestic innovative drug target clustering, "me too" flooding, low-level duplication, lack of real innovation and so on.

CDE pointed out that at present, the research and development of anti-tumor drugs in China is in the stage of rapid development. New treatment methods further extend the survival period of cancer patients, and malignant tumors show a trend of slow disease, which makes cancer patients have higher expectations for the safety of drugs, treatment experience and quality of life, as well as the experience of tumor subjects in clinical trials.

In Li Zonghai's opinion, the above-mentioned CDE guidelines will reduce unnecessary waste of medical resources and funds for cancer, and better promote the development of innovative drugs. It should be beneficial to Keji pharmaceutical and other enterprises based on the development of innovative drugs to meet the needs of cancer patients.

In March 2016, the former State Food and Drug Administration issued the work plan for the reform of chemical drug registration classification, which upgraded the definition of new drugs from "China new" to "global new", indicating China's determination to be a truly innovative drug.

Xu Jinghe, deputy director of the State Drug Administration, told reporters of the 21st century economic report at a previous industry conference that China's drug regulatory authorities have always regarded the internationalization of supervision as one of the important paths for China to realize the transformation from a big pharmaceutical country to a powerful pharmaceutical country.

According to the "healthy China 2030 planning outline" released in October 2016, China will step into the ranks of world pharmaceutical powers by 2030.

Xu Jinghe said that China's drug regulatory authorities have actively promoted the implementation of China's drug regulatory action plan, established 12 regulatory scientific research bases, the first batch of 9 projects, studied and developed 103 new tools, methods and standards, including 31 issues, selected 117 national key laboratories, and led the establishment of an innovation and cooperation platform for artificial intelligence medical devices and biomaterials, More resources and strength should be organized to support the innovation and development of pharmaceutical industry and the improvement of drug regulatory capacity.

Clinical value orientation

Although the above CDE guidelines were not officially implemented, the reaction of listed companies related to biopharmaceuticals and CXO in the capital market immediately appeared, especially the share prices of CXO related listed companies fell sharply for three consecutive trading days.

For the performance of the market, Chang Jianqing, vice president of TEG pharmaceutical policy and regulation affairs, thinks it is "incredible": the positive efforts of the drug evaluation center should have been applauded by the industry. How could it be completely misunderstood by the market?

Chang Jianqing pointed out that "clinical value oriented" is not a new word. As early as 2015, the State Council issued the "opinions on the reform of the drug and medical device review and approval system" (i.e. No. 44 document), which clearly pointed out that: encourage clinical value oriented drug innovation, optimize the review and approval procedures of innovative drugs, and accelerate the evaluation of innovative drugs that are urgently needed in clinical practice; For the application of clinical trial of innovative drugs, the clinical value and subject protection should be reviewed.

Chang Jianqing pointed out to the reporter of 21st century economic report that this guiding principle is a phased summary of the exploration, practice and accumulation of anti-tumor drug review and approval for nearly six years, and released in the form of transformation into guiding principle, so as to better help the application enterprises understand that the research and development of anti-tumor drugs should be based on clinical value rather than for research and development.

"The guiding principles also mentioned that new drugs with mechanism of action and target follow-up, continuous improvement of safety and improvement of dosage forms or administration methods to improve treatment experience and convenience are also innovations, which may be more in line with our development stage and can bring clinical value to patients." Chang Jianqing pointed out.

Peng Jian believes that the clinical value is based on the needs of patients in the process of clinical practice, which is specifically reflected in: whether there is an existing treatment, how effective is the existing treatment, what is the safety of the existing treatment, the clinical adaptability or experience of the existing treatment, and whether the patients can afford it. From the perspective of the guidelines, the clinical value includes effectiveness, safety, compliance and accessibility, and the four aspects that have been improved are called the best“ For the research and development of tumor drugs, we should pursue better treatment, because the first demand of cancer patients is survival. "

From a practical point of view, some rational capital also began to focus on the above-mentioned angle of layout.

For example, when the capital including the Lilly Asia Fund mentioned above makes relevant investment, the efficacy, safety and actual benefits to patients of the drug are taken into consideration. Compared with the past, "hot money" blindly entered the "innovation" track, now more capital also began to tend to be rational, some capital and market also began to realize the "pseudo innovation", "hot target" and "crowded track" of Chinese medicine. As a matter of fact, some pharmaceutical companies have been listed in Hong Kong stock market, which seems to be a curse in the past two years. Some biomedical stocks broke out as soon as they were listed, and their stock prices kept falling.

"Breaking through" was once interpreted by the market as the "touchstone" of real innovation and sustainable development. For example, Keji Pharmaceutical Co., Ltd. broke out on the day of listing, which was interpreted as the fierce competition of BCMA targets, the affordability of car-t drugs, and the slow progress of clinical / commercialization.

In this regard, Li Zonghai told reporters of the 21st century economic report that he did not worry too much about the breakout. He believed that this was actually a misreading of the capital market, and it would take some time for the market to understand the products.

Li Zonghai, for example, said that car-t products are in phase I clinical practice, which seems to be very early, but it is not the case. "We have reported the second stage clinical practice for solid tumors, and at present, the sample size entering phase II is relatively small, so the whole product development cycle is much shorter than that of traditional drugs."

Guo Zhigang, a professor at the school of life sciences of Nanjing Normal University, who is engaged in car-t and cellular immunotherapy, also pointed out that for traditional drug research and development, the effectiveness of drugs is usually considered first, and then the safety is considered. However, car-t directly attacks the target cells, which is usually effective. Therefore, the most important consideration of car-t in the R & D phase is security.

How to go in the future?

Dong Wenzheng pointed out to the 21st century economic reporter that the above-mentioned clinical value orientation is also in line with international standards. This guiding principle echoes the guiding principles for clinical drug development of FDA in 2017 and ICH in 2020, and further promotes the standardization of clinical research on tumor drugs in China.

In 2017, the U.S. Food and Drug Administration issued a plan to develop patient-centered drug development guidelines. In November 2020, ICH adopted a patient-centered issue paper on drug research and development, which developed guidelines for the collection and analysis of patient information feedback and the development of tools. China joined ICH in 2017 and further became a member of the management committee in 2018, and was re elected not long ago.

What should PD-1 do under the background of target clustering, track congestion and conformity with international rules?

Dong Wenzheng believes that exploring the joint application scheme with new drugs is one of the future ways to expand more extensive indications and actively explore the global market or lay out related track enterprises in the future.

It is understood that the four domestic PD-1 models that have been put on the market have been approved new indications during this period, and actively carry out joint drug test with other enterprise products.

"In fact, this is still based on the above mentioned clinical value. On the one hand, it is necessary to explore different combinations of drugs for different patients; On the other hand, we should also pay attention to the unmet clinical needs. These two points may become the competition space for the enterprises entering the market or the products already listed. " Dong Wenzheng pointed out.

Yang Dajun, chairman and CEO of AXA pharmaceutical, pointed out that PD-1 may be a special case. Although the PD-1 of Baiji Shenzhou is the fifth listed product in the United States, it still has clinical demand or market demand, including combination therapy, etc., so Novartis still spent $2.2 billion to buy it. But at the same time, Yang Dajun also pointed out a practical problem: PD-1 is very smooth now. When it comes to the market, it is already the 10th. What else do you sell? Do not do the clinical phase III or to go on the market, only to find that the competitor drugs are better and cheaper, and it will be too late to sell on the market.

As a matter of fact, Yasheng pharmaceutical has encountered a similar situation“ As early as 2015, Yasheng pharmaceutical's c-met layout was still very new, which was in the top 10 of that year, but the clinical data behind it was very difficult to do. When we went back to do c-met screening, three others had already come to the market, and we were already late. " Yang Dajun particularly stressed that in this case, enterprises must adjust their direction as soon as possible.

It is understood that not long ago, on the occasion of the 50th anniversary of Hengrui pharmaceutical, Hengrui pharmaceutical has announced the termination of the research and development of claudin18.2 (molecular target of antigenic gastric cancer and pancreatic cancer drugs), which is the first phase of clinical trial. As of the end of April 2021, there are about 25 domestic drugs targeting claudin18.2, including monoclonal antibody, double antibody, ADC and car-t. among them, 14 drugs have entered the clinical stage (including IIT initiated by researchers), but there are fewer patients with primary gastric cancer and pancreatic cancer in China.

Soochow Securities believes that at present, China is in the process of transforming from fast follow to first in class. The release of guiding principles makes the labor period of industry transformation come earlier, which is more conducive to the change of innovation environment, and forces pharmaceutical enterprises to accelerate innovation. In the future, me better will be more favored by the review.

Dong Wenzheng believes that the above-mentioned guiding principles of CDE actually accelerate the pace of pharmaceutical enterprises to return to rationality, "stop loss in time", and there will be "differentiation" in the development of enterprises in the future“ Under the drug holder rule, enterprises that did not actively deploy truly innovative drugs may transform into CMC of innovative drugs in the future. "

Zhu Xun stressed that the current biotech needs to transform from a small company with a substantial scale and a large company with a virtual high market value to a substantial large company to support its market value. Biotech must complete the sublimation, break out of the current dilemma of me too, me better, biosimilar, fast follow, and develop from license in to license out, from Greater China market to global market, and from current highly homogeneous to differentiated unmet clinical needs.