Improving The Threshold Of Innovative Drugs: CDE New Deal Focuses On R & D Homogeneity, Pushing "China'S First Initiative"

It is beneficial to eliminate many homogenized me too products and select more high-quality first in class drugs.

On July 6, the pharmaceutical sector collectively "dived" to lead the decline of a shares, while Fosun Pharmaceutical, TEG pharmaceutical, Yaoming Kant, Tongce medical and other industry leading stocks with a market value of more than 100 billion yuan appeared "flash collapse".

In view of this abnormal phenomenon, the industry believes that the cause may be the "notice on Soliciting Opinions on the guiding principles of clinical value oriented clinical research and development of anti-tumor drugs" (hereinafter referred to as the draft) issued by the drug evaluation center (CDE) of the State Drug Administration on July 2.

"Opinion draft" clearly pointed out: new drug research and development should provide patients with better treatment options as the highest goal, when the non optimal treatment is selected as the control, even if the clinical trial reaches the preset research goal, it can not show that the trial drug can meet the actual needs of patients in clinical practice, or can not prove the value of the drug to patients.

In response to this policy, Jin Chunlin, director of the Shanghai Health and health development research center, said in an interview with the 21st century economic report: "the CDE draft will standardize and really enhance the R & D strength of pharmaceutical enterprises from another level. After the introduction of this policy, it will help to improve the research and development standards of domestic innovative drugs, make the clinical data standards submitted by innovative pharmaceutical enterprises refer to the best tumor innovative drugs in the market, greatly improve the quality of innovative drugs, let the innovative products of truly innovative pharmaceutical enterprises be used for cancer patients, and eliminate many homogenized me too products, Select more high-quality first in class drugs. "

In other words, the current CDE move will help to strengthen the R & D strength of China's innovative pharmaceutical enterprises, and change the phenomenon of homogenization of innovative products. In the future, improving the R & D strength of enterprises will also become the focus of the national drug regulatory department in the next stage.

The new policy of CDE encourages truly valuable innovative anti-tumor drugs to enter clinical trials and submit for approval and listing. Visual China

Innovation and standardization of R & D standards

It has to be said that the draft has already been published. As early as in the 2018 "CSCO CDE China's original anti-tumor drugs" forum, Yang Zhimin, director of the first clinical department of CDE chemical drugs, pointed out in the report that from the list of anti-tumor drugs approved by China from 2011 to 2018, the number of approved anti-tumor drugs has increased significantly in recent two years, and the acceleration of review and the implementation of priority review policy are the most direct influencing factors, 67% and 100% of the approved drugs in 2017 and 2018 (as of September) were given priority review.

"On the whole, there are the following outstanding problems in the research and development of anti-tumor drugs in China at this stage: first, although the independent research and development ability of anti-tumor drugs in China has been significantly enhanced, most of them are still learning from foreign targets and models; Second, the phenomenon of clustering is prominent, such as the emergence of a large number of anti PD-1 immunotherapy products in recent years; Third, basic data (such as epidemiology) are seriously insufficient, and basic research needs to be improved; Fourth, the research and application of scientific methods and tools need to be strengthened, especially the use of model simulation and innovative methods Yang Zhimin once said so.

And this time, the industry also agreed that solving the current situation of innovative drugs clustering has become the focus of the CDE "opinion draft".

Sorting out the R & D pipeline of PD-1 immunotherapy enterprises in China, it is not difficult to find that the R & D of domestic innovative products has made rapid progress, but it is also a serious pile up, which is another side of the coin, high-level repeated R & D investment and abuse. At present, in the market of PD-1 immunotherapy, the race track is too crowded, which directly leads to serious homogenization.

As of April 18, 2021, about 72 PD-1 related varieties are in the stage of R & D / approval in China, according to the data of MI Nei net. According to the clinical trial data, as of September 2020, there are 4400 clinical trials of PD-1 / PD-L1 mAbs in the world. Compared with September 2017, the total number of clinical trials of PD-1 / PD-L1 mAbs has increased three times.

In addition, domestic pharmaceutical companies also have the same problem in the research of target. Take car-t cell therapy products which are more popular recently as an example. At present, car-t projects in clinical research mainly focus on popular targets such as CD19, CD20, CD22, GPC3 and BCMA. Among them, in China, the proportion of car-t clinical trials targeting CD19 is more than 40%, and the clinical trials targeting CD20, CD22 and GPC3 are less, and the proportion of clinical trials with BCMA targets is even only 5%.

"In recent years, the number of approved cancer drugs in China has been too large, leading to the emergence of many drugs. As for PD-1 drugs, hundreds of domestic pharmaceutical enterprises are laying out clinical research and development, but behind this is actually disordered competition, which is boosted by capital. This is not a good phenomenon“ Jin Chunlin told reporters of the 21st century economic report.

In the collective "flash collapse" of the pharmaceutical sector on July 6, Fosun medicine and Yaoming biology attracted much attention. Not long ago, Fosun KITT's first car-t cell therapy was officially approved, which made Fosun Pharmaceutical A-share trading limit and H-share up nearly 10%. On July 6, Fosun Pharmaceutical was the first to drop its limit, but the trading was opened at the end of the day and ended down 9.64% (a share). And Yao Ming Kant (A-share) in the cro concept stocks of the situation, also hard to avoid, once hit the limit.

In this regard, the person in charge of Fosun Pharmaceutical told the 21st century economic report that "the core of this round of medical reform is to take clinical value as the orientation of patient's diagnosis and treatment needs. The purpose of CDE's" opinion draft "is to eliminate the false and retain the true, encourage truly valuable anti-tumor innovative drugs to enter clinical trials and submit for approval for listing, and guide the rational allocation of innovative R & D resources, At the same time, it also provides more scientific basis and technical support for new drugs to enter medical insurance negotiation and serve clinical use

Dr. Chen Zhisheng, CEO of YaoMing biology, also told reporters of the 21st century economic report: "it is mentioned in the draft that new drug research and development should provide patients with better treatment options as the highest goal. This actually raises the threshold of innovative drugs, avoids the homogenization competition of popular target drugs such as PD-1 in the domestic market, and is good information for the "head" enterprises in the industry who are really engaged in innovative research and development. "

Research and development process or slow down the first in class will be the main direction of attack

The research and development of drugs has not affected the approval progress of domestic innovative drugs.

In the first half of 2021, the State Drug Administration (nmpa) approved the listing of a number of innovative therapies, including the Fosun Kat car-t cell therapy product achirensai injection, the class 1 innovative drug pamipali capsule declared by Baiji Shenzhou, weidixitumab for Rongchang biopharmaceutical injection, and donafinil toluenesulfonate tablets, which were applied by Zejing Biopharmaceuticals. As of June 30, 2021, 15 domestic class 1 new drugs have been approved in China, while according to the 2020 annual drug review report, only 4 domestic class 1 new drugs have been approved in the same period of last year.

In 2020, CDE completed 11582 applications for registration of traditional Chinese medicine, chemical drugs and biological products, an increase of 32.67% compared with that in 2019. Among them, 8606 registration applications requiring technical review were completed, an increase of 26.24% compared with that in 2019; 2972 applications for direct administrative examination and approval were completed. In addition, the center has realized the timely review and approval rate of all kinds of registration applications for traditional Chinese medicine, chemical drugs and biological products, with a record high of 94.48%.

However, in this process, many me too products have accelerated to enter the Chinese market“ It is a good thing to accelerate the development of innovative drugs in China, but whether these innovative drugs can meet the real needs of different patients needs to be further weighed. But it is certain that the issuance of this policy will cool down the market of innovative drugs, slow down the approval process of innovative drugs, and give more treatment schemes with real clinical value good opportunities. " Jin Chunlin said.

In Jin Chunlin's view, the decline of pharmaceutical stocks was mainly affected by the policy of CDE and other factors. For example, due to the influence of patent related laws and regulations, many domestic traditional pharmaceutical companies which mainly focus on imitation are unable to continue the research and development of related drugs. These drugs not only involve cancer drugs, but also involve many therapeutic drugs in other disease fields. This is also an important reason why the pharmaceutical stocks fell in the whole line this time.

In fact, in recent years, with the rapid progress of generic drug quality and efficacy consistency evaluation, the overall pattern of China's pharmaceutical industry has been restructured. The policy brings structural opportunities for high-quality generic drugs, so as to ensure the accessibility, safety and effectiveness of drugs more reasonably. But this is far from enough. The real first in class innovative medicine is the ultimate discovery of the industry development. In other words, in the near future, generic drugs and me too drugs will be gradually eliminated, and first in class and best in class drugs will become the mainstream in China.

The above-mentioned personages of Fosun Pharmaceutical and Yaoming bio revealed that the follow-up first in class will be the focus of the company. Fosun Pharmaceutical said that the research project will focus on the global cutting-edge technology, introduce the latest breakthrough technology and products, and fill in the field where there is no effective therapy. At the same time, it is committed to the breakthrough of first in class, aiming at the latest target, developing best in class products.

Yao Ming bio believes that in the future, the domestic biopharmaceutical industry may be divided into two ecological circles, one is composed of head enterprises which focus on "first in class" innovative drug research and development and are guided by unmet clinical needs, and the other is a basic ecosystem composed of enterprises with weak innovation ability and low price competition, At present, the guidance of domestic policy will be more and more conducive to the development of the former.

In the face of the stock price shock, some industry insiders said that this is not temporary, and the follow-up policy will cause long-term fluctuations in the pharmaceutical industry. On this, some investors have given the opposite view.

"At present, the industry has over interpreted the policy of CDE," Dr. Zhao Bing, head of Huaxing Securities Research Institute and chief analyst of pharmaceutical industry, said in an interview with 21st century economic report. The core of CDE's policy is to solve the current situation of innovative therapy research and development in the market, hoping to further guide the efficient use of R & D resources. In addition, from the perspective of pharmaceutical investment and financing, the market is optimistic about the pharmaceutical market, so it will not bring about subsequent big shocks. As for why this stock price fluctuation occurs, it is actually due to the joint action of many factors including centralized purchasing and medical insurance. "