Recently, the Center for Drug Evaluation (CDE) of the State Drug Administration released the "Annual Report on the Status of Clinical Trials of New Drug Registration in China (2020)" (hereinafter referred to as the "Report"), which is the first comprehensive summary of the current status of clinical trials of new drug registration in China. An analysis report.

Behind this "hot" report, some issues have also triggered cold thinking in the industry.

Homogenization "internal volume", waste of resources should not be underestimated

The "Report" data shows that in 2020, a total of 2,602 clinical trials were registered on the drug clinical trial registration and information publicity platform, but the top 10 targets of registered clinical drug varieties were PD-1, CYP51A1, VEGFR, PD-L1, DNA , EGFR, microrubule, HER2, GLP-1R, JAK1, with a total of 389 varieties, accounting for more than 10%.

Judging from the number of clinical trials, the number of clinical trials of the above-mentioned TOP10 targets is also very concentrated. Among them, there are more than 60 clinical trials for PD-1, VEGFR, PD-L1 and other targets, and more than 60 clinical trials for PD-1 targets. of nearly 100 items.

In addition, from the perspective of indications, clinical trials are mainly concentrated in the fields of anti-tumor and anti-infection, and the indications of clinical trials of biological drugs and chemical drugs are mainly anti-tumor, accounting for 42.1% and 47.3% respectively.

It is not difficult to see that the homogenization of new drug clinical trials is seriously "invoked". Domestic clinical resources compete fiercely in tumors and popular targets.

However, some industry insiders have previously analyzed that the phenomenon of "homogenization" will cause some waste of clinical resources. Take PD-1 as an example, there are currently 6 products on the market across the country, and they are hot in terms of indication exploration and commercialization strategies. In the latest round of medical insurance negotiations, the price of the online version of PD-1 seems to have been controlled at 30,000 to 40,000 yuan a year. However, there are still more than 100 clinical trials in progress, so the research and development of "homogenization" is like a chicken rib.
 
It is not difficult to see from here that disease selection and target establishment are like choosing a race track. If you choose the right disease and target, the speed of research and development may only be the size of the value. If you choose the wrong target, all the efforts will be in vain.

Image source: CDE 2020 China New Drug Clinical Trial Report

Image source: CDE 2020 China New Drug Clinical Trial Report

At the same time, there is another data worth paying attention to in the "Report": "Regarding the scope of trials, only 91.6% of the drugs have been clinically tested in China." That is to say, international multi-center trials only accounted for 8.1% (210 trials). Compared with the number of companies shouting "Sino-US dual newspapers" and "global clinical" in the capital fever, the number of clinical clinics that really put their products on the global competition track is slightly stretched.

Second, the efficiency of clinical advancement is worrying. According to the data of the "Report", of the 1,473 clinical trials of innovative drugs registered in 2020, less than half (45.4%) of subjects were recruited within one year after the IND was approved. The clinical trials completed in 2020 are still dominated by Phase I clinical trials, with an average completion time of 95.7 days; only 5 Phase III clinical trials have been completed, with an average completion time of 176.6 days. It is not difficult to see that at present, more than half of the new drugs in China do not start new drug clinical trials more than one year after obtaining the IND approval, but almost all of them will enter the phase I clinical stage within three years.

Third, the proportion of pediatric drug clinical trials is relatively low. Among the 1,473 clinical trials, 129 were clinical trials involving children, accounting for 8.8%. A total of 33 new drug clinical trials conducted only in children were registered, accounting for only 2.2% of the total new drug clinical trials, and the main indications were anti-tumor drugs and vaccines. The reason for the low R&D enthusiasm is that the clinical trials of pediatric drugs have long cycles, difficulty in recruiting subjects, and high safety risks.

Fourth, the geographical distribution of clinical trials is uneven. After the qualification of clinical trial institutions in my country was changed from the certification system to the filing system, although more medical institutions are encouraged to participate in clinical trials, the geographical distribution of clinical trials is still not balanced. In the domestic clinical trials of new drugs, institutions in Beijing, Jiangsu Province and Shanghai still participate in more clinical trials.

Differentiated competition may be the key to breaking the game

The layman watches the fun, the layman watches the doorway. Behind the data, we have already seen that the gap between domestic new drug research and development and foreign clinical practice is further narrowing, but there are still problems such as clustering of targets, concentrated indications, "surplus" and "shortage". From the perspective of clinical R&D and evaluation, clinical value-oriented innovation and R&D is always a core issue. Simply put, it is "necessary only when there is a need". The key to breaking the differentiated competition.

In fact, "drug research and development should focus on patient needs and be guided by clinical value" has long been a general consensus in policies and regulations. Previously, Guo Fa [2015] No. 44, "The State Council's Opinions on Reforming the Review and Approval System for Drugs and Medical Devices" pointed out that "to encourage clinical value-oriented drug innovation". The ICH adopted the Patient Focused Drug Development (PFDD) issue paper in November 2020. In July this year, the Center for Drug Evaluation (CDE) of the State Drug Administration issued the "Notice on Publicly Seeking Opinions on the Guiding Principles of Clinical Research and Development of Antitumor Drugs Oriented to Clinical Value", clearly stating that new drug research and development should provide patients with better Excellent treatment options are the highest goal. The introduction of the draft also means that starting from the research and development of anti-tumor drugs, the clinical value-oriented drug research and development implemented by the state over the years will affect the entire industry and the entire disease field, which will have far-reaching significance.

At the 6th China Pharmaceutical Innovation and Investment Conference (CBIIC) held not long ago, Yang Zhimin, director of the Department of Clinical Medicine of the Drug Evaluation Center of the State Drug Administration, also said: "Whether it is review and approval, or drug research and development, , we should turn our attention from drugs to people. PD-1 has been clinically approved for more than 100, and it is not said that new PD-1 drugs will no longer be approved in the future. If our focus is on drugs, it must be more How many drugs have been on the market. We compare people, that is, pay attention to the treatment indications. If there is no drug for this indication and no one does it, then a new PD-1 is declared to be able to treat it, why not approve it? "

At present, a considerable number of leading innovative pharmaceutical companies have begun to develop their R&D pipelines based on "clinical value". For example, the world's first subcutaneous PD-L1 inhibitor KN035 (envolimab), which is about to be launched by Corning Jeremy, has been launched. Optimize the way of administration in the dosage form to help patients reduce the pain of treatment.

Seize the leading position in clinical research and development

In response to the problem of low clinical efficiency, it has always been a "heart disease" in the pharmaceutical industry. 10 years, 1 billion investment, 10% success rate is often used to describe the difficulty of a new drug to market. In this regard, Dr. Ye Xiaoping, co-founder and chairman of Tigermed, said that as an important link in the process of new drug research and development, clinical trials are a highly complex process. With the vigorous development of my country's innovative drug industry, it is necessary to ensure the quality of trials. , while improving efficiency, digitalization is one of the most powerful means.
  
In addition, Zheshang Pharmaceutical Research Report stated that under the current situation of low clinical efficiency, it continues to be optimistic about the growth of the clinical CRO market. As the qualification of clinical trial institutions changes from the certification system to the filing system, it is expected that more and more clinical trial institutions will participate in clinical trials, and the clinical CRO market is also expected to show a more diversified development.

Children's medicine may become a new trend

The just-concluded seventh census shows that there are about 253 million children aged 0-14 in my country, accounting for 17.95% of the total population, an increase of 1.35 percentage points compared with the previous sixth national census in 2010. With the liberalization of fertility policies such as "two children" and "three children", the proportion of children's population has rebounded, the number of children's population continues to increase, and the demand for children's medicines will also increase.

With the continuous growth of the market size and the continuous favorable policies, the children's medicine industry will usher in new development opportunities, and the trend seems to be imminent. But the reality is that as of September 2019, among the more than 6,000 pharmaceutical factories in my country, there are about 30 companies in the production department of children's drugs, and there are only more than 10 companies specializing in the production of children's drugs, and so far there are less than 10 companies. Family. According to statistics, the proportion of children's medicines in my country is less than 10% of the total amount of medicines, and more than 90% of them are not special medicines for children. In the absence of special medicines for children in clinical practice, children are often treated as miniature versions of adults to reduce the use of adult medicines, which poses a huge safety hazard.

For enterprises, the unmet needs in the reality gap are opportunities. In 2021, the review of children's medicines will be significantly accelerated, and 14 children's medicines have been approved for marketing so far. Among them, the new drug dartuximab beta (Dinutuximabbeta, dituximab) introduced by BeiGene was approved by the State Food and Drug Administration for the treatment of neuroblastoma, which can be used for more children with high-risk neuroblastoma. Bringing new treatment options to patients.

Epilogue

A crisis is a turning point, and a challenge is an opportunity. The annual report on the status of clinical trials of new drugs in 2020 released this time also confirms once again that China's biopharmaceutical industry has begun to move from boom to calm, from capital chasing to people-oriented. Perhaps under this fact of the data, it will bring new thinking and considerations to practitioners, allowing the local biopharmaceutical industry to move towards a healthier ecological model of development...

(Source: Yaozhi.com)