The number of declared Class 1 new drugs is not as good as the Hengrui family's Guangdong, why has fallen behind in the development of new drugs

Medical News, March 23.
Recently, the 2020 GDP performance was announced.
Guangdong Province continued to rank first with 11 trillion yuan, which is the same as the ranking in 2015 at the beginning of the 13th Five-Year Plan
.
Jiangsu Province ranked second with 1 billion yuan
.
However, Guangdong's drug R&D is not as bright as its GDP
.
If the products approved after the implementation of the new drug registration management measures are used as the criteria for judging R&D capabilities, after 2017, there will be only 3 new drugs in Class 1 approved from Guangdong Chemical Pharmaceuticals.
If classified according to the new registration, only 1 will be approved.
Batch
.
The three Guangdong companies that have been approved are not among the top 100 companies in China's pharmaceutical industry in 2019 .
Yichang Dongyang Sunshine has been approved for a Class 1 new drug emitavir phosphate capsules in 2020.
The address of the holder of the marketing license belongs to Hubei Province.
This approval has not yet been included in the approval scope of Guangdong Province .

Data source:
What are the top 100 pharmaceutical companies in Guangdong doing now?
According to the data of China's top 100 pharmaceutical industry in 2019, a total of 5 companies in Guangdong have entered the top 100 list, namely Guangzhou Pharmaceutical, United Laboratories, Dongyang Pharmaceutical, Livzon Pharmaceutical and Xinlitai .
The five chemical drugs approved under the new registration classification in recent years are basically generic drugs .
Livzon's ilaprazole sodium for injection was approved in 2017 in the old category 2.
It is one of the few improved and innovative drugs approved by Guangdong head pharmaceutical companies .

Data source: Xianda Pharmaceutical Sea Database If the approval status is not "on the hero", what is the status of Guangdong's Class 1 new chemical drug application? Maybe we can see the clues from it .
First of all, there are fewer approvals for innovative drugs, directly due to fewer declarations






.
Taking Guangzhou Pharmaceutical Group as an example, Guangzhou Pharmaceutical has only declared a product of cefazimidine sodium for injection, which was approved for clinical use in 2017.
As of 2020, the drug’s research and development progress shown in the CDE is to start the cefazimidine sodium for injection.
Clinical research on safety, tolerability and pharmacokinetics of single-dose administration
.
Secondly, the relatively high risk of research and development of innovative drugs is also an unavoidable problem
.
Take Dongyangguang as an example.
As the company with the most declarations of Class 1 chemical drugs in Guangdong Province, currently only one drug for hepatitis C, imitavir, is on the market
.
According to the research progress, the next products that may be marketed are the hepatitis C drugs vorarivir and pyroglutamate rongpagliflozin in clinical phase III
.
From the perspective of progress, the rest of the drugs will have to wait at least 3 years to see whether they can be marketed
.
In addition, it is worth noting that some clinical approvals that were not launched in 2017, and phase I of clinical trials were launched in 2018.
If there is no further progress, it is very likely that the project will not continue
.
According to this standard evaluation, Dongyang Sunshine may have cut down 9 new drug projects
.
If the pre-clinical investment cost of one project is 25 million yuan and the phase I clinical investment cost is 35 million yuan, 6 projects will enter the first phase and 3 pre-clinical
.
It is estimated that Dongyang Sunshine will invest nearly 300 million yuan in research and development projects.
This data does not include the input of supporting APIs, preparations and clinical human resources for the five-year research and development of new drugs
.

　　 Data source: Xianda Yaohai Database.
The failure case in 2021 is also Biotek
.
In February 2021, Biotech announced the termination of the BAT8001 (recombinant humanized anti-HER2 monoclonal antibody-maytansine conjugate for injection, hereinafter referred to as "BAT8001") clinical trial
.
In March 2021, Biotech announced that it developed BAT8003 (recombinant humanized anti-Trop2 monoclonal antibody-maytansine conjugate for injection, hereinafter referred to as "BAT8003") and BAT1306 (recombinant human origin).
Chemical anti-PD-1 monoclonal antibody injection (hereinafter referred to as "BAT1306") is in the clinical research stage
.
After careful consideration of the risk of subsequent development of the drug, Biotech decided to terminate the clinical trial of the project
.
The phase III clinical study of BAT8001 for HER2-positive breast cancer is a multi-center, randomized, open, positive-controlled, and superior phase III clinical study in China
.
As of 2020, Biotech has invested 226 million yuan in research and development in this project
.
BAT8003 is an innovative drug independently developed by Biotech.
It is an ADC drug targeting Trop2.
A recombinant humanized anti-Trop2 monoclonal antibody modified by glycosylation is covalently linked to Batansine through site-directed coupling technology.
Into
.
As of December 31, 2020, the BAT8003 project has invested a total of 61.
565 million yuan in research and development
.
BAT1306 is a monoclonal antibody against immune suppression checkpoint PD-1 developed by the company.
The single-drug indication is EBV-related gastric cancer.
At present, BAT1306 combined with XELOX first-line treatment of EBV-related gastric cancer clinical trials and BAT8001 combined with BAT1306 second-line treatment of HER2-positive advanced stage Clinical trials of solid tumors
.
As of December 31, 2020, the BAT1306 project has invested a total of RMB 51,974,500 in research and development
.
Third, the development cycle of new drugs is long and the uncertainty is high
.
The research and development cycle of new drugs is long.
According to the current domestic regulations, pre-clinical research information can only be obtained from the literature and conference reports
.
After the new drug is approved for clinical use, ideally, it will take 1 to 2 years for both phase I and phase II, and 2-3 years for phase III.

.
For example, the biological product AK101 injection of Zhongshan Kangfang was approved for clinical use in September 2017, but the Phase III clinical study has not been officially launched in 2020
.

Source: The time from the release of the new registration classification of CDE chemical drugs to March 2021 is too short to support the product to complete the entire clinical study of Phase I, Phase II to Phase III .
Except for new drugs that meet the conditional listing criteria and complete Phase II clinical trials, other new drugs must complete Phase III clinical studies before they can be declared .
After the release of the new registration classification of chemical drugs, Guangdong has filed a total of five applications for the marketing of new category 1 drugs.
Among them, the benzenemod cream and emitavir phosphate capsules mentioned above have been approved for marketing .
Pianprizumab injection is the first and only PD-1 injection of a Guangdong enterprise to apply for listing, and the date of application for listing is 2020 .
Compared with 2018, Junshi Biologics PD-1 Teriprolizumab Injection was conditionally approved by the State Food and Drug Administration, becoming the first domestically produced PD-1 product approved for marketing, a full 2 ​​years later .
The number of products declared for listing of Class 1 new drugs in one province in Guangdong is not as good as the number declared by Hengrui's family .

　　Why is Guangdong's R&D so late to produce results?
Guangdong Province is the province with the largest domestic drug sales market, and it has always been a province where all pharmaceutical companies have to deploy their marketing .
However, in recent years, Guangdong's drug research and development institutes have shown far less transcripts than Jiangsu .
In the Shanghai and Shenzhen stock markets, the market value of chemical pharmaceuticals ranked (from high to low).
According to the snowball data on March 16, 2021, Jiangsu Hengrui ranked first with 473.
7 billion yuan, and Xinlitai and Livzon Group in Guangdong Province ranked first with 473.
7 billion.
37.
7 billion and 33.
5 billion ranked 7th and 10th respectively .
In the field of biological products, there is no listed company in Guangdong whose market value can squeeze into the top 10 .
Hong Kong stocks Kangfang Biotech's market value of 38 billion has the potential to squeeze into the top 10　 　










.
The possible reasons why Guangdong Province can't compete with Jiangsu Province are as follows: First, Guangdong Province is just a province in battle.
Jiangsu Province and Shanghai, Zhejiang and other provinces have cooperated closely and have formed industrial synergies
.
After many years of accumulation of API exports in Zhejiang Province, individual API products already have cost advantages in the world
.
Most of the enterprises in Guangdong Province started from domestic circulation.
Before the reform of pharmaceutical circulation, they had already lived very well with policy dividends and did not actively deploy APIs
.
Provinces near Guangdong, such as Fujian, have not developed the import and export business of APIs like Zhejiang, and the entire Pearl River Delta has not established a good API foundation
.
The dilemma of APIs is also reflected in the CRO organization, and the number of CROs in Guangdong is not as large as that in the Yangtze River Delta
.
Secondly, Guangdong enterprises prefer to "make tricks"
.
After centralized procurement, raw material preparation integrated enterprises with competitive advantages in cost management will be able to gain access to the market
.
Guangdong enterprises that do not have the advantage of raw materials are more clever to win in the competition.
For example , the higher bidding price of the garden medicine industry in the fourth centralized procurement , winning a higher market scale has caused heated discussions in the industry
.
This is actually the culture of Guangdong pharmaceutical companies—policy opportunistic companies, where the policy orientation is laid out, and they prefer to use the rules to obtain higher profits after reading the rules
.
This means that the faster the short-term return on which type of project is, the more enterprises in Guangdong are willing to invest, and projects with slow returns on heavy assets are often not favored in Guangdong
.
Third, the government's investment
.
In the past two years, Guangzhou and Shenzhen finally started the war of robbing people and projects in biomedicine
.
However, the more difficult it is to change the production location of biological products in the later stage of research and development, which means that Guangdong Province has missed the best development stage of PD-1 and CAR-T.
Although BeiGene has a production base in Guangzhou, it is not its headquarters.
The core of R&D is not in Guangzhou either
.
This means that the bright spot performance of biological products in the industry in the next three years has nothing to do with Guangdong.

.
ADC, double antibodies, and nucleic acid drugs may still have opportunities to compete.
Among them, Zhongshan Kangfang may have a breakthrough in the field of double antibodies
.
Fourth, the lack of talents
.
There are not many pharmaceutical-related R&D universities in Guangdong, and the strongest may be Sun Yat-Sen University
.
The students graduating from China Pharmaceutical University each year usually give priority to the Yangtze River Delta, and not many talents flow to the Pearl River Delta
.
Central South University (Xiangya Medical College), the nearest university in Guangdong, and Wuhan, Hubei, have no close cooperation and manpower drainage
.
In terms of high-tech talents, the salary of Guangdong R&D personnel has no advantage compared with that of the Yangtze River Delta.
This is mainly because the existing pharmaceutical companies in Guangdong have average operating income levels, and most of Guangdong’s bosses are very particular about annual profit performance.
The profit volume is used to calculate the salary of the R&D team
.
In addition, most of the bosses in Guangdong are not in R&D but in marketing.
They often use marketing management methods to manage R&D teams.
Marketing teams often pay attention to the wolf pack effect and are more willing to reward wolves, but R&D is more focused on cooperation.
Every link must meet the standards, and a harmonious and win-win atmosphere is necessary.
If the boss does not take good care of the key personnel in the key core links, it will be difficult to produce results
.
Therefore, the enterprises that may produce results in Guangdong can only hope that the big cows with technology and market sense will come back to start their businesses
.