CDE releases new regulations for the development of anti-tumor drugs!

On November 19, the Center for Drug Evaluation (CDE) of the State Food and Drug Administration officially issued the "Guiding Principles for Clinical Research and Development of Anti-tumor Drugs Oriented by Clinical Value" (hereinafter referred to as the "Guiding Principles"), which will be implemented from the date of issuance
.
Focusing on the dimensions of research and development, clinical trial design, etc.
, the "Guiding Principles" proposes recommendations for the clinical research and development of anticancer drugs from the perspective of patient needs, with a view to guiding applicants to implement clinical value-oriented and patient-oriented research and development processes.
The core research and development concept provides an important reference for promoting the scientific and orderly development of anti-tumor drugs
.

 

The highest goal of new drug research and development is richer in connotation

 

In July of this year, the "Guiding Principles" first appeared in the form of a draft for comments and aroused the attention of the industry.
It was over-interpreted by some institutions as the conclusion that me-too new drugs have no future, and the clinical significance of oncology drugs and traditional chemotherapy are not significant.
At that time, the pharmaceutical sector, represented by CRO concept stocks, collectively "diving"
.
But in fact, the "Guiding Principles" are more about the further optimization and writing of the previous review standards , and put forward higher requirements for new drug research and development projects, preclinical and clinical programs
.

 

Regarding the selection of reference drugs, the "Guiding Principles" proposed that in a controlled trial, according to needs, positive reference drugs, placebos or Best Support Care (BSC) can be selected as controls
.
In an interventional clinical trial, without withdrawing the informed consent, the subjects must strictly follow the trial protocol to receive treatment, and cannot freely choose the treatment drugs/plans, and should try to provide subjects with extensive clinical practice The best treatment method/drug used should not be used to improve the success rate and efficiency of clinical trials.
The safety and/or effectiveness of the treatments are uncertain or have been replaced by better drugs
.

 

Control drugs are the basis for reflecting the clinical value of new drugs.
The "Guiding Principles" make it clear that when a non-optimal treatment is selected as a control, even if the clinical trial achieves the preset research goals, it cannot indicate that the trial drug can meet the actual needs of patients in the clinic.
Or it may not be possible to prove the value of the drug to the patient
.
Therefore, CDE emphasizes that when choosing a positive drug as a control, attention should be paid to whether the positive control drug reflects and represents the best treatment choice for the target patient in clinical practice; when planning to choose a placebo or BSC as a control drug, the adaptation should be determined There is indeed no standard treatment in the clinic; when there is BSC, BSC should be preferred as a control instead of a placebo
.

 

Whether the previous draft was overwhelmed by an official document, CDE has not changed in the "control drug of choice" requirements, which not only shows that regulators face of the current anti- cancer drug development clinical design demands for improvement of attitude, but also that It has improved the regulatory attitude towards domestic innovative drug research and development, and has raised the threshold for innovative drug research and development to a certain extent
.
However, it is worth noting that the "Guiding Principles" propose that the development of new drugs should provide patients with better (more effective, safer or more convenient, etc.
) treatment options as the highest goal, compared to the only "better" in the consultation draft.
The two characters give a richer connotation to innovative drugs
.

 

　　Accelerate the clearance of production capacity and guide the realization of "true innovation"

 

　　In recent years, China's innovative drug industry has developed vigorously
.
The data shows that in 2020, CDE has passed a total of 20 innovative drug marketing applications, and a total of 1062 category 1 innovative drug registration applications (597 varieties) have been accepted, an increase of 51.
71% over 2019
.
Among them, 1,008 IND applications (559 varieties) were accepted, an increase of 49.
78% over 2019; 54 NDA applications (38 varieties) were accepted, an increase of 100.
00% over 2019
.
In the distribution of indications for IND applications for Class 1 innovative chemical drugs approved in 2020, anti-tumor drugs account for more than 50%
.

 

　　However, parallel to the ascendant of local innovative drugs is the repetition of popular targets and tracks
.
Since Bristol-Myers Squibb’s Navulimab and Merck’s Pembrolizumab were approved for listing in China in 2018, domestic PD-1/L1 inhibitors have sprung up, and the domestic market has now gathered in Junshi Biotech.
Domestically produced PD-1 monoclonal antibodies from six pharmaceutical companies, Cinda Bio, Hengrui Pharmaceuticals, BeiGene, Kangfang Biological and Yuheng Biological, meanwhile, dozens of PD-1/L1 products are still on the market Applying or entering the clinical trial stage
.
On the same day when the "Guiding Principles" was issued, Kelun Pharmaceutical announced that the listing application for the PD-L1 monoclonal antibody tetlizumab injection developed by its holding subsidiary Kelun Botai has been accepted
.
In the medical insurance negotiations that just ended not long ago, a new round of price competition may pull down the full annual medication amount of PD-1 monoclonal antibody to the 30,000 yuan mark
.

 

　　After PD-1/L1 inhibitors, the CAR-T field has also become another "Red Sea" track
.
In June and September of this year, Fosun Kate’s Akilunza injection and WuXi Juno’s Regioranza injection were successively approved for marketing in China
.
It is reported that these two products have entered the Chinese market quickly through the establishment of joint ventures with domestic companies to carry out technology introduction and cooperation development
.
Judging from the regional distribution of the number of CAR-T cell therapy clinical trials registered on ClinicalTrials.
gov, China has surpassed Europe and the United States to become the country with the largest number of CAR-T cell therapy clinical trials.
It is expected to usher in a variety of CAR-T in the near future.
Cell therapy is on the market.
Nanjing’s legendary LCAR-B38M and Heyuan Bio’s CNCT19 cell injection are all “seed players” that have attracted much attention
.

 

　　The industry generally believes that with the formal implementation of the "Guiding Principles", in the short term, it will increase the difficulty for pharmaceutical companies to develop new drugs and combat "pseudo-innovation.
"
.
In the medium and long term, under the guidance of the "Guiding Principles", the production capacity of innovative drugs will be accelerated, leading enterprises to achieve "true innovation", and reducing homogenized competition.
Resources such as industry capital, technology, and clinical resources will be expected.
Concentrating on leading innovative companies, the concentration of the innovative drug research and development industry is expected to increase
.

 

　　As for the CXO companies that are currently on the cusp, some researchers pointed out that companies with a relatively large domestic business in the short-term may be affected.
CXO will continue to benefit from the upgrading of the domestic innovative drug industry, the order quality is expected to improve, and continue to share the results of the development of the global innovative drug industry at a deeper level.
The logic of the strong Hengqiang will continue to be verified
.

　　On November 19, the Center for Drug Evaluation (CDE) of the State Food and Drug Administration officially issued the "Guiding Principles for Clinical Research and Development of Anti-tumor Drugs Oriented by Clinical Value" (hereinafter referred to as the "Guiding Principles"), which will be implemented from the date of issuance
.
Focusing on the dimensions of research and development, clinical trial design, etc.
, the "Guiding Principles" proposes recommendations for the clinical research and development of anticancer drugs from the perspective of patient needs, with a view to guiding applicants to implement clinical value-oriented and patient-oriented research and development processes.
The core research and development concept provides an important reference for promoting the scientific and orderly development of anti-tumor drugs
.

 

　　The highest goal of new drug research and development is richer in connotation

 

　　In July of this year, the "Guiding Principles" first appeared in the form of a draft for comments and aroused the attention of the industry.
It was over-interpreted by some institutions as the conclusion that me-too new drugs have no future, and the clinical significance of oncology drugs and traditional chemotherapy are not significant.
At that time, the pharmaceutical sector, represented by CRO concept stocks, collectively "diving"
.
But in fact, the "Guiding Principles" are more about the further optimization and writing of the previous review standards , and put forward higher requirements for new drug research and development projects, preclinical and clinical programs
.

 

　　Regarding the selection of reference drugs, the "Guiding Principles" proposed that in a controlled trial, according to needs, positive reference drugs, placebos or Best Support Care (BSC) can be selected as controls
.
In an interventional clinical trial, without withdrawing the informed consent, the subjects must strictly follow the trial protocol to receive treatment, and cannot freely choose the treatment drugs/plans, and should try to provide subjects with extensive clinical practice The best treatment method/drug used should not be used to improve the success rate and efficiency of clinical trials.
The safety and/or effectiveness of the treatments are uncertain or have been replaced by better drugs
.

 

　　Control drugs are the basis for reflecting the clinical value of new drugs.
The "Guiding Principles" make it clear that when a non-optimal treatment is selected as a control, even if the clinical trial achieves the preset research goals, it cannot indicate that the trial drug can meet the actual needs of patients in the clinic.
Or it may not be possible to prove the value of the drug to the patient
.
Therefore, CDE emphasizes that when choosing a positive drug as a control, attention should be paid to whether the positive control drug reflects and represents the best treatment choice for the target patient in clinical practice; when planning to choose a placebo or BSC as a control drug, the adaptation should be determined There is indeed no standard treatment in the clinic; when there is BSC, BSC should be preferred as a control instead of a placebo
.

 

　　Whether the previous draft was overwhelmed by an official document, CDE has not changed in the "control drug of choice" requirements, which not only shows that regulators face of the current anti- cancer drug development clinical design demands for improvement of attitude, but also that It has improved the regulatory attitude towards domestic innovative drug research and development, and has raised the threshold for innovative drug research and development to a certain extent
.
However, it is worth noting that the "Guiding Principles" propose that the development of new drugs should provide patients with better (more effective, safer or more convenient, etc.
) treatment options as the highest goal, compared to the only "better" in the consultation draft.
The two characters give a richer connotation to innovative drugs
.

 

　　Accelerate the clearance of production capacity and guide the realization of "true innovation"

 

　　In recent years, China's innovative drug industry has developed vigorously
.
The data shows that in 2020, CDE has passed a total of 20 innovative drug marketing applications, and a total of 1062 category 1 innovative drug registration applications (597 varieties) have been accepted, an increase of 51.
71% over 2019
.
Among them, 1,008 IND applications (559 varieties) were accepted, an increase of 49.
78% over 2019; 54 NDA applications (38 varieties) were accepted, an increase of 100.
00% over 2019
.
In the distribution of indications for IND applications for Class 1 innovative chemical drugs approved in 2020, anti-tumor drugs account for more than 50%
.

 

　　However, parallel to the ascendant of local innovative drugs is the repetition of popular targets and tracks
.
Since Bristol-Myers Squibb’s Navulimab and Merck’s Pembrolizumab were approved for listing in China in 2018, domestic PD-1/L1 inhibitors have sprung up, and the domestic market has now gathered in Junshi Biotech.
Domestically produced PD-1 monoclonal antibodies from six pharmaceutical companies, Cinda Bio, Hengrui Pharmaceuticals, BeiGene, Kangfang Biological and Yuheng Biological, meanwhile, dozens of PD-1/L1 products are still on the market Applying or entering the clinical trial stage
.
On the same day when the "Guiding Principles" was issued, Kelun Pharmaceutical announced that the listing application for the PD-L1 monoclonal antibody tetlizumab injection developed by its holding subsidiary Kelun Botai has been accepted
.
In the medical insurance negotiations that just ended not long ago, a new round of price competition may pull down the full annual medication amount of PD-1 monoclonal antibody to the 30,000 yuan mark
.

 

　　After PD-1/L1 inhibitors, the CAR-T field has also become another "Red Sea" track
.
In June and September of this year, Fosun Kate’s Akilunza injection and WuXi Juno’s Regioranza injection were successively approved for marketing in China
.
It is reported that these two products have entered the Chinese market quickly through the establishment of joint ventures with domestic companies to carry out technology introduction and cooperation development
.
Judging from the regional distribution of the number of CAR-T cell therapy clinical trials registered on ClinicalTrials.
gov, China has surpassed Europe and the United States to become the country with the largest number of CAR-T cell therapy clinical trials.
It is expected to usher in a variety of CAR-T in the near future.
Cell therapy is on the market.
Nanjing’s legendary LCAR-B38M and Heyuan Bio’s CNCT19 cell injection are all “seed players” that have attracted much attention
.

 

　　The industry generally believes that with the formal implementation of the "Guiding Principles", in the short term, it will increase the difficulty for pharmaceutical companies to develop new drugs and combat "pseudo-innovation.
"
.
In the medium and long term, under the guidance of the "Guiding Principles", the production capacity of innovative drugs will be accelerated, leading enterprises to achieve "true innovation", and reducing homogenized competition.
Resources such as industry capital, technology, and clinical resources will be expected.
Concentrating on leading innovative companies, the concentration of the innovative drug research and development industry is expected to increase
.

 

　　As for the CXO companies that are currently on the cusp, some researchers pointed out that companies with a relatively large domestic business in the short-term may be affected.
CXO will continue to benefit from the upgrading of the domestic innovative drug industry, the order quality is expected to improve, and continue to share the results of the development of the global innovative drug industry at a deeper level.
The logic of the strong Hengqiang will continue to be verified
.