Embarrassing 1.2 new Chinese medicines

The listing of icariin soft capsules has made the industry begin to re-examine the 1.
2 class of new traditional Chinese medicines
.

New drugs in category 1.
2 of traditional Chinese medicine, that is, extracts and their preparations extracted from a single plant, animal, mineral, etc.
, this definition makes it seem that the development of new drugs can be carried out according to both traditional Chinese medicine and chemical drugs
.

Questioned by the outside world, the number of approvals is small, and the 1.
2 categories of new drugs with less R&D investment by the industry are the "nails" of new traditional Chinese medicines that are difficult to develop and approve? Or is it a "dark horse" for innovative Chinese medicine to go to the world in the future?

01

1.
2 What do new Chinese medicines look like?

China's drug registration classification and technical requirements have undergone seven revisions
.

Compared with the 2007 version of the "Administrative Measures for Drug Registration", the current classification of traditional Chinese medicine registration has been greatly adjusted
.

According to the article "Analysis of Class 1.
2 of Innovative Traditional Chinese Medicine Drugs and Thoughts on Quality Control of Extracts" published by Zhao Xiaoxia of the Center for Drug Evaluation of the State Drug Administration on December 31, 2020 in China Journal of Traditional Chinese Medicine, the registration of new Chinese medicines The adjustment of classification reflects two important directions: one is to emphasize the clinical value orientation and encourage innovative research and development of traditional Chinese medicine; the other is to no longer only use the material basis as the basis for classification
.

The current "Measures for the Administration of Drug Registration" (2020 version) dilutes the content requirements of "active ingredients" and "effective parts" in the original registration classification management, but emphasizes the clinical value orientation, and must be determined after systematic research.
An extract of a group of ingredients, rather than a medicinal substance prepared only by traditional extraction methods
.

According to the above paper, Professor Li Lianda of the Chinese Academy of Chinese Medical Sciences once proposed, "The research of traditional Chinese medicine is from the clinic, to the laboratory, and back to the clinic; while modern Chinese medicine refers to the theoretical guidance of traditional medicine or modern medicine, through the use of modern medicine.
For new drugs developed by scientific theories, methods and means, more emphasis is placed on development and innovation, and more emphasis is placed on synchronizing development with the international level, and emphasis should be placed on preclinical basic research
.

In addition, according to the interview with the manager of E medicine, whether the active ingredients have undergone chemical synthesis or structural transformation is considered by the industry as the core key factor to distinguish 1.
2 new traditional Chinese medicine drugs from chemical drugs
.

Not long ago, the State Drug Administration issued an announcement officially approving the 1.
2-category new traditional Chinese medicine icariin soft capsules (formerly known as Akela) of Beijing Shennuoji Pharmaceutical Technology Co.
, Ltd.
, Icaritin) was approved for listing with conditions
.

The core component of the medicine is icariin, an effective monomer compound extracted and purified from the traditional Chinese medicinal material Epimedium, for the treatment of advanced liver cancer
.

The Guangjincao total flavonoid capsules of Renfu Medicine, which is in the stage of approval for listing, are also new drugs in category 1.
2 of traditional Chinese medicine
.

The Alisma jiangzhi capsule of Kangyuan Pharmaceutical Co.
, Ltd.
is also a category 1.
2 innovative traditional Chinese medicine drug, which is still in the clinical trial stage
.

02

3 major difficulties in research and development

"Usually, the development cost of new Chinese medicine 1.
2 drugs is high, and the difficulty of pharmaceutical research and development is higher than that of Chinese medicine 1.
1 new drugs
.

According to NMPA data, from 2017 to 2022, a total of 21 new Chinese medicines were approved, of which 12 were approved in 2021, the year with the largest number of approvals in the past five years
.

However, it can also be seen from the data that it is difficult and relatively scarce to declare new drugs in category 1.
2 of traditional Chinese medicine
.

On the whole, in terms of research and development, the difficulty of category 1.
2 is mainly reflected in the following three aspects:

First, a certain type of Chinese herbal medicine is effective in treating a certain disease, but which ingredient or type of ingredient plays a major role requires more comparison and research, which is much more difficult than developing a Chinese herbal compound;

Second, after a certain ingredient is found to play a major role, what method is used to extract the effective ingredient for treating a certain disease and purify it to meet the requirements.
The technical requirements in this area are also very high
.
To obtain monomers or effective parts from medicinal materials for 1.
2 new drugs of traditional Chinese medicine, the process research requires not only modern traditional Chinese medicine extraction technology, but also purification technologies such as separation and purification, and higher requirements for purification and purification software and hardware;

Third, in the clinical research of new Chinese medicines of Category 1.
2, in addition to the evaluation system of the efficacy of traditional Chinese medicine, the evaluation system of the efficacy of Western medicine is also indispensable
.

"The research and development process requires both the concept of traditional Chinese medicine and the technology of chemical medicine.
The process is not easy.
At present, there are not many domestic enterprises that make 1.
2 new traditional Chinese medicine drugs
.
" Wang Tingchun said
.

In Wang Tingchun's view, from the perspective of the past development process of traditional Chinese medicine, there have been cases such as adverse reactions of traditional Chinese medicine injections, which have been criticized in many places.
pure", and due to insufficient clinical trials in certain historical periods
.
Even if there are some effective traditional Chinese medicine injections, there will be more or less the problem of general curative effect or more adverse reactions
.
In this context, it is even more necessary for new Chinese medicines such as category 1.
2 with "clear ingredients, high purity of active ingredients and few impurities, and the completion of clinical phase III according to specifications" to appear
.

In the early stage of basic research, clinical trials and approval, category 1.
2 innovative drugs are also unique from chemical drugs and other types of traditional Chinese medicine
.

In terms of basic research, 1.
2 new Chinese medicines have discovered their special treatment mechanisms through the research of Chinese herbal medicines, so as to further extract their core active ingredients, and the directionality is more clear
.

In the clinical trial stage, the indicators of the efficacy of the disease, the standard of chemical medicine and traditional Chinese medicine are consistent, and in the treatment of a certain TCM syndrome, traditional Chinese medicine needs to add an evaluation system for TCM syndromes in addition to the disease evaluation system
.
Therefore, in the evaluation system, there is one more content than chemical drugs
.

In terms of review and approval, there will be more high standards and strict requirements for purified effective extract drugs
.

A professor of Chinese pharmacy told the E-pharmaceutical manager that although Chinese medicine 1.
2 innovative drugs are different from chemical drugs in theoretical basis, in fact, in terms of research and development technology, the relevant requirements are basically the same
.

"Although the traditional Chinese medicine 1.
1 category is more in line with the traditional Chinese medicine concept than the 1.
2 category, the risk is relatively small, and the number of reviewers is also more
.
However, the traditional Chinese medicine category 1.
2 innovative drugs still have their own unique significance
.
Compared with the 'big compound formula' 'Traditional Chinese medicine, 1.
2 new Chinese medicines mark the development of new Chinese medicines in the direction of clear ingredients, standardized process, and safety
.
" Wang Tingchun believes that 1.
2 Chinese medicines have the most opportunity to "go overseas" and are more likely to be favored by the US FDA.
, the world's innovative traditional Chinese medicine
.

03

Commercial selection of western medicine and traditional Chinese medicine?

After the approval of the 1.
2 new Chinese medicine drugs, whether to follow the "traditional Chinese medicine road" or the "western medicine road" when commercializing, how to better obtain clinical recognition of modern Chinese medicine innovative drugs is also a challenge
.

A person in charge of a pharmaceutical company engaged in the marketing of traditional Chinese medicines told the manager of E-pharmaceuticals that the promotion model of category 1.
2 traditional Chinese medicines is more inclined to the mode of chemical medicines, and it is easier to be recognized in Western medicine
.
"Class 1.
2 new traditional Chinese medicines are approved in accordance with the current drug registration management measures.
The drugs have been verified through strict clinical trials, and the indications in the drug inserts can be understood by both Western medicine and traditional Chinese medicine
.
"

Niu Ben, an independent observer in the pharmaceutical industry, said in an interview with the E-pharmaceutical manager that in the clinical promotion strategy, whether to choose Chinese medicine promotion or Western medicine promotion is a "dilemma" that enterprises will encounter in commercial operation: on the one hand, The mainstream diagnosis and treatment system with a large number of patients and mainly Western medicine, on the other hand, is the treatment of traditional Chinese medicine with a relatively small number of patients
.

Another embarrassment is that Chinese medicine prescribing medicines emphasizes "the ruler, ministers and assistants", which needs to conform to the traditional theory of Chinese medicine.
It remains to be seen whether a single drug can be recognized by Chinese medicine doctors
.

Not only that, the state has restrictions on Western medicine physicians prescribing traditional Chinese medicine, which must be trained and assessed
.
In June 2019, the National Health and Medical Commission issued the "Notice on Printing and Distributing the First Batch of National Key Monitoring and Rational Drug Lists (Chemical Drugs and Biological Products)", restricting the qualifications of physicians who prescribe Chinese medicine, and have not participated in Chinese medicine related Systematic study or training of Western medicine will not be able to easily prescribe Chinese medicine
.

However, the number of practicing (assistant) physicians in the TCM category only accounts for 15.
9% of the entire group of practicing physicians
.

In this regard, Niu Ben put forward two suggestions.
First, use the cultural concept of the development of traditional Chinese medicine, promote the treatment technology dominated by western medicine, and compare the clinical efficacy with more similar products;

Secondly, the 1.
2 new traditional Chinese medicine drugs are benchmarked with mainstream drugs and biological drug products to highlight the advantages of the 1.
2 new drugs, and accurately locate them in specific treatment stages
.

Du Chen, a well-known pharmaceutical enterprise strategy expert and president of the Beijing Research Institute of E-pharmaceutical managers, suggested that in the process of market promotion, do not exaggerate the promotion of drugs, seek truth from facts, and do academic promotion, and there must be clinical evidence.
The patient explained clearly, that is, what can be treated and what the side effects are, and I believe that a good clinical effect is the best marketing measure
.

Taking the clinical promotion of the marketed icariin soft capsules as an example, Niu Ben said that from the perspective of the number of patients and the mainstream direction of diagnosis and treatment, if the academic promotion starts from the TCM department, the number of liver tumor patients in TCM hospitals is relatively small.
The sales volume will not be too large; and the current top tertiary hospitals, whether before or after surgery, the mainstream treatment of liver cancer is still dominated by chemical drugs and biological drugs, and there are many mainstream products
.
Not only that, whether drugs can be placed in hospitals is also affected by the reform of DRG/DIP payment methods.
Under the guidance concept of "good and cheap, medical insurance payment recognition" in hospitals, the 1.
2 class innovative drugs of traditional Chinese medicine have not yet entered the medical insurance premise.
, Whether the entrance channel can be successfully opened up remains to be considered
.
If you encounter difficulties in entering the hospital, you can also consider going to the out-of-hospital market for promotion
.

It is reported that Hangzhou Zhongmei Huadong Pharmaceutical Co.
, Ltd.
, a wholly-owned subsidiary of Huadong Medicine Co.
, Ltd.
, has obtained the exclusive marketing right of "Icariin Soft Capsule" in 27 provinces in mainland China
.

Niu Ben pointed out, "Including the popularized icariin soft capsules into the consensus of doctors on the treatment of advanced liver cancer, and promoting it from the treatment theory of Western medicine, is more tenable
.
However, if the drug wants to become a mainstream drug in the short term , it is difficult to obtain the recognition of a large number of doctors and patients
.
After listing, a large amount of real-world data is still needed to explain, and it takes time to take the road of market promotion .

”

Since icariin soft capsules are marketed with conditions, Duchen suggested to actively promote the fourth-phase clinical trials of this drug after the listing, and to consolidate the basic skills in terms of data, evidence-based medicine and academic promotion to doctors
.
"In terms of academic promotion, in view of the large number of samples required for clinical data in the fourth phase, Chinese and Western medicine can be carried out simultaneously, but compared with the two, it will be easier to follow the path of Western medicine
.
" In addition, drugs can be promoted to be included in medical insurance in the later stage
.