When Me-too becomes We-too, how should China take the road of innovative drugs?

After the trough caused by the drug registration verification storm in 2006, the domestic innovative drug declarations began to grow slowly from 2009; after the implementation of the new policy of Biopharmaceuticals in 2015, innovative drug research and development entered an outbreak period, and the number of new drug declarations reached a record each year New high, by 2020, only 909 chemical innovation drug (class 1 new drugs) registration application acceptance numbers, and 835 approved acceptance numbers (on average, there are 2 acceptance numbers for a variety, which is equivalent to more than 400 new drugs).
The number of innovative chemical drugs approved for clinical and production annually may be more than that of the United States.

Trends in the registration and application of China's chemical innovative drugs (category 1) (according to the acceptance number)

Image source: Yaozhi Consulting

What is an innovative drug? It is not a low-tech generic drug, let alone Chinese cabbage sold all over the street, but why are there so many declarations? Is it true that China's pharmaceutical innovation has entered the world-class level? Wait a minute, we can't just look at the quantity, but also analyze the quality.

Innovative drugs refer to "innovative drugs that have not been marketed at home or abroad (new structure)", which is what we commonly call Class 1 new drugs.

The "improved new drug" called 505b(2) in the United States is not among the innovative drugs discussed in this article.

Both are innovative drugs, but there are also differences between them.

Among them, the highest is "First in class"-that is, the original innovative drug, which requires not only new molecular entities, but also new mechanisms (new targets) or new indications.
Have advantages that existing drugs do not have.

We often hear that "it takes 10 years to develop a new drug and US$1 billion (now it needs US$2 billion).

” This refers to this type of new drug.
The difficulty is obvious.
China has been recognized internationally for decades.
Innovative drugs are only a few drugs such as artemisinin and dimercaptosuccinic acid.

Does China currently develop "First in class"?

This kind of medicine is not only difficult, but also more risky, because the essence of "First in class" is to take a path that has not been walked/passed by predecessors, but the benefits are also great.

There are some powerful large enterprises and innovative companies in China.
The team is also conducting research and development, but the road is long and long, and it needs to be searched up and down.

If it is said that "First in class" takes a path that has not been walked/passed by the predecessors.

The Me-too medicine means that after seeing others get it through, and then developing (modifying) a similar medicine to go the same way, the risk and difficulty are greatly reduced.

If you don’t make modifications and are exactly the same, it’s not a Me-too drug, but a generic drug (ANDA), and you need to wait until the patent protection period expires before you can imitate it.

It is necessary to walk the way of others, but also to avoid patents, so Me-too medicine came into being.

This operation is even more extreme in China.
The common method is that the mechanism of action and indications remain unchanged, and only a slight change to the structure of the compound is required to become a compound that can circumvent patents.

Diagram of the relationship between drug development type and investment/risk

Image source: Li Tianquan Yaozhi Consulting

We have also heard of a class of drugs called Me-better, which is an individual drug in Me-too.

After modification, its clinical effect is significantly better than the first-in-class drug "First in class".
In China, although Me-better drugs are everywhere, they are actually very few, because the real Me-better needs to rely on clinical trial data to speak, if it is not head-to-head with "First in class" The comparative test is not qualified to call oneself a Me-better.

What's more, the clinical effect of some Me-too drugs is actually not as good as the drugs before the transformation, we call them "Me-worse".

Although developers never admit that their drugs are "Me-worse", many innovative drugs in China actually fall into this category.

For word games, Chinese people have always enjoyed it, not only for Chinese characters, but also for English words.
Recently, a word has appeared, and the image is appropriate.
It can be called a hit! It is said that the new drug developed in China is no longer Me- Too (you have and I have), but We-too (you have, we have), that is, whenever a brand-new drug comes out, we will have a bunch of companies to follow suit, until the Me-too drug is made We-too drugs, this is the beginning of the article saying that more than 400 new drugs have been approved for clinical or production in 2020, and finally successfully upgraded China's drug R&D from low-level repeated research to high-level repeated research.
I once said that no matter how good the track is, it will become crowded in China.
Maybe We-too medicine is the best footnote.

This is not only true of chemical drugs, but also biological drugs known as cutting-edge technologies.
For example, similar innovative drugs targeting PD-1 have been registered and declared by more than 60 manufacturers.
Now that the track has become so crowded, why do everyone still enjoy it?

National drug purchases have brought the price of generic drugs to a trough, but for pharmaceutical companies, there is no way out without R&D.
Generic drugs are suppressed, and investors and local governments have favored innovative drugs.
The vast majority of Chinese companies have neither technical capabilities nor financial strength to be "First in Class".
Me-too medicine has become an inevitable choice for many pharmaceutical companies in desperation, not to mention that they have some dreams when setting up the project.
, What if you make a better Me-better?

Under the past drug registration system, original innovative drugs were launched in China 5 to 8 years later than Europe and the United States on average, and this time difference is the best bonus basis for Me-too (including Me-worse).
However, with the changes in drug registration and supervision in the past few years, after innovative drugs are gradually launched in China, Me-too drugs will become more and more difficult to follow.
Although the road to technology is easy, the road to market is difficult, so we will listen.
Some news that seemed to be a joke: "Because the XX innovative drug was launched, the company's valuation/market value has fallen", because the originally anticipated new drug has hit a bloodshed in the face of the cruel market.

In order to change the status quo in China, from a national level: First, we must strengthen basic research.
Many innovative drugs, such as Viagra, were born behind a Nobel Prize invention.
Without basic research, there would be no new mechanisms and new targets.
The discovery, without these discoveries, how can we talk about a truly innovative medicine.
We can’t expect Europe and the United States to do basic research.
China will do “First in class” research and development.
It is not sustainable to pick what is available.
Of course, for a single company, it can keep up with the forefront of life sciences in the world and look for opportunities.
Tracking the latest literature is an effective method.
one.

The second is to optimize the market environment for innovative drugs.
The invisible hand of the market is the real baton!

Although the basic research of biomedicine in China is relatively weak, it is not without it.
Even international results can be used by me.
So why are few people in China willing to be "First in class"?

In addition to technical issues, there is also a more important issue of the market-China's drug consumer market (the term is improper, but the drug is actually a commodity) is not friendly to innovative drugs:

First, it is difficult to enter medical insurance.
In the past, only when the medical insurance catalogue was adjusted every five years could there be a chance to enter the medical insurance.
Of course, with the dynamic adjustment of the medical insurance catalog, innovative drugs can be negotiated into the medical insurance, and some of them have now been resolved.
From 2016 to 2020, there were a total of 194 innovative drugs on the market in my country, and 119 of them have been included in the National Medical Insurance Catalogue for 2020.

The second is that it is difficult to enter the hospital, and it is impossible to enter the hospital with medical insurance.
According to statistics from 1,420 sample hospitals of the Chinese Pharmaceutical Association, as of the end of 2019, less than 20% of innovative oncology drugs included in medical insurance in 2018 were successfully admitted to hospitals.

Third, it is difficult for high-priced drugs to gain a foothold in the Chinese market.
One billion US dollars of research and development costs require high-priced drug prices.
Innovative drugs in the United States are purely market-oriented.
Original new drugs are basically accompanied by high prices.
Even high-priced drugs appear from time to time.
Actimmune, a drug for the treatment of two rare diseases, osteopetrosis and chronic granulomatosis, costs as much as a month.
52322 US dollars (each needle price is 4360 US dollars).
This is unthinkable in China.
There are neither patients nor medical insurance willing to pay for it (national medical insurance only guarantees the basics, while commercial medical insurance is too weak), and they may even scold the bosses of pharmaceutical companies for having no conscience.
Therefore, in the price negotiation of innovative drugs, soul bargaining is often encountered, and the price of entering medical insurance is the price cut.

Finally, various support policies for orphan drugs (orphan drugs) need to be introduced as soon as possible.
my country's emphasis on orphan drugs is still verbal, and there is no clear policy support.
Therefore, large varieties of innovative drugs are crowded together, and no one cares about orphan drugs.

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