What's missing from the development of a new drug in China's first in class?

By the end of 2020, the national team was playing, and there was another uproar outside the industry.
PD-1 single resistance continues to dive, constantly refreshing the price awareness of innovative drugs.
O and K drugs have not been shortlisted and want to be associated with MNC maintaining the global price system.
local pharmaceutical companies have no such scruples.
is only the price today, and if you compare it with the industry's expectations a few years ago, the difference is certainly a lot of shush.
industry is probably asking: "China's innovative drugs, in the end how to do down?" When fast follow-up has been in the process of internal roll-up for more than a decade, the pace at which China's innovative drugs are following the global frontier is changing.
back to the beginning of this century, Imatini was listed, domestic generic drugs after six years of multi-party research and development.
the end of 2014, O drug has just been approved in the United States, a number of domestic PD-1 monoantial clinical research has been hot.
, the time difference between domestic and foreign research has narrowed further.
such a fast follow strategy, in the past in the country has indeed achieved a number of me-too, me better (also including me worse) varieties and related enterprises.
It's only today, when the follow-up point for domestic fast follow-up has quietly moved from the market to Phase III, Phase II, and even preclinical stages, the number of competitors has expanded from a few to a dozen, or even dozens.
To give an example, with Claudin 18.2 target point, the world's only Astellas Pharma in Phase III, but China has appeared has been nearly 20 local pharmaceutical companies in the study, including Maya, Tian Guangxi, Genesis, etc. have entered Phase I, in the research project category in addition to single resistance, there are dual resistance, ADC and even CAR-T.
similar conditions are seen on the PD-L1/TGF-β, Trop 2-ADC circuits.
18.2 project leading the research and development phase Source: Pharmaceutical Rubik's Cube NextPharma Database The fast follow-up of local innovative pharmaceutical companies is experiencing "internal roll-up" in the most fashionable words of the day.
PD-1 single resistance today, it is very likely that other targets fast follow tomorrow.
if inferred by application potential, even the high probability is not as good as PD-1.
these trends, what is the way out of local innovative medicine? For now, first in class is the possible answer.
First in Class Made in China: Nobody did it, or didn't do it well? The industry's definition of first in class usually refers to the development of innovative drugs for the world's first target or mechanism.
this as a standard, the well-known Chinese-made "heavy bomb" Ektini, Compaxip, Apatini and other varieties following mature targets, obviously not called first in class.
so the problem comes, is there really no intention of Chinese pharmaceutical companies to do first in class? In fact, it may not be so! In terms of target and mechanism innovation alone, the first lysovirus drug, Ankery, which was first marketed in China more than a decade ago, and today's students, including the 971 approved in recent years, are considered first in class.
Even if the research and development strategy of the domestic innovative pharmaceutical industry in the past ten years has shifted the overall focus to fast follow, there is no shortage of new targets or mechanisms in the domestic research varieties of drugs, whether it is derived from the new discovery of basic scientific research, or from the purification of the active ingredients of natural products.
the real problem is that the vast majority of these new mechanism drugs, which were born in Chinese institutions, did not enter the clinic, or stagnated shortly after entering the clinic, and over time beed mattered to the public.
are occasionally listed and have not been widely recognized on the clinical side, nor have they been widely recognized at home and abroad.
so far, it seems that no Chinese companies have developed a new first in class drug by other companies at home and abroad fast follow.
From this, it can be inferred that the reason for the failure of China's first in class, the drug is not recognized as a mere appearance, the real essence is that the drug behind the new target or mechanism has not been widely recognized by domestic and foreign industry and academia.
: China's innovative drug research and development of the shortest plate drug target mechanism recognition is not high, in the final analysis is the lack of relevant research level.
the level of biomedicine research in China so weak? That's probably a score.
drug research and development can often be divided into three pieces: basic research, translational research and clinical research.
basic scientific research explores the discovery of new signaling path, genetic genes and other molecular mechanisms by conducting relevant research on various types of cells and animal models.
clinical studies are conducted in humans to verify the safety and effectiveness of treatment methods.
the general public understanding, there is often a large gap between basic research and clinical research, and the bridge between the two is transformational research.
On the one hand, whether the new mechanisms found by basic scientific research from the model are the same as those found in the human body, these often need to be further confirmed by some scarce models closer to the human body (e.g. primary cells, tissue samples, humanized mice, etc.), and in accordance with industry standards for repeated verification, dose exploration and other work, the relevant findings are reliable, and whether the disease is related and so on.
On the other hand, some accidental findings of clinical studies, such as the effectiveness of special drug combinations and the sensitivity of specific populations, can identify clear molecular-level mechanisms and develop interventions based on relevant findings, also require a return to the field of translational medicine for more detailed research.
scientific research, China has made great progress in the past ten years.
four cnS Chinese mainland published in 2005, 100 in 2018 and more than 150 in 2020 (including nearly 50 new Crown CNS papers).
in many sub-sectors, Chinese scientists, especially young scientists in the post-70s and post-80s age groups, have begun to emerge, and world-class leading basic research results are emerging frequently, and the future is worth looking forward to.
clinical research, China's top results are relatively less frequent than basic research.
But given Chinese mainland's large patient population and the strong resource mobilization capabilities of a number of clinical top PIis, there are many obvious advantages of clinical research in China, such as group speed, and they are equally important globally.
In contrast, China's transformational research is significantly weak, the reasons behind this include long-term fragmentation of the foundation and clinical, the lack of industry concept and recognition, the lack of leaders and executive teams and many other historical factors, although in recent years also began to improve, but still from the international leading level of a large gap.
the first in class of the missing transformation study: What is the state of the innovative drug of the missing transformation research that is rooted in the long and the long-term of the wood? Professor Attila A. Seyhan, from Brown University, published a review in 2019 that suggests that the concept of valley of death exists in basic and clinical research, and that there are many problems, including the repeatability and clinical relevance of research results, all of which need to be addressed through translational research.
to look at some of the domestic transformational research is not deep enough, or even missing first in class, often encountered situations include: said to be for an adaptive global first innovation mechanism, but the target has not been clear; A number of exploratory studies have been carried out on the relevant mechanisms, but the evidence is scattered and insufficient, or the evidence is not sufficient, the results of the drug ability experiment are ambiguous, plausible, other institutions or CROs are difficult to repeat, the credibility of important experimental data is insufficient, peer/client/regulatory approval is not high, the toxicological dosage, the frequency of drug treatment is insufficient, the clinical programme design is difficult, the abnormal data of clinical trials can not be explained, do not know how to intervene and improve.
don't say first in class, the lack of conversion research, even fast follow may not do well.
The followers of new targets in China, in many cases often see a target in Europe and the United States appear positive clinical results, then head into, often is not aware of it---- after all, publicly published patents and related information is limited.
the original research enterprises have done what drug ability model research, what dosage forms, dose exploration, adaptation why choose A does not choose B, into the group of people why the standard is so dashed, unified two eyes a black.
This way down, in the words of the teacher, is "closed eyes to catch sparrows", "blind fish", luck to find a positive clinical data of the same adaptive disorders, bad luck on the blind.
What's more, in this state of research and development, some sea returns are still relying on their foreign resumes, every day in each WeChat group to point to each project, on their own some of the slots full of projects is double standard care, but also really can be described as "mountain bamboo shoots, mouth tip thick belly hollow."
Think again in previous years domestic enterprises to do generic drugs, copy the public release of patents to do the process, and even add impurities, I do not know that some of the original pharmaceutical factory patents, is intentionally misleading generic pharmaceutical companies, the result of domestic enterprises copied on the pit.
it feel, it's a familiar taste? Thus, if there is no short board to complement the transformation research, not in accordance with industry standards and requirements, the relevant innovation mechanism research solid, deep, thorough, those blindly promote the first in class can only be "the source is not deep and far away, root and wood long", ultimately can not explore positive results in clinical practice, more unlikely to obtain the clinicians and domestic and foreign counterparts of the real recognition.
conclusion: We've gone through a lot of detours, but mistakes are often the right foreronest, and early research on innovative drug development is much more than just "targeting."
, over the years, the strategic choice of fast follow has led to a fast-paced mindset for domestic innovative pharmaceutical companies.
For the mechanism of innovative drugs related research, or generally referred to as "find new targets, not the company's work", or stubbornly said that "following foreign large companies is enough", and even more prejudiced "research institutions, research institutions, can not be reliable."
On the other hand, many studies in the domestic academic circles, there are indeed pioneering papers, seeking new ideas, whether the newly discovered experimental conclusions are reliable, can be repeated, and regardless of the possibility of late-stage development of applied related research.
this dislocation between industry and academia may have stumbled in the early years for China's innovative pharmaceutical industry.
But now that fast follow has been completely rolled up and must really start doing first in class, if you can't make up for this short board of transformational research, then the hope that the future will lead to the birth of innovative drugs around the world in China is bound to be a long way off.
even the occasional appearance of a few self-styled "global exclusive innovations" is bound to attract endless questioning and ridicule.
to develop a truly valuable innovative drug that can't be successful like Luo Yonghao's mobile phone, or Guo Jingming's movie, by selling mouths to leeks or harvesting brain powder.
new target mechanism is really effective, clinically, peers are also looking.
The early transformational exploration and research solid, the conclusion is true and reliable, the party may lay a solid foundation for the later drug design, as well as more behind the clinical program, and finally find out a real and effective new treatment methods, access to clinicians, and then by the industry peer widely recognized, repeated and follow-up, and eventually become a new direction leading the world.
only then can we say that China's innovative drug research and development can also make a real first in class.