Drug guidelines knock on some people who are still pretending to be asleep in the risk and bubble, and it's time to wake up
Tidying up / Shinna
Editor / Wang Xiao
Photo/pixabay
"What clinical problems can be solved?"
This is a question that must be answered at the first time for a new drug, and it is also a clear requirement put forward in the "Guidelines for Clinical Research and Development of Antineoplastic Drugs Oriented to Clinical Value (Draft for Comment)" issued by the Drug Review Center of the State Food and Drug Administration in July 2021.
Photo: Drug Evaluation Center of the State Drug Administration
This draft is known as the "Drug Guide", and as soon as it was launched, the stock prices of many listed pharmaceutical companies fell in response.
A person close to the drug regulatory system has his own understanding, "The new drug research and development market does accumulate some bubbles and risks, and the guidelines only wake up some people who are still pretending to be asleep, and it is time to wake up."
What is a good drug, what problems do pharmaceutical companies need to solve, and how will China's new drug research and development industry develop in the future? We chatted with this person who is close to the drug regulatory system, trying to understand the considerations behind the regulator's policy formulation and thinking about the environment for new drug development in China.
<h1 class="pgc-h-arrow-right" Data-track="19" what is the clinical value >? </h1>
From the patient's point of view, the approved drugs are better than one, which is more effective, safer, more convenient or more accessible, which is the clinical value. But we have also seen some phenomena that are unfavorable to patients.
For example, some companies take the results of clinical trials that were done many years ago and declare them now. The clinical value of this drug may be very limited at the moment.
Exactly what is the clinical value, at this time, the approver and the enterprise will have a big disagreement. One of the things we learned earlier was that the approval team believed, "Your product has limited clinical value." Companies will say, "After the clinical trial of my product is done, the result is positive, why don't you approve it." "There are also a lot of disagreements among experts, and there are some experts involved in clinical trials, and his opinion may not be objective.
Of course, companies will feel that their products are good, and ignore some of the defects of the products. For example, the original positioning of the drug is me-better, and finally did not reflect the advantages in the clinic. For example, the original compound has been optimized, but the efficacy and safety are similar, or even worse.
At this time, it is necessary to explain what is the clinical value objectively, fairly and systematically, and the evaluation center is now equivalent to throwing out this orientation, so that everyone can rationally evaluate the clinical value and make trade-offs for some projects that have obvious clinical value limitations. Perhaps some companies can bear the pressure and risk, insist that after the test, if they are not satisfied with the results of the test, they will not mediate and automatically give up. This creates a virtuous circle that is helpful for the pharmaceutical industry as a whole.
The perception of certain types of drugs may be just a few numbers, such as the anti-tumor drug PD-1. However, the feelings of enterprises and regulatory authorities are very direct, the competition is extremely fierce, and thousands of troops have crossed the single wooden bridge. Both sides are under a lot of pressure.
Photo/unsplash
Before the reform of the review and approval system, some enterprises got clinical approvals to "fool" investment, not really to do this drug; some companies did not know what to do next after getting the approvals. Some products have made some data, prompting that it is of little significance to continue to do, but still do not give up, and began to find a takeover, the reason is that the company does not accurately judge the clinical value, or the wrong judgment of the industry environment prospects.
Once on the track, it's not easy to persuade anyone to let go, because a lot of money has already been invested in it, such as the PD-1 track. In addition, it is necessary to have the vision that if the clinical value of the product is limited, even if the "positive" result cannot pass.
This requires reminding enterprises of risks, from the project level to maintain rationality and forward-looking - expected clinical value is limited or clinical advantages are not enough prospective products do not invest, has been x companies are carrying out trials, if the expected clinical value is limited, to boldly break the arm, because the international mature research and development environment has been stop earlier, stop cheaper, equivalent to resource optimization. The resulting drug has high clinical value and is more competitive.
In this way, there will be no situation where a disease has ten products on the market, and if a dozen drugs compete for an indication, all companies may sacrifice quality, lower standards, and form an inner volume in order to seek speed.
<h1 class="pgc-h-arrow-right" data-track="94" > clinical trial standards will not be lowered</h1>
The standard of clinical trials, once raised, will not be lowered.
The criteria for drug supervision and approval are also becoming more and more clear - the drug regulatory authorities do not control the maximum number of drugs approved for a disease, but will use the same standards to approve in the same period.
Now the domestic situation is that there are already better drugs in the clinic, but when companies do clinical trials, they still want to compare with drugs with poor efficacy, because it is easier to win than this. The clinical value-oriented guidelines, although they do not say that new drug research must be compared with the best drugs, but also let everyone have a generation, and who can reflect the clinical value of their own products to think.
In China, there are not so many companies that know how to advance and retreat, their pressure is too great, they may not get the next node or the product is not listed, and the company is gone.
However, it's like eating, already eating refined foods, it's unlikely to go back and eat wild vegetables, and this must be considered for both patients and participants in trials.
If an indication is only imported drugs, the drug regulatory authorities usually do not require clinical trials of other domestic drugs to be head-to-head with imported drugs, which is too high for Chinese pharmaceutical companies now.
However, if there are already domestic drugs in the treatment in this field, and they are widely used, the next step is to consider improving clinical value. It is equivalent to a race, someone has already run to the finish line, whether people who have just arrived on the track are allowed to start, especially if there are already many runners on the track. If allowed, the standard will be lowered endlessly, and the quality and efficacy of the drugs on the market will not be improved.
In this regard, the attitude of the drug regulatory department is very firm, and it has also been recognized by clinical experts and doctors - clinical experts always do similar clinical trials and will feel worthless. For subjects, to participate in a clinical trial, the control group is currently a relatively poor treatment, which is also unethical, if the control group is the best treatment at present, and the trial group may be better or not worse, then the drug supervisor, doctors and patients welcome the design of the trial and drug.
In fact, there have been standards before, but sometimes the door is not closed thoroughly, or inexperienced companies do not understand and repeat the same mistakes. Some companies have a false expectation that "others are doing this, I can too.". What they don't take into account is the change in clinical practice – so many effective drugs have been approved, why compare to the worst? Sometimes it's a fluke that I don't think this request will fall on me.
This drug guide, which clearly puts forward this point and is based on the patient's point of view, is very valuable. Companies either need to be more forward-looking, or they need to move forward with projects faster and conduct differentiated R&D. If this indication is no longer valuable, do something else that may be valuable and optimize new drug research and development resources.
<h1 class="pgc-h-arrow-right" data-track="95" > the big reshuffle of new drug research and development</h1>
Previously, there were not so many drugs piling up to do clinical phase III. Since the reform of drug review and approval has changed the approval method of clinical trials, from the approval system to implied permission, which has greatly released the space for clinical research and development, just like now everyone can go to school, many people can enter the university.
One of the things I learned from the drug regulatory department is that at the beginning of this year, some companies communicated and proposed to do first-line treatment for lung cancer. The reply received by the enterprise is that it has now approved imported products for this indication, as well as domestic products. Clinical trials have to go and chemotherapy, and this design has not been accepted.
Conducting a clinical trial with limited expected clinical value is a great risk for the enterprise. Phase III clinical trials are theoretically invested in 100 million yuan, a case of subjects, if calculated according to 500,000 yuan, a clinical trial contains 400 cases of subjects, the overall cost is 200 million yuan.
New drugs want to pass the review, to answer what is brought to the patient, what problems are solved. Such as that disease, which stage, compared with the existing drugs, what advantages, what problems are solved, and how much clinical value this new drug has.
Companies provide a high-value drug through scientific research and experimental data. For example, the drug with the best efficacy is better than the current effect; or the efficacy is similar to it, but it is safer or more convenient, such as the original use once a week, and now it can be done once a month, which is clinical value.
This clinical value is the general consensus of the main regulatory countries, and the relatively mature regulatory environment, enterprises will consciously follow this principle.
Figure/pexels
In the future, most domestic pharmaceutical companies still have to do the domestic market first, and the top students will have the opportunity to go to the international PK. The pharmaceutical industry can't eat fat in one bite, it needs an experienced team, not just scientists in a certain field can make medicine. Experience also includes research, translation, reporting and dealing with national regulators.
Now the fierce competition in R&D and the concept of reviewing international results have made companies feel pressure and challenges. One of the things I learned is that sometimes the drug regulatory department puts forward a request for a clinical trial, and some companies want to do it, but they really say with tears that they can't do it.
Domestic pharmaceutical companies are in a major reshuffle stage. Now that the standards are very clear, the competition will be more intense. As the policy environment changes, all pharmaceutical companies are first able to survive, and then different products enter the key track. Several large pharmaceutical companies already have a certain scale and may be able to go all the way.
Clinical approval is not tall at all, and clinical value is the last word. For start-ups, the ideal scenario is to develop a product of clinical value, either independently, or in collaboration with others or to be acquired.
In the future R&D regulatory environment, as well as the current listing rules of the science and technology innovation board, it is difficult for enterprises with insufficient innovation to stand out, and it is difficult to give birth to pharmaceutical start-up unicorns, of course, enterprises need reasonable profits to maintain stable investment. In the field of medical technology, Europe and the United States are still at the forefront, and the domestic government should be in step with each other, and the investment should be more rational to improve the core competitiveness of medical technology companies. It is hoped that the overall environment will be more conducive to the virtuous circle of the industry and pave the way for China's "healthy 2030".
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