How far has the development of "domestic vaccine" progressed?
What is the "wall"?
July 21, 16:27
A vaccine that is a pillar of measures against the new coronavirus.
Vaccines are being inoculated in Japan as well, but all of them are vaccines developed overseas.
So far, new corona vaccines have been put into practical use one after another overseas such as the United States, the United Kingdom, China, Russia, India, and Cuba.
On the other hand, although domestic pharmaceutical manufacturers are continuing to develop vaccines, they have not yet reached practical use.
While some people have said that it may be a de facto "vaccine defeat," the field of domestic vaccine development continues to seek to overcome major barriers.
We interviewed the front line to see how far the development of domestic vaccines has progressed.
(Reporter, Ima Mitani, Faculty of Science and Culture)
Domestic vaccine development Four companies have advanced to clinical trials
As of July 20, the following four companies have reached the "clinical trial" of actually administering the new corona vaccine to humans by domestic manufacturers.
●
Promote the development of
Osaka's bio-venture companies “AnGes” and
“DNA vaccine (* 1)”.
It was the earliest domestically to enter clinical trials, and is currently in the "Phase 2/3" stage of the three stages (Phases 1, 2, and 3) of clinical trials required to approve a new drug.
●
Promote the development of
“Shionogi”, a major pharmaceutical company in Osaka, and
“genetically modified protein vaccine (* 2)”.
We are conducting a clinical trial called "Phase 1/2".
●
Promote the development of
major pharmaceutical companies “Daiichi Sankyo” and
“mRNA vaccine (* 3)”.
We are conducting a clinical trial called "Phase 1/2".
●
Promote the development of
Kumamoto's pharmaceutical companies “KM Biologics” and
“inactivated vaccine (* 4)”.
We are conducting a clinical trial called "Phase 1/2".
In addition, the venture company "VLP Therapeutics Japan" submitted documents for conducting clinical trials to the examination body in July using a method called "RNA vaccine" using its own technology.
In addition, there are cases where Japanese researchers conduct clinical trials in Japan in collaboration with overseas companies, but none of the vaccines produced by domestic manufacturers has been put into practical use yet.
The "wall" of domestic vaccine development is "large-scale clinical trials"
"Large-scale clinical trials" are a major barrier to the development of domestic vaccines.
Vaccine development involves large-scale clinical trials involving tens of thousands of people to confirm efficacy and safety.
While conventional drugs are used to treat illness, vaccines are given to healthy people, so their efficacy and safety need to be fully confirmed.
Vaccines from companies such as Pfizer, Moderna, and AstraZeneca, which have already been put into practical use, have undergone large-scale clinical trials on the scale of tens of thousands of people.
These clinical trials are divided into a group that receives the vaccine under development and a group that receives the non-vaccine "placebo", and participants are not informed of which one they received.
After that, we will investigate whether there is a difference in the number of people who develop the new coronavirus after inoculation and whether there is an increase in harmful symptoms.
In clinical trials, not limited to vaccines, even groups inoculated with "placebo" may have reactions that seem to be effective or have symptoms such as side reactions, so this method is used. It is necessary to check strictly.
Japan lacks know-how on "large-scale clinical trials"
However, in Japan, there have been few cases in which new vaccines developed in Japan have been put into practical use recently, and the know-how for conducting large-scale clinical trials of tens of thousands of people has not been sufficiently accumulated.
It's not easy to build a system suddenly after facing a pandemic.
In latecomer Japan, there are also "ethical" issues
Another reason why large-scale clinical trials are difficult is the "ethical" issue.
It has been pointed out that it is ethically unacceptable to administer a "placebo" for testing in the presence of vaccines that have already been put into practical use, such as Pfizer and Moderna.
Approximately half of the people who participated in the study may have been vaccinated with a "placebo" that is completely ineffective, even though there are vaccines available, and it is difficult to get a vaccine that works during the observation period. ..
What to do then?
Masayuki Hikita, general manager of Biologics, who is in charge of vaccine development at Daiichi Sankyo, cites a method called "non-inferiority trial" as an alternative to large-scale clinical trials.
Daiichi Sankyo General Manager Masayuki Hikita
"It is currently difficult to conduct verification tests in tens of thousands of cases. Under such circumstances, immunogenicity was confirmed in" non-inferiority tests "at the level of thousands of cases, and vaccines were used. I would like to verify the effect of the vaccine. I would like to get the data that the antibody that protects the new corona virus is properly produced by hitting the vaccine and that there is no difference from the previous vaccine. "
What is a "non-inferiority test" that can be done in Japan?
What kind of test is a "non-inferiority test"?
In the "non-inferiority trial", the "group vaccinated under development" and the "group vaccinated with a vaccine that has already been put into practical use" are compared.
By comparing the values of neutralizing antibodies that suppress the action of the virus in these two groups and confirming that the vaccine under development is comparable to the vaccine in practical use, it is effective and safe. Etc. can be confirmed.
This way you don't have to inoculate a "placebo".
However, in order to actually conduct clinical trials using this method, it is necessary for the government to approve it, and for internationally, the results of clinical trials conducted using this method must be approved.
Final stage clinical trials How do companies respond?
Other pharmaceutical manufacturers also face the challenge of difficult large-scale clinical trials.
Each company is considering how to conduct final-stage clinical trials.
● Shionogi
Pharmaceutical President Isao Teshiroki of
Shionogi
Pharmaceutical said in an interview with NHK in June that he would consider the ideal form of clinical trials based on national policy. I was talking.
Mr. Isao Teshiroki, President of Shionogi Pharmaceutical Co., Ltd.
"For example, while confirming the safety of 2000 or 3000 people, confirm that neutralizing antibodies and cell-mediated immunity are comparable to those of Pfizer and Moderna vaccines. We will continue to accumulate data on a yearly basis even after it has started. "
After conducting final-stage clinical trials in the form of "non-inferiority trials", whether the vaccine is effective or if there are any unexpected side reactions even after the vaccine is actually used, etc. It is said that preparations are being made in the direction of establishing a system to check all cases.
● KM Biologics
KM Biologics believes that it is best to confirm in the form of a "non-inferiority test" after discussing with PMDA = Pharmaceuticals and Medical Devices Agency, which reviews drugs. ..
In order to deal with future mutant viruses, the company aims for approval by a method called "prototype vaccine" that enables rapid development of new vaccines by receiving approval in advance for standard manufacturing methods and quality control methods themselves. It's called.
We will apply for approval in the summer of 2022 and aim to put it into practical use by the end of 2023 at the latest.
● AnGes
MG also wants to consider how large-scale clinical trials should be conducted, based on the trends of international discussions such as PMDA.
Overseas, some manufacturers have adopted "non-inferiority test"
Some overseas pharmaceutical manufacturers that are developing vaccines as a latecomer have already adopted "non-inferiority trials".
One of these, France's Barneva, has announced that it will conduct a "non-inferiority trial" on the vaccine under development.
Approximately 2000 people will receive the vaccine under development, and approximately 1000 people will receive the AstraZeneca vaccine, so it is said that the neutralizing antibody levels will be compared two weeks after the two doses.
Movement to recognize "non-inferiority test" internationally
Under these circumstances, the movement to accept "non-inferiority trials" is spreading.
According to the Ministry of Health, Labor and Welfare, ICMRA, an international collaborative organization of regulatory authorities in about 30 countries and regions, is a "non-inferiority trial" with thousands of people as an alternative to large-scale clinical trials. Was discussed, and it was generally agreed to adopt such a method.
A person in charge of the Ministry of Health, Labor and Welfare explains, "We are not creating a method that sets and approves our own standards only in Japan, but we are creating a new evaluation method while obtaining international agreement."
In Japan, there are almost no cases where new vaccines developed in Japan have been put into practical use since the end of the 1980s.
However, according to the national long-term strategy for vaccine development and strengthening of production system, which was approved by the Cabinet in June, "Infectious disease research has been tapering off in both industry, government and academia. There was a lack of investment and policy making in irrational fields, "he said, and stated that he would" strongly support the government "to expedite the development of a new domestically produced corona vaccine.
According to the Ministry of Health, Labor and Welfare, the agreement at ICMRA to allow "non-inferiority testing" was also realized by a proposal from Japan.
To realize a domestic vaccine "Japan has finally begun to move"
It is the Institute of Medical Science, the University of Tokyo, who is a leader in vaccine development in Japan and is also participating in the development of the new corona vaccine, who is looking forward to the movement of such national support toward the realization of domestic vaccines. This is Professor Ken Ishii.
Professor Ishii had previously been developing an "mRNA vaccine" for MERS = Middle East respiratory syndrome (an infectious disease caused by the same coronavirus as the new coronavirus) in collaboration with Daiichi Sankyo and others. I have had the experience of not being able to proceed to clinical trials in humans due to lack of support such as.
However, he says he feels different this time.
Professor Ken Ishii, Institute of Medical Science, The University of Tokyo
"Now, we can see the national intention to develop domestic vaccines, and pharmaceutical companies are advancing in response to that, sharing a sense of crisis and making the utmost efforts. Finally, the heavy waist has begun to move. If the throat is too high, the heat will not be forgotten, and the question is whether it can really be realized. The new corona may need to be vaccinated every year from now on. The current vaccine has been confirmed to be safe and highly effective, but it is important to aim for a safer vaccine and to have a sense of security as a domestic brand. Also, although I was able to purchase it from overseas this time, I will continue to purchase it in the future. There is no guarantee, and the health and security of the people is necessary. "
"Vaccine development" will also be used for new drug development in the future
In the development of the new corona vaccine, not only the conventional technology but also the latest technology such as "mRNA vaccine" was put into practical use at once.
These technologies are expected to lead to the development of new medical technologies in the future.
We also heard from the pharmaceutical manufacturers we interviewed that they were looking ahead to the future.
Daiichi Sankyo General Manager Masayuki Hikita
"The technology of" mRNA "can lead to drug development at a high speed. Currently, the new corona vaccine is prioritized, but other vaccines are also being worked on, and the gene therapy area. I think we should also promote its application to the oncology field. I want to become a leader in this field. "
The development of domestic vaccines has fallen behind overseas manufacturers.
However, overcoming the big barrier here and whether or not a domestic vaccine will be realized will be the key not only to advance the fight against the new corona but also to pave the way for new drug development in the future. It may be.
Glossary
* 1 << DNA vaccine, RNA vaccine >>
A new type of vaccine that administers DNA and RNA that produce viral proteins.
Gene therapy technology is being applied.
* 2 << Genetically modified protein vaccine >>
A vaccine that artificially produces viral proteins.
The virus itself is not used.
It is used in herpes zoster vaccines.
* 3 << mRNA vaccine >>
A vaccine that uses a substance called "mRNA" that contains the genetic information of the virus.
In the new corona, Pfizer and Biontech groups and Moderna have put it into practical use as a vaccine for the first time.
* 4 << Inactivated vaccine >> A vaccine made
by chemically treating an actual virus to lose its infectivity and pathogenicity.
This method is used in many vaccines such as influenza vaccine.
Science and Culture reporter
Mitani維摩
2009 it joined
Tokushima stations, incumbent through the Osaka stations
responsible for the medical field