With the new crown vaccines of major pharmaceutical companies in the world entering Phase III clinical trials, we are not only concerned about whether the new crown vaccines will eventually be developed successfully, but also about their prices and supply issues. On August 18, the chairman of China National Pharmaceutical Group Co., Ltd. stated that after the new crown inactivated vaccine is listed, the price will not be very high, and it is expected to be several hundred yuan per injection. If you get two shots, the price should be less than 1,000 yuan. The author of this article is a well-known US pharmaceutical company R&D personnel. According to his speculation, the current US orders basically reflect the pricing of the new crown vaccine. The price of the new crown vaccine of several multinational pharmaceutical companies is much lower than this figure, ranging from 8 to 40 US dollars (The price of the two-shot vaccine).
The researcher pointed out that as for the supply of vaccines, it is basically controlled by major pharmaceutical companies in the United States and Europe. If the existing vaccines can be successfully developed in the end, China¡¯s vaccine companies may not be able to compete with them in terms of supply, and insufficient supply will restrict them from becoming an international public good.
Regarding the new crown vaccine, the most important news recently is that Russia "approved" a vaccine developed by its Gamaleya Institute. The quotation marks are used because this "approval" still has considerable restrictions. For example, it is limited to a small number of susceptible people, including medical staff and the elderly. The official release news is also relatively vague. Some officials have stated that a mass vaccination is planned in October, but the "registration certificate" issued by the Russian Ministry of Health for the vaccine requires that a large-scale clinical trial be carried out before mass vaccination.
At present, the vaccine project has only completed Phase I and Phase II trials, and the scale is only 76 people. The third phase has just started this month, and it is unlikely to be completed before October.
But this does not prevent Putin from high-profile announcement that Russia has "registered" the world's first new crown vaccine. He even revealed that one of his daughters had been vaccinated. It is also worth mentioning that this vaccine is called "Sputnik V" (Sputnik V). You know, the first artificial satellite sent into space by the former Soviet Union was called Sputnik 1. This shows that Russia has high hopes for this vaccine.
In fact, strictly speaking, this is not the world's first COVID-19 vaccine with "limited approval." As early as the end of June, China's Cansino Company issued an announcement stating that the new crown vaccine jointly developed by it and the Institute of Bioengineering of the Academy of Military Medicine of the Academy of Military Sciences has obtained the military special-needed drug approval issued by the Health Bureau of the Logistics Support Department of the Central Military Commission. In 2015, it was limited to military internal use, and the scope of vaccination could not be expanded without approval.
In addition, China has a new crown vaccine that has been used outside of clinical trials. Employees of some large state-owned enterprises can voluntarily choose injections before going abroad for business trips. There are also hundreds of employees voluntarily vaccinated within the group, including Chairman Liu Jingzhen. "I took two shots and there was no adverse reaction," he said recently.
These unconventional uses are naturally accompanied by controversy. People are still looking forward to the safety and effectiveness of these vaccines through rigorous clinical trials. Sinopharm¡¯s vaccine has started Phase III clinical trials in July. The location was selected in the UAE, with a population of 15,000. Liu Jingzhen said that the trial could be completed in three months, and optimistically expressed that it should be listed by the end of the year. Cansino¡¯s Phase III trial was launched just a few days ago and plans to recruit 40,000 volunteers in Russia, Saudi Arabia, Chile and Brazil. These tests are conducted abroad because the epidemic is effectively controlled in China, and there is no objective environment to verify the effectiveness of vaccines in China.
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The world's major pharmaceutical companies are sharpening their swords
The development of the new crown vaccine has attracted much attention, and teams from all countries are racing against time. At present, there are hundreds of new crown vaccine projects in the world in pre-clinical development work, and nearly 30 have entered clinical trials. What are they? Let's take a look.
It can be seen that 7 of the Phase III clinical trials have started, and 9 are planned to start this year. According to this situation, starting from the fourth quarter of this year, there should be results in succession.
Regardless of success or failure, this is an unprecedented speed in the field of vaccine development that often takes more than ten years of investment. All parties involved in this war have had experience in developing similar vaccines many times before, and have extensive experience in vaccine design, production and safety verification.
The idea of vaccine development is simply to let the immune cells check their eyes with the virus. When the virus comes to the door, the immune system will be able to see the right person at a glance, and will not give the virus any chance of lingering.
The most direct and traditional way is to cultivate the virus in the laboratory and beat it again until it loses its combat effectiveness, and then drag these inactivated viruses to the immune cells. The other methods do not need to use the new crown virus, nor are so violent, just let the immune cells look at the virus' weapons and equipment. The equipment that the new crown virus is eyeing by scientists is the S protein (spike protein) on its surface, which is the key to its penetration into cells, which is equivalent to a siege ladder. Immune cells are familiar with the ladder sent by the vaccine, and are ready to know how to respond next time they see the new crown virus coming with the ladder.
This S protein can be made directly in the laboratory using genetic recombination technology to make a protein vaccine. The technology is very mature, usually a large number of cells loaded with the S protein gene are cultivated so that they can produce the S protein. However, there are two companies in the above table with unique characteristics. Instead of culturing cells, they grow tobacco and extract S protein from the leaves of genetically modified tobacco. They are Kentucky Bioprocessing in the United States and Medicago in Canada.
The former is a subsidiary of British American Tobacco, an established tobacco company that produces 555 and Dunhill cigarettes. It was acquired in 2014 and developed an Ebola vaccine that year. It is said that the local tobacco farmers are particularly motivated and have a sense of pride that tobacco can also be beneficial to health.
For the same kind of tobacco, Medicago is not the same as Kentucky Bioprocessing. In addition to the S protein gene, Medicago's tobacco has other parts that can be directly assembled into a virus-like particle, which is equivalent to a dummy carrying a ladder. It is not aggressive and just imitates the appearance of an enemy.
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The new crown vaccine has been regarded as a life-saving "weapon" by various countries
In addition to whether the vaccine can be approved for listing, many companies have begun to think about another question, how to achieve sufficient production capacity?
According to estimates by the Gates Foundation, at least 10 billion doses of the new crown vaccine are needed to achieve global herd immunity. So is this possible? The most optimistic estimate for any of the above vaccines to be approved for marketing is the end of this year, while mass production will take at least until next year. Some companies have revealed their planned full-year production capacity in 2021, as shown in the table below.
Adding up the estimated production capacity of the above 13 companies in 2021 is 10.25 billion doses, which just meets the demand estimated by the Gates Foundation.
However, there are a few things to understand when seeing these numbers: 1. Not all 13 companies will be approved for listing; 2. Of course, other companies other than these 13 companies may also be approved, but they have not disclosed their own Estimated production capacity; 3. Estimated production capacity does not mean that it can be achieved; 4. Realization does not mean that everyone has a share.
It is conceivable that once a vaccine is successful, it will certainly enjoy the status of oil and natural gas. In 2009, when influenza A was raging in the United States and other places, the French Sanofi vaccine was given priority to sell to the countries that have the most vital interest in France. In addition, various forces are eyeing the vaccine to the point that Sanofi The gate of the factory needs to be guarded by military police.
The development of influenza A vaccine is relatively less difficult. It took only five months from research and development to market. Even if it has such a "strategic position", let alone the new crown vaccine. Not long ago, Moderna, a popular vaccine company in the United States, covered the logo of the company's headquarters and removed the logo outside the vaccine production base, making the outside world wonder whether it was also out of "security considerations."
The sign at the entrance of Moderna has been covered (bostonglobe.com)
Although the vaccine is still in clinical trials, a large number of reservations have been started in various countries. At present, all countries instinctively implement the "national first" plan, and book enough vaccines for their own citizens. Obviously, most vaccine development companies are from developed countries. The governments of these countries have locked in their country's vaccine supply in advance through huge R&D funding and reservation funds.
Take the United States as an example. Its government launched the "Operation Warp Speed" (Operation Warp Speed) in April, aiming to obtain at least 300 million doses of COVID-19 vaccine by the end of 2020. Through the allocation of nearly US$9 billion, the US government has ordered 800 million doses of vaccines from domestic and British and French companies.
Merck's CEO Kenneth Frazier expressed concern about this plan. He believes that the US government is exaggerating the possibility that the vaccine will be successful by the end of this year, and it will cause "extremely harmful" effects. He also called for the vaccine to benefit the world and avoid "excessive nationalism".
British AstraZeneca (AstraZeneca) also stated that its vaccines will be supplied to the country first. In order to guarantee their own supply, the four countries of Germany, France, Italy and the Netherlands launched the "Vaccine Alliance" to bet on AstraZeneca and encourage other European countries to join. Although Sanofi is a French company, the vaccines produced by its branch in the United States will be used to prioritize orders from the United States. Faced with dissatisfaction from the French side, Sanofi CEO Paul Hudson said that the US government has invested a huge amount of money to share risks with the company and deserves the priority of this batch of vaccines. He further pointed out that both China and the United States are vigorously supporting their own companies in developing vaccines. The citizens of the two countries will surely get the opportunity to be vaccinated in advance. In contrast, European governments should work harder.
To be fair, the EU has indeed made great efforts. In early May, led by Germany and France, the European Union organized a special fundraising meeting, which raised nearly 7 billion euros to fund new crown treatment and vaccine development worldwide. About 40 countries participated, including some European countries and China, Japan, Saudi Arabia and other countries. This plan does not provide priority to any country, but aims to benefit all countries in the world equally.
At present, for most countries, if they cannot develop their own vaccines, they must either pay to buy them, or cooperate with foreign pharmaceutical companies to produce them, in order to exchange vaccines with production capacity. For example, Mexico and Argentina reached an agreement with AstraZeneca to produce up to 250 million doses of vaccine to supply the entire Latin America.
Some countries also use clinical vaccines. China's Kexing is carrying out Phase III clinical trials in Brazil, which will involve 9,000 medical staff and will be managed by the Butantan Institute in Sao Paulo. According to the agreement between the two parties, Kexing promised to provide Brazil with 60 million doses of vaccines and a license for production in Brazil. On the one hand, there is no epidemic environment for clinical trials in China, and on the other, there is no vaccine. This agreement is a win-win situation.
Many countries may also need to rely on the help of international organizations, such as the COVID-19 Global Vaccine Facility (COVAX Facility) co-sponsored by the World Health Organization (WHO), the Global Alliance for Vaccines and Immunization (Gavi) and the Alliance for Epidemic Prevention Innovation (CEPI). The plan will focus on making the new crown vaccine cover 20% of the world's population. WHO Director-General Tedros Adhanom Ghebreyesus recently sent a letter to member states calling for abandoning "vaccine nationalism" and actively joining COVAX.
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The price of the new crown vaccine may not be as expensive as expected
The price of the new crown vaccine is also a concern of many people. Outsiders believe that the US orders basically reflect the current pricing of the new crown vaccine. Among the US investments listed in the table above, the funds received by Moderna and Johnson & Johnson include R&D grants and vaccine reservations. Excluding R&D grants, if only the reservations are counted, the two vaccines are average 15 dollars and 10 dollars a needle. All the money received by the other four companies is used for vaccine reservations, so the average price of a shot is calculated as Pfizer (Pfizer) $19.5, Novavax $16.6, Sanofi $21, and AstraZeneca $4. It should be noted that some vaccines require more than one shot. For example, Pfizer¡¯s vaccine requires two shots and costs 39 dollars.
Although AstraZeneca's vaccine requires two shots, it is not difficult to see that it is still the cheapest. The British pharmaceutical company announced that if its new crown vaccine is approved, it will not pursue profitability. At present, many countries have signed orders or cooperation agreements with them, all over the world. China's Kangtai Biotech also reached an agreement with AstraZeneca not long ago to produce a new crown vaccine for mainland China.
At present, only Sinopharm Group has revealed the pricing direction of the new crown vaccine. Liu Jingzhen, chairman of Sinopharm Group, recently introduced to Guangming Daily, ¡°After the inactivated vaccine is on the market, the price will not be very high. It is expected to be several hundred yuan per injection. If two injections are given, the price should be less than 1,000 yuan.¡±
Compared with the average pre-purchase price of the US government, this price is much higher. Although Liu Jingzhen emphasized that it is not necessary for everyone to fight, there are still many people who call accidents.
Of course, the prices of vaccines in different countries may not be comparable, and like the influenza A vaccine of the year, the international circulation of the new crown vaccine is by no means solely governed by economic laws. Although China and the United States are both at the forefront of vaccine development, the current situation between China and the United States makes it hard to imagine that both sides have the willingness to buy each other's vaccines.
Another example is that after Russia¡¯s controversial ¡°approval¡± of its new crown vaccine, although Vietnam and other countries can¡¯t wait to place orders, European and American countries dismissed it. Some Russian officials revealed that they had ¡°unprecedentedly¡± offered to cooperate with the United States, but the United States refused. The official blamed the distrust of the US.
This is a high-intensity competition, all players are struggling to move forward under pressure and risks. Regardless of whether it is profitable or not, once a pharmaceutical company's vaccine is successfully listed, I believe it will bring them huge returns. The market's expectations of them have also been fully reflected in the stock market. The stocks of many pharmaceutical companies are rising, and the two weeks ago of China's Cansino and Germany's CureVac went public, which has increased the bargaining chip for this competition.
Camus said in "The Plague", "You must fight in one way or another, never kneel down to beg for mercy... There is only one way to fight the plague. This truth is not commendable, it is just a matter of course. ."
From the moment the identity of the new coronavirus was revealed by Chinese scientists, the clarion call for vaccine development was sounded in multiple countries at the same time. More than half a year has passed, more and more teams have joined the battlefield. No one knows when the drums of war can stop. We only know that with modern biomedical technology weapons, in front of this invisible enemy, you can fight more actively and powerfully than ever before.