The first domestic mRNA vaccine was approved, but who was vaccinated?

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On March 22, 2023, CSPC Pharmaceutical Group (1093. HK) disclosed that after the recommendation of the National Health Commission and the organization of the State Food and Drug Administration, the company's new crown mRNA vaccine was included in the emergency use in China.

This new crown mRNA vaccine has completed phase I and II clinical trials in China, as well as clinical studies of sequential booster immunization (that is, booster shots with different technical routes). CSPC has obtained emergency approval from the State Food and Drug Administration since April 2022 to start clinical trials.

Looking back at the beginning of the new crown epidemic, China has laid out a total of 4 new crown vaccine technical routes. Inactivated vaccine, adenovirus vector vaccine, recombinant protein vaccine these three technical routes have successively had products, the fourth route is nucleic acid vaccine, no product has been approved, the mRNA vaccine independently developed by CSPC has become the first.

As of press time, when this vaccine will be launched in various places, as well as the applicable age range and vaccination method, as of press time, CSPC Pharmaceutical Group has not replied.

There are still many new crown vaccines with the same technical route in China, and a brokerage analyst analyzed "Financial Health", whether more new crown mRNA vaccines can be expected to be launched in the follow-up still depends on the progress of the review, and may be more likely than before.

The first domestic new crown mRNA vaccine

On March 22, on the website of the China Clinical Trial Registry, Caijing Health retrieved a total of 4 clinical trials of CSPC's new crown mRNA vaccine.

The above four clinical trials were all registered in 2022. Participants in the trials included adults aged 18 to 59 years and studies in older adults aged 60 years and older.

According to CSPC Pharmaceutical Group, the results of clinical studies in more than 5,500 people have proved the safety, immunogenicity and protective efficacy of the company's new crown mRNA vaccine.

For safety, the adverse events of this new crown mRNA vaccine were low and mild, and the adverse events were mostly fever and pain at the injection site, and mainly primary and secondary.

In the clinical trial of CSPC's new crown mRNA vaccine, compared with the adult group, the incidence and severity of adverse events in the elderly group were reduced, and they had a better risk-benefit ratio in the elderly population.

From the results of clinical research, CSPC summarized that basic immunity and sequential booster immunization, and the new crown mRNA vaccine can continuously induce specific T cell immunity against wild strains, Delta, Omicron BA.2 and BA.5 strains, and maintain high levels for a long time, and the cellular immunity against different strains is roughly the same.

From October 2022 to January 2023, in 4,000 booster clinical studies carried out during the new crown epidemic, the protective efficacy of the new crown mRNA vaccine was 70.2% 70.2% from 7 days to 28 days after booster vaccination. 14 to 28 days after booster vaccination, the protective efficacy was 85.3%.

This new crown mRNA vaccine can be stored for a long time at 2-8°C.

The principle of the new crown mRNA vaccine is that the spike protein on the surface of the new crown virus is an ideal target for the vaccine, and the vaccine sends the mRNA molecule encoding the antigen into the human cell, and the corresponding antigen protein is produced after translation in the cell, which then triggers the immune mechanism.

Compared with traditional technical routes such as inactivated vaccines, mRNA vaccine technology is new and depends on the research and development level of the industry. For this reason, the biotechnology industry has been looking forward to the introduction of domestic mRNA vaccines.

Self-expense, is it a solution?

After this domestic new crown mRNA vaccine is included in the emergency application, the next step is to spread it to all parts of the country and start vaccination for ordinary people.

Contrary to the industry's euphoria about the new technology, the public's attitude towards the new crown mRNA vaccine is calmer. A woman in her 50s who received two doses of inactivated vaccine and was infected with the new crown at the end of last year bluntly told "Finance and Health", "I have all had the new crown, it's okay for the time being, I won't get it." Another 31-year-old man also said that there is no coronavirus epidemic at the moment and he does not think he needs to consider vaccination. He has not been vaccinated against the new crown and has been infected with the new crown virus.

Most Chinese have already been vaccinated. As of February 23, 2023, a total of 3.426 billion doses of new coronavirus vaccine have been reported nationwide, with a total number of 1.31 billion vaccinated, and 1.277 billion people have been fully vaccinated, accounting for 92.95% and 90.58% of the total population of the country, respectively. A total of 850 million people have completed booster immunization.

According to the National Health Insurance Administration's "2022 Medical Security Development Statistical Express", from 2021 to 2022, the cumulative settlement of new coronavirus vaccines and vaccination expenses nationwide will exceed 150 billion yuan.

Many people in the industry have estimated at the beginning of 2022 that the cost of some companies may not be recovered in this wave of new crown vaccines. For those that went on the market later, such as the new crown vaccine that was approved at the end of 2022, "basically no one expected them to make money."

And so it is. Kangtai Biotechnology(300601. SZ) released a performance forecast at the beginning of 2023, and it is expected to lose 76 million yuan to 150 million yuan in 2022, which will turn from profit to loss compared with 2021. As for the reasons for the loss, the new crown vaccine project is not optimistic, due to major changes in the vaccination environment at home and abroad, sales have fallen sharply, and the company has reduced its profit by about 800 million yuan. The company's vaccine was approved for emergency use in May 2021 and initially made good money, until the second quarter of 2022, when the narrative took a sharp turn and sales of the new crown vaccine fell rapidly.

On the other hand, the price of the new crown vaccine itself is gradually falling. China is free of charge for all people, which is jointly borne by the financial department and the medical insurance department.

At first, the per capita cost of the new crown vaccine was about 200 yuan. In March 2021, the Hunan Medical Insurance Bureau released information showing that vaccines are calculated according to 180 yuan per capita, and vaccination costs are calculated by 20 yuan per capita, with a total of 200 yuan per person, with a financial burden of 30% and medical insurance covering 70%.

As more coronavirus vaccines are launched, the average price is getting lower and lower. On March 9, 2023, the official website of the National Health Insurance Administration released the "2022 Medical Security Development Statistical Express", which mentioned that it led price negotiations with vaccine manufacturers, and the price benchmark of a single dose of inactivated vaccine, recombinant protein vaccine and adenovirus vector vaccine was unified to about 16 yuan.

Nowadays, people's willingness to vaccinate is not as strong as in the early days of the epidemic, coupled with the variety of vaccines and low competitive prices, despite the breakthrough of the technical route, the new crown mRNA vaccine may still face a situation where it cannot be recovered.

"Now is not an economic act, no manufacturer can do it." The above-mentioned brokerage said.

Some voices in the industry call for the routine and market-oriented operation of the new crown vaccine, that is, it will become a vaccine that is self-funded, speculating that there may be a turnaround from the second half of this year to next year. On March 22, a person close to the disease control system said that free vaccination is still being implemented, and as for the aforementioned speculation, "I have not heard of it."

Yu Xuefeng, chairman and CEO of CanSino Biologics, also told Caijing Health on March 22, "Of course, we hope to open up the private market. ”

CanSino's new crown mRNA vaccine is still in line. At present, it is in the clinical phase II b stage, and the safety and immunogenicity data as a sequential booster dose were obtained two months ago, and the next stage of R&D planning will be carried out in the future according to the epidemic situation, national immunization strategy, review mechanism, etc.

In the long run, the breakthrough of Chinese manufacturers in the mRNA technology route is still necessary, which is also one of the future technical directions in the field of biotechnology, so that in 2021, the industry experienced a round of rapid progress, this year 18 mRNA companies around the world obtained more than 2 billion US dollars in financing, and China's new crown mRNA companies even completed three rounds of financing a year, with a total financing amount of more than 1 billion US dollars. By the middle of 2022, the surging boom had fallen, and an investor told Caijing Health that the aforementioned valuation level in the primary market in 2022 is almost impossible to melt.

2021 was a breakthrough year for the mRNA field, with two mRNA vaccines developed by Pfizer, BioNTech and Moderna receiving emergency use authorization, and the global sales of the two vaccines reached $58.7 billion, far exceeding the sales of other coronavirus vaccines.

Abogen Biosciences, founded in early 2019, was once the most promising Chinese biotechnology company to come up with mRNA vaccines. In August 2021, its Series C financing exceeded US$700 million, setting a new pre-IPO record for local pharmaceutical companies. However, the data collation and statistical analysis of the domestic phase III clinical trial of the new crown mRNA vaccine cooperated by Apest Biologics and Watson Biotech has entered a long end, and it seems that the commercialization time window has been lost.

The broad-spectrum new crown mRNA variant vaccine (S protein chimera) developed by Watson Bio and Lanque Biotechnology has entered phase III clinical trials.

In March, the phase I clinical trial of the novel coronavirus mRNA vaccine developed by Sinopharm China Biotech (Shanghai) Co., Ltd. was officially launched. The company said that the phase I clinical trial of the new crown mRNA vaccine uses a randomized, double-blind, placebo, and active control design to evaluate the safety and immunogenicity of the vaccine in healthy people aged 18 years and older.

CSPC is a successful case of traditional pharmaceutical companies across borders. Some self-media said that it developed mRNA vaccines with the efficiency of generic drugs, and at the same time did its own upstream supply chain. In November 2022, the company revealed that it had built a GMP-compliant production workshop and obtained a drug production license issued by the Hebei Provincial Food and Drug Administration to ensure the supply of vaccines. In addition, key raw materials and auxiliary materials are produced by the Group, which has achieved independent control in the supply chain and greatly reduced production costs. That is, high-cost raw materials such as modified uridines and liposomes can already be synthesized internally, and the cost of future vaccine production is lower than that of the inactivation route and the recombinant protein route.

In addition to the new crown vaccine, another application area of mRNA technology is tumor treatment.

On February 22, 2023, Merck announced that the tumor neoantigen mRNA vaccine mRNA-4157/V940+PD-1 antibody combined with adjuvant treatment of high-risk melanoma to prevent postoperative recurrence has obtained breakthrough therapy certification from the US Food and Drug Administration (FDA).

In China, there are also companies that have made progress, such as the website of the Drug Evaluation Center of the State Food and Drug Administration on March 15, Beijing Likang Life Science Co., Ltd.'s personalized tumor neoantigen vaccine product LK101 injection has been approved to enter the clinical stage.

Of course, these Chinese companies are still a few years away from the use of mRNA tumor vaccines.

Text / Zhao Tianyu

Ed. / Wang Xiao