New Crown Vaccine "Dystocia": Astrazeneca Clinical Trial "Unexpected" Suspension Of Vaccine Research And Development Should Be "Fast" And "Slow"

In the spring of 2020, a new crown pneumonia epidemic is reshaping the "new normal" of all walks of life.

Due to the spread of the epidemic in the world, the lack of specific drugs and other difficulties, a variety of factors to promote the progress of vaccine research and development has become one of the most concerned industry events in the world. In the special period, in addition to R & D personnel and enterprises accelerating R & D day and night, regulatory agencies in various countries are also constantly "green light". Vaccines have become almost the only hope for people to return to the "pre epidemic era".

After the world's most coveted clinical trials, the results of vired's clinical trials are waiting for the highest degree of concern.

But accidents can also happen at any time: on September 8, local time, the clinical trial of the new crown vaccine jointly developed by British pharmaceutical giant AstraZeneca and Oxford University was suspended because of suspected serious adverse reactions in a vaccine subject.

On the same day, the CEOs of nine vaccine giants issued a historic oath, jointly promising to adhere to scientific integrity when submitting covid-19 vaccine application materials and approval applications to global regulators in the future.

Although the leading candidate covid-19 vaccine has developed to the late stage of clinical development at an alarming rate, there are still many uncertainties due to the lack of reliable clinical data so far.

Clinical trial suspension

In response to the suspension of clinical trials of new coronavirus vaccine by AstraZeneca, on the afternoon of September 9, AstraZeneca said in reply to the reporter's interview of 21st century economic news, "at present, we have started the standard review process for the ongoing global randomized control group trial of Oxford University's new coronavirus vaccine. We voluntarily suspended vaccination to ensure that the safety data of the vaccine are verified by the independent commission. This is a routine procedure to ensure the integrity of our experiments, and the necessary steps to be taken when there are any potential unexplained diseases in a trial. "

AstraZeneca described the incident as "this happens occasionally in large clinical trials, but we have to examine it carefully and independently. We are speeding up the potential impact of any single event on our research process. AstraZeneca has always been committed to the safety of participants in clinical trials and adheres to the highest standards of conduct in the trials. "

Problems in clinical trials and submitting them to an independent committee to review whether it will continue to be routine, but it is not clear how AstraZeneca will be this time. Considering that the vaccine is one of the most potential candidates, the clinical and market conditions of several other companies may also be affected.

In July 2020, interim results of the ongoing phase I / II cov001 trial, published in the lancet, showed that the vaccine (azd1222) was tolerable and produced a strong immune response against sars-cov-2 virus in all participants evaluated.

The latest development of azd1222 is August 31, when AstraZeneca announced that its clinical trial has been extended to phase III clinical trial in the United States to evaluate its safety and effectiveness. Azd1222 was invented by Oxford University and its subsidiary vaccitich.

The US trial, called d8110c00001, was funded by the advanced biomedical Development Agency (BARDA). In May 2020, AstraZeneca received more than US $1 billion from BARDA for vaccine development, production and delivery. Mene Pangalos, executive vice president of biopharmaceuticals R & D, said, "we are pleased that azd1222 has shown safety and immunogenicity in all adult age groups. If clinical trials prove that the vaccine can prevent covid-19 and is approved for use, we will strive to make it available globally as soon as possible in a fair and equitable manner. "

Clinical trial centers across the United States are recruiting up to 30000 adults over the age of 18, from different ethnic groups and regions. In addition to the United States, there are plans to recruit subjects at sites in Peru and Chile.

At present, the clinical development of azd1222 is being carried out worldwide, and late clinical trials are under way in the UK, Brazil and South Africa, and trials are planned to start in Japan and Russia. These trials, as well as phase III clinical trials in the United States, were previously expected to recruit 50000 participants worldwide. Based on infection rates in the clinical trial community, the results of later trials are expected to be available later this year.

All parties were full of expectations for the vaccine until the "accident" appeared.

Supply and market

On September 4, Nature Reviews Drug Discovery released a review on the progress of new coronal vaccine research and development, saying that as of September 2, 2020, the global covid-19 vaccine research and development pipeline includes 321 candidate vaccines. Among them, 32 vaccine candidates are in clinical trials, and more than 280000 participants from at least 470 locations in 34 different countries are planned to be recruited.

Currently, the fastest-growing clinical candidate vaccine is undergoing phase III clinical trials, and data supporting the approval are expected to be available later this year. These fast-growing candidate vaccines have begun mass production and, if approved, can be quickly distributed.

At present, most of the vaccine candidates in clinical trials use the spike (s) protein and its variants as the main antigens. However, candidate drugs targeting other or multiple antigens are being developed, including targeted N protein, attenuated vaccine, inactivated vaccine and peptide vaccine.

Since April, the biggest change in the general profile of new crown vaccine developers has been the increasing number of large multinational companies involved. Currently, among the clinical candidate vaccines, 11 are developed by Chinese institutions, and 7 are supported by the U.S. action warp program, which aims to deliver 300 million doses of vaccine for covid-19 by January 2021. So far, more than 10 billion US dollars have been announced for promoting vaccine development.

The global race for quick success and instant benefit has worried the industry about its safety and effectiveness. To this end, on September 8, the CEOs of nine Biopharmaceutical Enterprises, including AstraZeneca, biontech, GlaxoSmithKline, Johnson & Johnson, Merck, Moderna, Novavax, Pfizer and Sanofi, announced a statement and signed the following oath: "the safety and effectiveness of vaccines, including any potential risks All covid-19 vaccines, including the covid-19 vaccine, are evaluated and confirmed by professional global regulatory agencies, such as the U.S. Food and Drug Administration (FDA). "

FDA requires that the scientific evidence for regulatory approval must come from large-scale, high-quality, randomized, blinded trials, with appropriate study design and wide participation of multiple populations.

Taking AstraZeneca as an example, in order to expand the scope of supply, many cooperation agreements have been signed in the world. The Supply Announcements signed with Russia, South Korea, Japan, China, Brazil, Latin America, etc. have brought the global supply of the vaccine to 3 billion doses.

In China, in August this year, Shenzhen Kangtai Biological Products Co., Ltd. announced that it had signed the binding transaction term sheet with AstraZeneca. AstraZeneca exclusively authorized Kangtai bio to develop, produce and commercialize the licensed products in the people's Republic of China (excluding Hong Kong Special Administrative Region, Macao Special Administrative Region and Taiwan region).

At the same time, Kangtai bio ensures that it can produce at least 100 million doses per year by the end of 2020 and at least 200 million doses per year by the end of 2021.

On September 9, under the influence of clinical suspension, Kangtai bio once fell by 19.66% and reached the limit. On the same day, it closed down by 16.57%, and its latest market value was 108.9 billion yuan. In the afternoon of the same day, Kangtai Bio said that the scale of the trial of AstraZeneca vaccine was the largest, and the occurrence of individual cases was a normal phenomenon in the research and development, which did not affect the promotion of the cooperation with AstraZeneca.

But can not stop the market, Kangtai biological "lead" vaccine stocks fell together. As of the end of the day, Zhifei biological products fell by 11.91%, Weiming pharmaceutical industry by 10.02%, Wantai bio by 10%, Hualan bio by 8.87% and Watson by 8.51%.

China is the second largest vaccine market in the world. However, compared with the mature market, China's vaccine per capita expenditure and coverage rate (vaccination rate) are lower. According to iqvia data, the total scale of the global vaccine market is about 36 billion US dollars, of which the US market share accounts for the largest share, reaching 33%, and the Chinese market share accounts for 11%, about US $4 billion.

China's vaccine market has achieved a growth rate of about 10% in the past six years. With the introduction of class II vaccines (self funded vaccines), especially more innovative vaccines, the overall market will maintain stable growth in the future.

In the past five years, there have been several first-class vaccine safety accidents, which makes the state pay more attention to the management and control of key links such as vaccine registration, production, procurement, circulation and vaccination, which puts forward higher requirements for vaccine enterprises.

In June 2019, the State Council formally enacted the most stringent supervision of the vaccine management law in history. The policy emphasizes the whole process supervision, forbids commissioned production, encourages R & D innovation, encourages the scale and intensification of vaccine production, optimizes the industry structure, strictly promotes the centralization of market access, and implements the compensation system for abnormal reaction of vaccination.

After several stages of rapid development, adjustment and transformation, the development mode of China's vaccine market tends to be healthy.

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