[현장생중계]Ministry of Food and Drug Safety briefing on results of AstraZeneca Vaccine Advisory Group

[김상봉 / 식품의약품안전처 국장]

The verification advisory group is a procedure in which the Ministry of Food and Drug Safety collects advisory opinions from various experts on clinical, nonclinical, quality, and other fields prior to consulting the Central Pharmacy Review Committee.This verification advisory group includes infectious medicine specialists, vaccine experts, and clinical statistics experts. Eight people attended.

Results of clinical trials. There were 4 clinical trial data submitted in the UK, 1 in Brazil, and 1 in South Africa. The results of two clinical trials conducted in the UK and Brazil for the effectiveness evaluation and 4 clinical trials for the safety evaluation were integrated and analyzed.

The clinical trial subjects included in the effectiveness analysis were 8895 adults 18 years of age or older who were negative for the COVID-19 virus and received two standard doses.

As a result of analyzing the characteristics of the target group participating in the clinical trial, the average age was 42.2 years, 37% of people with underlying diseases such as obesity, cardiovascular system, and respiratory system, and 660 people over 65 years old, 7.4%.

For the preventive effect, the proportion of patients infected with COVID-19 occurred in each group from the 15th day after the vaccine and the control drug were administered twice, and one or more clinical symptoms such as high fever and cough were expressed, and the result of the corona 19 virus test was confirmed. If so, the infection was defined as confirmed.

As a result of the evaluation, the number of confirmed COVID-19 patients was 27 vaccine groups and 71 control groups, which showed a prophylactic effect of about 62%, which is a result that satisfies the domestic and international standards related to the evaluation of the effectiveness of the COVID-19 vaccine such as WHO, i. is.

When analyzing the preventive effect according to the administration interval, the wider the interval, the more the preventive effect and immune response tended to increase. In addition, in the vaccine group, severe symptoms related to COVID-19, hospitalization, use of the intensive care unit, and death did not occur, but 4 people were hospitalized in the control group.

As an indirect indicator that can predict vaccine effectiveness, the immune response, such as the type and amount of antibodies produced in the body after vaccine administration, was evaluated in 2398 people.

The binding antibody value, which indicates the amount of antibody that binds to the corona 19 virus antigen, increased 503 times after 2 doses of the vaccine, and 99% or more of the subjects showed a seroconversion rate that increased the antibody price by more than 4 times compared to before administration.

Neutralizing antibodies, which can bind to the surface of virus particles and induce a preventive effect by neutralizing viral infectivity, increased 8.5 times after administration of the vaccine twice, and serum conversion was observed in more than 79% of the subjects.

The safety evaluation was conducted by 23,745 people who participated in 4 clinical trials.The average age of the analysis target was 41.8 years, 35.8% of those with underlying diseases such as obesity, cardiovascular system, and respiratory system, and 8.9% of the elderly over 65 years old. Included.

The predicted adverse events after vaccination, such as pain at the injection site, occurred in about 87% of the vaccine group and about 74% of the control group, and the symptoms were mostly mild to moderate, and the incidence was generally reduced in the second dose compared to the first dose.

In addition, about 38% of the vaccine group and 28% of the control group were unpredicted after the vaccine was administered, and the symptoms of the adverse events were mostly mild to moderate.

In addition, during the clinical trial period, serious adverse events were reported in 0.7% of the vaccine group and 0.8% of the control group, and 1 case of fever and 1 case of transverse myelitis in the vaccine group that cannot be excluded from the vaccine administration. There were no adverse reactions such as anaphylaxis reaction and exacerbation of corona symptoms that may appear as hypersensitivity reactions after vaccine administration.

This is an evaluation of effectiveness and safety for the elderly over 65 years of age. As a result of evaluating the preventive effect and safety of the elderly over 65 years of age, one corona19 occurred in the elderly vaccine-administered group and the control group, and there were no hospitalizations or serious diseases in both the control group and the vaccine group.

In the immunogenicity evaluation, binding antibodies and neutralizing antibodies were produced in the elderly who received the vaccine, and there was no significant difference in the seroconversion rate compared to the adult group.

In terms of safety, the incidence of predicted or unpredicted adverse events was similar or low compared to the adult group, and no significant drug-related adverse events occurred.

Consultation content and results. First, the dose of the vaccine. During clinical trials, some subjects asked whether the application dose of two standard doses was appropriate, considering that the second standard dose was administered after the first low dose, ie, one-half the standard dose.

The verification advisory group determined that it is appropriate to administer twice as a standard dose whose effectiveness has been confirmed in the planned clinical trial, considering the following points.

The consideration was that the planned dose in the clinical trial was the standard dose, and the prophylactic effect was higher in the standard dose at the first dose at the low dose and the standard dose, and the dose interval between the low dose group and the standard dose group, and the age of the subject were different. Simple comparison was not appropriate and the number of subjects in the low-dose group was small, so the comparison between groups was limited.

The interval between doses of the vaccine. We asked whether 4 to 12 weeks were appropriate, considering that the wider the interval between the first and second vaccines tends to show a higher prophylactic effect.

The verification advisory group commented that the requested dosing interval was appropriate based on the fact that the effect lasted up to 12 weeks after the first vaccination and that the preventive effect was confirmed when administered for 4 to 12 weeks in major clinical trials conducted in Brazil.

However, it was recommended that it is necessary to present specific guidelines for administration intervals after approval, after consulting with experts, when using in the clinical field.

It is effective and safe for the elderly over 65 years old. Considering the limited data on the elderly population, we consulted on whether vaccination was appropriate for the elderly.

Many experts believe that clinical trial plans are designed to confirm efficacy and safety in subjects 18 years of age or older. Prevention effect was confirmed in all subjects including 65 years of age or older. The immune response after vaccine administration is similar to that of adults. Considering the good safety profile, it was the opinion that administration to the elderly could not be excluded just because the number of elderly people among the participants was small.

According to the opinion of a few experts, the preventive effect was not proven due to lack of data on the high-risk elderly, and the serum conversion rate from immunogenicity was not different from that of adults, but the antibody value was lower than that of adults under 65 years of age. As the correlation was not established, there were opinions that it is desirable to reflect in the approval matters after additional results such as clinical trials.

Safety and others. Regarding adverse events that occurred in clinical trials, the Validation Advisory Board believes that the safety profile, that is, some trends in safety, is considered acceptable in clinical trials, but that the occurrence of nervous system-related adverse events including transverse myelitis requires close monitoring after approval. Presented.

In addition, the verification advisory group advised that it is not recommended to administer the vaccine during pregnancy in relation to the administration of pregnant women, and it was suggested that lactating mothers describe in permission matters, that is, precautions for use, that it was unknown whether the vaccine was secreted into breast milk .