Randomized Controlled Trial
Study population and setting
This was a Phase 2/3 placebo controlled, observer blinded study in healthy people aged 16 years and older. The mRNA-based vaccine (BNT162b2) or placebo was administered in 2 doses at least 21 days apart. Study participants were split 1:1 between the vaccine and placebo arms. A total of 43,548 participants were enrolled in the United States, Argentina, Brazil, Turkey, South Africa, and Germany. Participants were monitored for adverse events from the time of injection and for COVID-19 disease (reporting at least one symptom with a positive RNA test) from seven days after the second dose. This report does not include efficacy for asymptomatic infections since these data are still being analyzed.
Summary of Main Findings
This paper reported on interim safety and efficacy data from Phase 2/3 of an ongoing global Phase 1/2/3 trial. BNT162b2 is a lipid nanoparticle formulated, nucleoside-modified RNA (modRNA) vaccine encoding the SARS-CoV-2 Spike protein. This interim report indicates that the BNT162b2 vaccine is 95% efficacious. As of this report, 8 out of 21,720 participants in the vaccine arm and 162 out of 21,728 in the placebo arm had confirmed symptomatic cases of COVID-19. This level of efficacy was similar across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. However, the study was not powered to demonstrate statistical significance between these subgroups. After the first dose but before the second dose, 39 COVID-19 cases were observed in the BNT162b2 group and 82 cases in the placebo group indicating 52% efficacy after only a single dose of BNT162b2. Of 10 observed severe cases, 9 were in the placebo and 1 was in the vaccinated group. While these numbers are too low to draw definitive conclusions, the trends suggest the vaccine will also protect against severe cases of COVID-19. The safety profile of BNT162b2 (assessed for at least 2 months up to 14 weeks post second dose) was acceptable. Of the 43,252 participants in the study, serious adverse events were rare and similar in the vaccine and placebo groups (0.6% and 0.5%, respectively). Most common adverse reactions were mild-to-moderate pain, redness, swelling at the injection site, fatigue, and headache. Reported local reactions did not increase upon the second inoculation, however systemic reactogenicity (mostly fevers and headaches) did increase in both frequency and severity. While deaths occurred in both the vaccine (n=2) and placebo (n=4) groups, none of these deaths were attributable to vaccination or were due to COVID-19.
This study far exceeded the predefined metrics for success (30% efficacy) to demonstrate that BNT162b2 is a safe and highly efficacious vaccine against COVID-19. Subgroups with multiple risk factors were included in this study (35% obese, 21% had at least one coexisting condition, 42% were over 55 years of age) suggesting that the vaccine will be effective in the most at risk individuals.
This was an interim analysis of a Phase 2/3 clinical trial. As such, there are still outstanding data to be collected and analyzed. Data demonstrating the durability of the immune response and protection against asymptomatic infection remain to be analyzed. The study population here was also predominantly white (83%), therefore, more data in more diverse populations will be necessary to fully know if any differences in efficacy exist. As is typical in vaccine development, this study did not include children, pregnant women or immunocompromised individuals. Future studies in these populations are planned. The safety data reported here does not include 196 participants infected with HIV. These data were collected and will be analyzed separately, per the protocol.
This study demonstrated that the BNT162b2 vaccine is safe and efficacious against COVID-19. Importantly, it demonstrated that mRNA vaccines are a viable and promising approach as a new vaccine technology. Additionally, it showed the feasibility of the continuous phase 1/2/3 trial design, which could be beneficial for development of future vaccines.
This review was posted on: 14 December 2020