Pfizer/BioNTech COVID-19 vaccine meets primary endpoints
Pfizer and BioNTech have completed the final efficacy analysis in the ongoing Phase 3 study of their mRNA-based COVID-19 vaccine candidate, BNT162b2, concluding that it met all of the study’s primary efficacy endpoints.
Analysis of the data indicates a vaccine efficacy rate of 95% in participants without prior SARS-CoV-2 infection (first primary objective) and also in participants with and without prior SARS-CoV-2 infection (second primary objective), in each case measured from seven days after the second dose. This is even higher than the 90% efficacy reported by the companies after initial data analysis just last week.
The first primary objective analysis is based on 170 cases of COVID-19, of which 162 cases of COVID-19 were observed in the placebo group versus eight cases in the BNT162b2 group. Efficacy was consistent across age, gender, race and ethnicity demographics. The observed efficacy in adults over 65 years of age was over 94%. There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2 vaccinated group. The Data Monitoring Committee for the study has not reported any serious safety concerns related to the vaccine, with most solicited adverse events resolving shortly after vaccination.
The companies have also announced that the safety milestone required by the US FDA for Emergency Use Authorization (EUA) has been achieved. Pfizer and BioNTech plan to submit a request within days to the FDA for an EUA based on the totality of safety and efficacy data collected to date, as well as manufacturing data relating to the quality and consistency of the vaccine. These data also will be submitted to other regulatory agencies around the world.
“We are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30 µg dose, underscoring the power of BNT162 in providing early protection,” said Dr Ugur, CEO and co-founder of BioNTech.
“Our objective from the very beginning was to design and develop a vaccine that would generate rapid and potent protection against COVID-19 with a benign tolerability profile across all ages. We believe we have achieved this with our vaccine candidate BNT162b2 in all age groups studied so far and look forward to sharing further details with the regulatory authorities.”
Pfizer and BioNTech plan to submit the efficacy and safety data from the study for peer review in a scientific journal once analysis of the data is completed. The trial will continue to collect efficacy and safety data in participants for an additional two years.
Meanwhile, the University of Oxford’s vaccine against SARS-CoV-2 has shown similar safety and immunogenicity results in healthy older adults (aged 56 years and over) to those seen in adults aged 18–55 years, according to early-stage data published in The Lancet — a particularly promising result given that the immune system gradually deteriorates with age.
The Phase 2 trial saw 560 healthy participants (160 aged 18–55 years, 160 aged 56–69 years and 240 aged 70 or over) split into 10 groups, where they received either the ChAdOx1 nCoV-19 vaccine at a low or standard dose, or a control vaccine. Participants aged over 55 years were also split into groups and either given a single dose of vaccine or two doses 28 days apart.
The vaccine was found to induce antibodies against the SARS-CoV-2 spike protein and receptor binding domain 28 days after a single low or standard dose across all age groups. Following the booster dose of the vaccine, antibody levels increased at day 56 of the trial, irrespective of dose or participant age. The same was seen with levels of neutralising antibodies at day 42, two weeks after the booster vaccine dose. By 14 days after the boost dose, 208 of 209 participants (selected from participants of all ages and doses) had neutralising antibody responses. T cell responses against the SARS-CoV-2 spike protein meanwhile peaked 14 days after first vaccination, regardless of age and low or standard vaccine dose.
Adverse reactions to the ChAdOx1 nCoV-19 vaccine were mild (the most common effects were injection-site pain and tenderness, fatigue, headache, feverishness and muscle pain), but more common than seen with the control vaccine. Adverse effects were less common in older adults than in younger adults and similar levels of local symptoms were seen after the first and booster doses of the COVID-19 vaccine in older adults, while there were few systemic symptoms following the booster dose.
A Phase 2 trial found that the vaccine causes few side effects and induces immune responses in both parts of the immune system in all age groups and at low and standard dose — provoking a T cell response within 14 days of the first dose of vaccination and an antibody response within 28 days of the booster dose of vaccination.
The authors note some limitations to their study, including that the participants in the oldest age group had an average age of 73–74 years and few underlying health conditions. The authors also note that almost all participants of all ages were white and non-smokers, and may not be representative of the general population. People from a range of backgrounds, countries and ethnicities are being included in the Phase 3 trial of this vaccine, as are older adults with underlying health conditions.
“The WHO has outlined a number of critical factors for COVID-19 vaccines, including that they must be targeted at the most at-risk groups including older adults,” said study co-author Professor Sarah Gilbert. “They must also be safe, effective in preventing disease and/or transmission and provide at least six months of protection for people frequently exposed to the virus — such as healthcare workers.
“Our new study answers some of these questions about protecting older adults, but questions remain about effectiveness and length of protection, and we need to confirm our results in older adults with underlying conditions to ensure that our vaccine protects those most at risk of severe COVID-19 disease.”
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