Randomised double-blinded placebo-controlled trial (Orange)
SARS-CoV-2 infection and resulting COVID-19 have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial recently published in the New England Journal of Medicine, the authors randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified ribonucleic acid (RNA) vaccine that encodes a prefusion stabilised, membrane-anchored SARS-CoV-2 full-length spike protein. The primary endpoints were efficacy of the vaccine against laboratory-confirmed COVID-19 and safety. A total of 43,548 participants underwent randomisation, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of COVID-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing COVID-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe COVID-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterised by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. The authors concluded that a two-dose regimen of BNT162b2 conferred 95% protection against COVID-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines.