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Clinical Trial
. 2020 Dec 31;383(27):2603-2615.
doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10.

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack  1 , Stephen J Thomas  1 , Nicholas Kitchin  1 , Judith Absalon  1 , Alejandra Gurtman  1 , Stephen Lockhart  1 , John L Perez  1 , Gonzalo Pérez Marc  1 , Edson D Moreira  1 , Cristiano Zerbini  1 , Ruth Bailey  1 , Kena A Swanson  1 , Satrajit Roychoudhury  1 , Kenneth Koury  1 , Ping Li  1 , Warren V Kalina  1 , David Cooper  1 , Robert W Frenck Jr  1 , Laura L Hammitt  1 , Özlem Türeci  1 , Haylene Nell  1 , Axel Schaefer  1 , Serhat Ünal  1 , Dina B Tresnan  1 , Susan Mather  1 , Philip R Dormitzer  1 , Uğur Şahin  1 , Kathrin U Jansen  1 , William C Gruber  1 ; C4591001 Clinical Trial Group
Collaborators, Affiliations
Clinical Trial

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack et al. N Engl J Med. .

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.

Methods: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we 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 RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.

Results: A total of 43,548 participants underwent randomization, 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 characterized 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.

Conclusions: 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. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

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Figures

Figure 1
Figure 1. Enrollment and Randomization.
The diagram represents all enrolled participants through November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.
Figure 2
Figure 2. Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 or Placebo, According to Age Group.
Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel A. Pain at the injection site was assessed according to the following scale: mild, does not interfere with activity; moderate, interferes with activity; severe, prevents daily activity; and grade 4, emergency department visit or hospitalization. Redness and swelling were measured according to the following scale: mild, 2.0 to 5.0 cm in diameter; moderate, >5.0 to 10.0 cm in diameter; severe, >10.0 cm in diameter; and grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated in the key; medication use was not graded. Additional scales were as follows: fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain (mild: does not interfere with activity; moderate: some interference with activity; or severe: prevents daily activity), vomiting (mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; or severe: requires intravenous hydration), and diarrhea (mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; or severe: 6 or more loose stools in 24 hours); grade 4 for all events indicated an emergency department visit or hospitalization. 𝙸 bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.
Figure 3
Figure 3. Efficacy of BNT162b2 against Covid-19 after the First Dose.
Shown is the cumulative incidence of Covid-19 after the first dose (modified intention-to-treat population). Each symbol represents Covid-19 cases starting on a given day; filled symbols represent severe Covid-19 cases. Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for Covid-19 case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for vaccine efficacy (VE) is derived according to the Clopper–Pearson method.
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