Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

  • N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577.
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
Affiliations
  • 1. From Fundacion INFANT (F.P.P.) and iTrials-Hospital Militar Central (G.P.M.), Buenos Aires; State University of New York, Upstate Medical University, Syracuse (S.J.T.), and Vaccine Research and Development, Pfizer, Pearl River (J.A., A.G., K.A.S., K.K., W.V.K., D.C., P.R.D., K.U.J., W.C.G.) - both in New York; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); Vaccine Research and Development (J.L.P., P.L.) and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Bahia (E.D.M.), and Centro Paulista de Investigação Clinica, São Paulo (C.Z.) - both in Brazil; Global Product Development, Pfizer, Peapack, NJ (S.R.); Cincinnati Children's Hospital, Cincinnati (R.W.F.); Johns Hopkins Bloomberg School of Public Health, Baltimore (L.L.H.); BioNTech, Mainz (ÖT., U.Ş.), and Medizentrum Essen Borbeck, Essen (A.S.) - both in Germany; Tiervlei Trial Centre, Karl Bremer Hospital, Cape Town, South Africa (H.N.); Hacettepe University, Ankara, Turkey (S.Ü.); and Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Groton, CT (D.B.T.).
PMID: 33301246 DOI: 10.1056/NEJMoa2034577
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.).