Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase

El Sahly, Hana M.; Baden, Lindsey R.; Essink, Brandon; Doblecki-Lewis, Susanne; Martin, Judith M.; Anderson, Evan J.; Campbell, Thomas B.; Clark, Jesse; Jackson, Lisa A.; Fichtenbaum, Carl J.; Zervos, Marcus; Rankin, Bruce; Eder, Frank; Feldman, Gregory; Kennelly, Christina; Han-Conrad, Laurie; Levin, Michael; Neuzil, Kathleen M.; Corey, Lawrence; Gilbert, Peter; Janes, Holly; Follmann, Dean; Marovich, Mary; Polakowski, Laura; Mascola, John R.; Ledgerwood, Julie E.; Graham, Barney S.; August, Allison; Clouting, Heather; Deng, Weiping; Han, Shu; Leav, Brett; Manzo, Deb; Pajon, Rolando; Schödel, Florian; Tomassini, Joanne E.; Zhou, Honghong; Miller, Jacqueline

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)