TY - JOUR
T1 - Efficacy and safety of NVX-COV2373 in adults in the United States and Mexico
AU - 2019nCoV-301 Study Group
AU - Dunkle, Lisa M.
AU - Kotloff, Karen L.
AU - Gay, Cynthia L.
AU - Áñez, Germán
AU - Adelglass, Jeffrey M.
AU - Barrat Hernández, Alejandro Q.
AU - Harper, Wayne L.
AU - Duncanson, Daniel M.
AU - McArthur, Monica A.
AU - Florescu, Diana F.
AU - McClelland, R. Scott
AU - Garcia-Fragoso, Veronica
AU - Riesenberg, Robert A.
AU - Musante, David B.
AU - Fried, David L.
AU - Safirstein, Beth E.
AU - McKenzie, Mark
AU - Jeanfreau, Robert J.
AU - Kingsley, Jeffrey K.
AU - Henderson, Jeffrey A.
AU - Lane, Dakotah C.
AU - Ruíz-Palacios, Guillermo M.
AU - Corey, Lawrence
AU - Neuzil, Kathleen M.
AU - Coombs, Robert W.
AU - Greninger, Alex L.
AU - Hutter, Julia
AU - Ake, Julie A.
AU - Smith, Katherine
AU - Woo, Wayne
AU - Cho, Iksung
AU - Glenn, Gregory M.
AU - Dubovsky, Filip
N1 - Publisher Copyright:
© 2021 Massachusetts Medical Society
PY - 2022/2/10
Y1 - 2022/2/10
N2 - BACKGROUND NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains.
AB - BACKGROUND NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains.
UR - http://www.scopus.com/inward/record.url?scp=85123980637&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2116185
DO - 10.1056/NEJMoa2116185
M3 - Article
C2 - 34910859
AN - SCOPUS:85123980637
SN - 0028-4793
VL - 386
SP - 531
EP - 543
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -