tetano
Editor, Senior Moderator
N Engl J Med
. 2021 Dec 15.
doi: 10.1056/NEJMoa2116185. Online ahead of print.
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
Lisa M Dunkle[SUP] 1 [/SUP], Karen L Kotloff[SUP] 1 [/SUP], Cynthia L Gay[SUP] 1 [/SUP], Germán Áñez[SUP] 1 [/SUP], Jeffrey M Adelglass[SUP] 1 [/SUP], Alejandro Q Barrat Hernández[SUP] 1 [/SUP], Wayne L Harper[SUP] 1 [/SUP], Daniel M Duncanson[SUP] 1 [/SUP], Monica A McArthur[SUP] 1 [/SUP], Diana F Florescu[SUP] 1 [/SUP], R Scott McClelland[SUP] 1 [/SUP], Veronica Garcia-Fragoso[SUP] 1 [/SUP], Robert A Riesenberg[SUP] 1 [/SUP], David B Musante[SUP] 1 [/SUP], David L Fried[SUP] 1 [/SUP], Beth E Safirstein[SUP] 1 [/SUP], Mark McKenzie[SUP] 1 [/SUP], Robert J Jeanfreau[SUP] 1 [/SUP], Jeffrey K Kingsley[SUP] 1 [/SUP], Jeffrey A Henderson[SUP] 1 [/SUP], Dakotah C Lane[SUP] 1 [/SUP], Guillermo M Ruíz-Palacios[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 [/SUP], Kathleen M Neuzil[SUP] 1 [/SUP], Robert W Coombs[SUP] 1 [/SUP], Alex L Greninger[SUP] 1 [/SUP], Julia Hutter[SUP] 1 [/SUP], Julie A Ake[SUP] 1 [/SUP], Katherine Smith[SUP] 1 [/SUP], Wayne Woo[SUP] 1 [/SUP], Iksung Cho[SUP] 1 [/SUP], Gregory M Glenn[SUP] 1 [/SUP], Filip Dubovsky[SUP] 1 [/SUP], 2019nCoV-301 Study Group
Affiliations
Abstract
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. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).
. 2021 Dec 15.
doi: 10.1056/NEJMoa2116185. Online ahead of print.
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
Lisa M Dunkle[SUP] 1 [/SUP], Karen L Kotloff[SUP] 1 [/SUP], Cynthia L Gay[SUP] 1 [/SUP], Germán Áñez[SUP] 1 [/SUP], Jeffrey M Adelglass[SUP] 1 [/SUP], Alejandro Q Barrat Hernández[SUP] 1 [/SUP], Wayne L Harper[SUP] 1 [/SUP], Daniel M Duncanson[SUP] 1 [/SUP], Monica A McArthur[SUP] 1 [/SUP], Diana F Florescu[SUP] 1 [/SUP], R Scott McClelland[SUP] 1 [/SUP], Veronica Garcia-Fragoso[SUP] 1 [/SUP], Robert A Riesenberg[SUP] 1 [/SUP], David B Musante[SUP] 1 [/SUP], David L Fried[SUP] 1 [/SUP], Beth E Safirstein[SUP] 1 [/SUP], Mark McKenzie[SUP] 1 [/SUP], Robert J Jeanfreau[SUP] 1 [/SUP], Jeffrey K Kingsley[SUP] 1 [/SUP], Jeffrey A Henderson[SUP] 1 [/SUP], Dakotah C Lane[SUP] 1 [/SUP], Guillermo M Ruíz-Palacios[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 [/SUP], Kathleen M Neuzil[SUP] 1 [/SUP], Robert W Coombs[SUP] 1 [/SUP], Alex L Greninger[SUP] 1 [/SUP], Julia Hutter[SUP] 1 [/SUP], Julie A Ake[SUP] 1 [/SUP], Katherine Smith[SUP] 1 [/SUP], Wayne Woo[SUP] 1 [/SUP], Iksung Cho[SUP] 1 [/SUP], Gregory M Glenn[SUP] 1 [/SUP], Filip Dubovsky[SUP] 1 [/SUP], 2019nCoV-301 Study Group
Affiliations
- PMID: 34910859
- DOI: 10.1056/NEJMoa2116185
Abstract
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. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).