Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
Lisa M Dunkle, Karen L Kotloff, Cynthia L Gay, Germán Áñez, Jeffrey M Adelglass, Alejandro Q Barrat Hernández, Wayne L Harper, Daniel M Duncanson, Monica A McArthur, Diana F Florescu, R Scott McClelland, Veronica Garcia-Fragoso, Robert A Riesenberg, David B Musante, David L Fried, Beth E Safirstein, Mark McKenzie, Robert J Jeanfreau, Jeffrey K Kingsley, Jeffrey A Henderson, Dakotah C Lane, Guillermo M Ruíz-Palacios, Lawrence Corey, Kathleen M Neuzil, Robert W Coombs, Alex L Greninger, Julia Hutter, Julie A Ake, Katherine Smith, Wayne Woo, Iksung Cho, Gregory M Glenn, Filip Dubovsky, 2019nCoV-301 Study Group
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.).
Copyright © 2021 Massachusetts Medical Society.
Figures
References
- Slaoui M, Hepburn M. Developing safe and effective Covid vaccines — Operation Warp Speed’s strategy and approach. N Engl J Med 2020;383:1701-1703.
- Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-416.
- Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.
- Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021;397:671-681.
- Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.
- SARS-CoV-2 variant classifications and definitions. Atlanta: Centers for Disease Control and Prevention, 2021. ().
- Harvey WT, Carabelli AM, Jackson B, et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol 2021;19:409-424.
- Krause PR, Fleming TR, Longini IM, et al. SARS-CoV-2 variants and vaccines. N Engl J Med 2021;385:179-186.
- Holder J. Tracking coronavirus vaccinations around the world. New York Times. 2021. ().
- Keech C, Albert G, Cho I, et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med 2020;383:2320-2332.
- Formica N, Mallory R, Albert G, et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: a phase 2 randomized placebo-controlled trial. PLoS Med 2021;18(10):e1003769-e1003769.
- Shinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N Engl J Med 2021;384:1899-1909.
- Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of the NVX-CoV2373 Covid-19 vaccine. N Engl J Med 2021;385:1172-1183.
- Nexstrain. Genomic epidemiology of novel coronavirus — global subsampling. 2021. ().
- Guidance for industry: development and licensure of vaccines to prevent COVID-19. Silver Spring, MD: Food and Drug Administration, June 2020. ().
- Corey L, Mascola JR, Fauci AS, Collins FS. A strategic approach to COVID-19 vaccine R&D. Science 2020;368:948-950.
- Joffe S, Babiker A, Ellenberg SS, et al. Data and safety monitoring of COVID-19 vaccine clinical trials. J Infect Dis 2021. May 19 (Epub ahead of print).
- People with certain medical conditions. Atlanta: Centers for Disease Control and Prevention, 2021. ().
- Center for Biologics Evaluation and Research. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. Silver Spring, MD: Food and Drug Administration, September 2007. ().
- Coronavirus (COVID-19) update. Silver Spring, MD: Food and Drug Administration, July 13, 2021. ().
- Myocarditis and pericarditis after mRNA COVID-19 vaccination. Atlanta: Centers for Disease Control and Prevention, 2021. ().
- Hunter PR. Thrombosis after covid-19 vaccination. BMJ 2021;373:n958-n958.
- Falsey AR, Sobieszczyk ME, Hirsch I, et al. Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 vaccine. N Engl J Med 2021;385:2348-2360.
- Follmann D, Fintzi J, Fay MP, et al. A deferred-vaccination design to assess durability of COVID-19 vaccine effect after the placebo group is vaccinated. Ann Intern Med 2021;174:1118-1125.
Source: PubMed