COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Primary Prevention Dunkle LM, Kotloff KL, Gay CL, et al. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N Engl J Med. 2021 Dec 15. doi: 10.1056/NEJMoa2116185.
PICO Terms
adult (P) adverse reactions; safety (O) alpha; B.1.1.7; variant of concern; VOC (P) any infection (O) beta; B.1.351; variant of concern; VOC (P) gamma; P.1; variant of concern; VOC (P) genome sequencing (O) healthy (P) moderate disease (O) Novavax vaccine; NVX-CoV2373; protein subunit (I/C) placebo (I/C) reactogenicity (O) severe disease (O) vaccine efficacy (O)
Demographic Information
Geriatric Population
60 years to <70 years 70 years to <80 years 80+ years
Gender
Female Male
Race
African American Alaska Native Asian Black Hispanic Indigenous Latino Multiracial Native American, American Indian Native Hawaiian or other Pacific Islander
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.).

Ratings
Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Infectious Disease
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Not relevant to clinicians in countries where this is not approved.

General Internal Medicine-Primary Care(US) rater

Pfizer and Moderna MRNA vaccines dominate the US market, with some folks still getting the Johnson & Johnson vaccine, although there are concerns about the safety of J/J. Unclear whether this Novavax could be useful in the US for patients opposed to MRNA vaccines but with Omicron taking over, this Novavax vaccine may become less useful.