Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

Abstract

Background: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population.

Methods: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline.

Results: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups.

Conclusions: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).

Figure 1. Enrollment and Outcomes.

The full analysis set (safety population) included all the participants who had undergone randomization and received at least one dose of the NVX-CoV2373 vaccine or placebo, regardless of protocol violations or missing data. The primary end point was analyzed in the per-protocol population, which included participants who were seronegative at baseline, had received both doses of trial vaccine or placebo, had no major protocol deviations affecting the primary end point, and had no confirmed cases of symptomatic coronavirus disease 2019 (Covid-19) during the period from the first dose until 6 days after the second dose.

Figure 2. Solicited Local and Systemic Adverse Events.

The percentage of participants who had solicited local and systemic adverse events during the 7 days after each injection of the NVX-CoV2373 vaccine or placebo is plotted according to the maximum toxicity grade (mild, moderate, severe, or potentially life-threatening). Data are not included for the 400 trial participants who were also enrolled in the seasonal influenza vaccine substudy.

Figure 3. Kaplan–Meier Plots of Efficacy of the NVX-CoV2373 Vaccine against Symptomatic Covid-19.

Shown is the cumulative incidence of symptomatic Covid-19 in the per-protocol population (Panel A), the intention-to-treat population (Panel B), and the per-protocol population with the B.1.1.7 variant (Panel C). The timing of surveillance for symptomatic Covid-19 began after the first dose in the intention-to-treat population and at least 7 days after the administration of the second dose in the per-protocol population (i.e., on day 28) through approximately the first 3 months of follow-up.

Figure 4. Vaccine Efficacy of NVX-CoV2373 in Specific Subgroups.

Shown is the efficacy of the NVX-CoV2373 vaccine in preventing Covid-19 in various subgroups within the per-protocol population. Vaccine efficacy and 95% confidence intervals were derived with the use of Poisson regression with robust error variance. In the intention-to-treat population, vaccine efficacy was assessed after the administration of the first dose of vaccine or placebo. Participants who identified themselves as being non-White or belonging to multiple races were pooled in a category of “other” race to ensure that the subpopulations would be large enough for meaningful analyses. Data regarding coexisting conditions were based on the definition used by the Centers for Disease Control and Prevention for persons who are at increased risk for Covid-19.