Safety of the NVX-CoV2373 COVID-19 vaccine in randomized placebo-controlled clinical trials

Background: NVX-CoV2373 (NuvaxovidTM or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/ -booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7- 90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged & GE; 18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials. Methods: All participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years). Findings: Pooled data from 49,950 participants (NVX-CoV2373, n = 30,058; placebo, n = 19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76 %/systemic, 70 %) than placebo recipients (local, 29 %/systemic, 47 %), and were mostly of mild-to -moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipi-ents (local, 6.28 %/systemic, 11.36 %) than placebo recipients (local, 0.48 %/systemic, 3.58 %). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (SAEs: 0.91 %, deaths: 0.07 %) and placebo recipients (SAEs: 1.0 %, deaths: 0.06 %). Interpretation: To date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults. Funding: Supported by Novavax, Inc. & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).