Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

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 .)

The Safety of Anti-SARS-CoV-2 Vaccines: Vigilance Is Still Required

“…Importantly, polyethylene glycol, which is present in adenoviral-vector-based and mRNA vaccines, was identified as the ingredient responsible for most of these allergic reactions [ 1 ]. The NVX-CoV2373 vaccine from Novavax is devoid of polyethylene glycol, and no anaphylactic reactions were reported with this product [ 2 ]. Therefore, patients hypersensitive to polyethylene glycol can be safely immunized with the NVX-CoV2373 vaccine.…”

“…It is very unlikely that existing pharmacovigilance programs will be able to establish the risk of SARS-CoV-2 vaccination revealing or accelerating the course of lymphomas or other immunological diseases. As previously mentioned, we should remember that the thrombotic thrombocytopenia rarely induced by the ChAdOx1nCoV-19 vaccine was not primarily identified by pharmacovigilance systems but came to light because of a few isolated case reports, followed by a series of mechanistic studies [ 2 ]. Likewise, studies specifically designed and powered to investigate possible rare TFH-related reactions suggested by well-documented case reports and a sound scientific rationale might allow detrimental consequences of SARS-CoV-2 vaccination to be prevented in patients with certain lymphoproliferative or autoimmune diseases.…”

New drug: SARS-CoV-2 rS (NVX-CoV-2373) vaccine for prevention of COVID-19

“…All cases of COVID-19 in the vaccinated group were mild. 4 In the phase III trials, adverse reactions were more frequent following vaccination than in the placebo groups. Reactions were more common after the second dose, in younger people and in participants who received simultaneous influenza vaccine.…”

“…Reactions were more common after the second dose, in younger people and in participants who received simultaneous influenza vaccine. [2][3][4] The most frequent reactions were injection-site tenderness (75%) or pain (62%). Systemic adverse effects reported in the trials included headache, arthralgia, myalgia and fatigue.…”

“…The adverse reactions lasted for an average of one or two days. 2,4 Uncommon adverse events include hypertension and myocarditis. As anaphylaxis is a potential adverse reaction, patients should be observed for at least 15 minutes after being vaccinated.…”