Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.1.7 Variant

Toback, S.; Heath, P. T.; Galiza, E. P.; Baxter, D.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D. R.; Clark, R.; Cosgrove, C.; Galloway, J.; Goodman, A. L.; Heer, A.; Higham, A.; Iyengar, S.; Jamal, A.; Jeanes, C.; Kalra, P. A.; Kyriakidou, C.; McAuley, D. F.; Meyrick, A.; Minassian, A. M.; Minton, J.; Moore, P.; Munsoor, I.; Nicholls, H.; Osanlou, O.; Packham, J.; Pretswell, C.; San Francisco Ramos, A.; Saralaya, D.; Sheridan, R. P.; Smith, R.; Soiza, R. L.; Swift, P. A.; Thomson, E. C.; Turner, J.; Viljoen, M. E.; Albert, G.; Cho, I.; Dubovsky, F.; Glenn, G.; Rivers, J.; Robertson, A.

Background: Covid-19 vaccines are urgently needed, especially against emerging variants. NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 rS) nanoparticle vaccine containing trimeric full-length SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant. Methods: A phase 3, randomized, observer-blinded, placebo-controlled trial was conducted in adults 18-84 years old who received two intramuscular 5-mcg doses, 21 days apart, of NVX-CoV2373 or placebo (1:1) across 33 sites in the United Kingdom. The primary efficacy endpoint was virologically confirmed symptomatic Covid-19 with onset 7 days after second vaccination in serologically negative participants. Results: A total of 15,187 participants were randomized, of whom 7569 received NVX-CoV2373 and 7570 received placebo; 27.2% were 65 years or older, 44.7% had comorbidities and 4.2% had baseline serological evidence of SARS-CoV-2. There were 10 cases of Covid-19 among NVX-CoV2373 recipients and 96 cases among placebo recipients, with symptom onset at least 7 days after second vaccination; NVX-CoV2373 was 89.7% (95% confidence interval, 80.2 to 94.6) effective in preventing Covid-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8 to 99.5) and 86.3% (71.3 to 93.5) against the prototype strain and B.1.1.7 variant, respectively. Vaccine efficacy was similar across subgroups, including participants with comorbidities and those [≥]65 years old. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. Conclusion: A two-dose regimen of NVX-CoV2373 conferred 89.7% protection against a blend of prototype and variant Covid-19, demonstrated high efficacy against the B.1.1.7 variant, and had a reassuring safety profile.