A phase 3 trial yesterday in the New England Journal of Medicine (NEJM) finds that the Novavax COVID-19 vaccine is 90.4% effective against infection and 100% effective against moderate to severe illness, bringing yet another vaccine one step closer to approval.
Novavax is a new adjuvanted, recombinant spike protein nanoparticle vaccine that has proven effective against COVID-19 infection in the United Kingdom and South Africa. This was the first such trial in North America.
The study, led by Novavax researchers in Gaithersburg, Maryland, involved 29,949 adults who received the Novavax vaccine at 113 sites in the United States and 6 in Mexico from Dec 27, 2020, to Feb 18, 2021, before the emergence of the highly transmissible Delta (B1617.2) and Omicron (B.1.1.529) variants. Participants were followed until Apr 19, 2021.
The researchers randomly assigned participants in a 2:1 ratio to receive either two doses of Novavax vaccine or a saline placebo 21 days apart. Median participant age was 47 years, and 11.8% were 65 years and older, 75.9% were White, 21.5% were Hispanic, 11.0% were Black, and 47.3% had at least one underlying medical condition.
Of 29,582 participants who received at least one dose, 19,714 received vaccine and 9,868 received placebo.
Efficacy against earlier variants was 92.6%
In the full-analysis population, 21.2 cases per 1,000 person-years occurred in the Novavax group, compared with 51.9 per 1,000 in the placebo group.
Over 3 months, 77 participants who received at least one dose tested positive for COVID-19, 14 of them vaccinees and 63 placebo recipients, for a vaccine efficacy of 90.4%. Rates of infection were 3.3 per 1,000 person-years among those given at least one dose, versus 34.0 cases per 1,000 among placebo recipients.
Ten moderate and four severe COVID-19 infections occurred, all in the placebo group, for a vaccine efficacy against moderate to severe illness of 100%. Vaccine efficacy against infection among high-risk recipients was 91.0%. Hispanic participants were the only demographic group in which Novavax effectiveness was lower, at 67.3%.
The rate of new COVID-19 infections among Novavax recipients was higher in the first 42 days of follow-up than during the rest of the study period. As a result, the incidence of new infections fell among the vaccinated while increasing in the placebo group.
Similar vaccine effectiveness was seen in the full-analysis population when observation started 7 days after the second dose, with 85 COVID-19 infections (16 in the Novavax group and 69 in the placebo group). Incidence was 3.7 cases per 1,000 person-years and 34.6 cases per 1000, respectively, for a vaccine effectiveness of 89.3%.
Most sequenced viral genomes (79% of 61) were variants of concern or interest, most of them Alpha (B117) and other variants of concern (89% of 35). Vaccine effectiveness against any variant of concern or interest was 92.6%.
Few severe vaccine-related adverse events
Adverse effects, which were mostly mild to moderate and short-term, occurred more often among Novavax recipients than in the placebo group and were most common after the second dose (58.0% and 21.1%, respectively, after the first dose and 78.9% and 21.7%, respectively, after the second dose).
Systemic adverse events occurred in 47.7% of vaccinees and 40.0% in the placebo group after the first dose and 69.5% and 35.9% after the second. Severe adverse events were reported in 1.1% of Novavax recipients and less than 1% of placebo recipients after the first dose and 6.7% and less than 1%, respectively, after the second.
The study authors said that Novavax's ability to be stored for up to 6 months at normal refrigerator temperatures make it well-suited for international deployment.
"The efficacy of NVX-CoV2373 [Novavax] in preventing moderate-to-severe COVID-19 as well as any symptomatic COVID-19 in people at high risk for acquisition and complications of COVID-19 will make this vaccine a valuable tool in controlling the pandemic and its most serious health and economic consequences," they concluded.
In a related audio interview, NEJM Editor-in-Chief Eric Rubin, MD, PhD, said that, in the context of great global COVID-19 vaccine need, it's good to have another effective vaccine candidate like Novavax. "For now, I think which vaccine is superior is less important than which vaccines work and are available," he said.
"I think we really need to get those vaccines out there, even if there are subtle differences among them in how effective they are or what side effects they have."
