NVX-CoV2705 is indicated for individuals aged 12 to 64 years with an underlying condition that poses high risk for severe COVID-19 outcomes.
FDA approves NVX-CoV2705 COVID-19 vaccine | Image credit: Contemporary Pediatrics
On May 19, 2025, the FDA approved a biologics license application (BLA) for the NVX-CoV2705 (Nuvaxovid; Novavax) COVID-19 vaccine, a recombinant protein-based, non-mRNA COVID-19 vaccine, the only of its kind in the United States, according to a press release from Novavax.1
The indication is for individuals aged 12 to 64 years with at least one underlying condition, such as asthma, cancer, diabetes, obesity, or smoking, which puts them at high risk for severe outcomes of COVID-19, along with all adults aged 65 years and older.
The approval triggered a $175 million milestone payment under the collaboration and license agreement between Novavax and Sanofi signed in 2024. According to the announcement, Sanofi is leading on commercialization efforts starting this year and Novavax is eligible to receive ongoing tiered royalties from stand-alone COVID-19 vaccine sales for all future vaccination seasons.
The BLA was approved based on pivotal phase 3 data demonstrating safety and efficacy for NVX-CoV2705. Among a phase 3 trial featuring 2247 adolescents aged 12 to 17 years (NCT04611802), NVX-CoV2373 was safe, immunogenic, and efficacious in preventing COVID-19. Neutralizing antibody responses were noninferior compared to young adults aged 18 to 25 years.1,2
In the trial, 1487 patients received the vaccine while 745 patients received placebo. Participants had a mean age of 13.4 years, and 52.2% were male. Of the total participants, 16.1% had a previous SARS-CoV-2 infection at baseline. Following vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7).2
A vaccine efficacy of 79.5% was yielded after 20 mild cases of COVID-19 occurred after a median of 64 days of follow-up. This included cases among 6 NVX-CoV2373 recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), and 14 among placebo patients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years). For the Delta variant, the only viral variant identified by sequencing (n = 11), vaccine efficacy was 82% (95% CI, 32.4%-95.2%).
Reactogenicity was mostly mild to moderate and transient and there were no safety concerns identified by investigators, who stated, "The vaccine is expected to increase uptake in adolescents, more than 22% of whom have not yet received a full vaccination regimen with mRNA vaccines," in a JAMA Network Open publication of the study data. "A favorable safety profile, convenient storage and transportation requirements, and induction of broad, cross-reactive immune responses with the potential to provide protection against new variants suggest that NVX-CoV2373 offers an important choice for vaccination of younger individuals in the fight against the current COVID-19 pandemic worldwide," they concluded.
Approval data was also based on another phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico among adults aged 18 years and older, who had not had SARS-CoV-2 infection. In this trial (NCT04611802), participants (n = 29,949) were randomly assigned 2:1 to receive 2 doses of NVX-CoV2373 or placebo 21 days apart, with a primary objective to determine vaccine efficacy against reverse-transcriptase–polymerase-chain-reaction–confirmed COVID-19 occurring at least 7 days after the second dose.3
"Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7)," wrote the investigative team in a December 15, 2021, New England Journal of Medicine publication. "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," they wrote. The study authors concluded the vaccine was safe and effective in preventing COVID-19 and that most breakthrough cases were caused by contemporary variant strains.
"Today's approval solidifies a pathway for Americans aged 65 and older and those aged 12 through 64 with an underlying condition that puts them at high risk for severe outcomes from COVID-19 to have access to a protein-based, non-mRNA COVID-19 vaccine," said John C. Jacobs, president, CEO, Novavax, in a statement. "Market research and US CDC statistics indicate that older individuals and those with underlying conditions are the populations most likely to seek out COVID-19 vaccination seasonally. This significant milestone demonstrates our commitment to these populations and is a significant step towards the availability of our protein-based vaccine option."1
The FDA has requested a post-marketing commitment to conduct a phase 4 prospective, randomized, double-blinded, placebo-controlled efficacy and safety trial among individuals aged 50 to 64 without high-risk conditions for severe COVID-19.
References:
1. US FDA approves BLA for Novavax's COVID-19 vaccine. Novavax, Inc. Press release. May 19, 2025. Accessed May 19, 2025. https://www.prnewswire.com/news-releases/us-fda-approves-bla-for-novavaxs-covid-19-vaccine-302458535.html
2. Áñez G, Dunkle LM, Gay CL, et al. Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(4):e239135. doi:10.1001/jamanetworkopen.2023.9135
3. Dunkle LM, Kotloff KL, Gay CL, et al. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N Engl J Med. 2021; 386(6). doi:10.1056/NEJMoa2116185
