Key Takeaways
- FDA grants full approval to Novavax’s COVID-19 vaccine, Nuvaxovid, for individuals aged 65 and older, as well as those aged 12–64 with underlying conditions that increase their risk for severe COVID-19, marking its first full US approval following Emergency Use Authorization in 2022.
- Approval was supported by the Phase III PREVENT-19 trial, which showed 90.4% efficacy against symptomatic COVID-19 and 100% efficacy against moderate to severe disease, with a favorable safety profile.
- Novavax and Sanofi are preparing for fall 2025 commercialization, with Sanofi leading US sales and Novavax eligible for royalties. Both companies are also evaluating a newly requested Phase IV trial in lower-risk adults aged 50–64 years.
The FDA has granted full approval to Novavax’s COVID-19 vaccine, Nuvaxovid, for individuals aged 65 years and older as well as for those between 12 and 64 years of age with at least one underlying medical condition associated with an increased risk of severe COVID-19. This marks the first full US approval for the protein-based vaccine, which had been available under Emergency Use Authorization since July 2022.
How Will the FDA Approval of Novavax’s Vaccine Reshape Its US Commercial Strategy?
The approval activates a $175 million milestone payment to Novavax from its commercialization partner Sanofi, under the terms of a licensing agreement signed in May 2024. Sanofi is expected to lead future commercialization efforts in the United States, while Novavax will be eligible for tiered royalties on US sales.1
"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 press release.
Clinical Trial Results Demonstrate High Efficacy and Safety
Approval was based on data from the pivotal Phase III PREVENT-19 trial, a randomized, placebo-controlled, observer-blinded study evaluating the efficacy, safety, and immunogenicity of Nuvaxovid with Matrix-M adjuvant in 29,960 adults aged 18 years and older across the United States and Mexico. The primary endpoint was the prevention of PCR-confirmed symptomatic COVID-19 beginning at least seven days after the second dose among participants who were seronegative at baseline. Secondary endpoints included prevention of moderate and severe disease.
Results demonstrated an overall efficacy of 90.4% against symptomatic COVID-19 and 100% efficacy against moderate to severe disease. Additionally, the vaccine demonstrated a favorable safety and tolerability profile, with minimal serious adverse events (AEs). The most common AEs included headache; nausea; vomiting; myalgia; arthralgia; injection site tenderness; fatigue; and malaise.2
Temporary Clinical Hold Resolved Following Safety Review
In October 2024, the FDA put the vaccine on a clinical hold, citing a report of a serious AE involving motor neuropathy in a participant from a prior Phase II trial. A month later, the hold was lifted after the AE was reclassified as amyotrophic lateral sclerosis, which was deemed to not be associated with the trial.3
FDA Requests Additional Safety Study for Broader Population
In conjunction with the approval, the FDA has requested a new Phase IV trial to assess the vaccine’s safety and efficacy in adults between 50 and 64 years of age who do not have high-risk conditions for severe COVID-19. Novavax is working with Sanofi to assess funding and execution of this study, which supplements ongoing post marketing requirements shared by other vaccine manufacturers.1
CDC Trends and Market Outlook Support Targeted Vaccination Strategy
According to the Centers for Disease Control and Prevention (CDC), there was a 2.9% positivity rate for COVID during the week ending May 10, 2025, with no reported change from the previous week. However, emergency department visits were down 19.5% from the previous week.4
"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,” continued Jacobs, in the press release. “This significant milestone demonstrates our commitment to these populations and is a significant step towards availability of our protein-based vaccine option."
Next Steps for Novavax: Updated Vaccine Rollout in Fall 2025
Looking ahead, Novavax plans to begin commercial delivery of its updated 2025–2026 COVID-19 vaccine formula in the United States this fall, pending the upcoming strain recommendation from the FDA’s Vaccines and Related Biological Products Advisory Committee, scheduled to meet on May 22.1
References
1. U.S. FDA Approves BLA for Novavax's COVID-19 Vaccine. Novavax. May 19, 2025. Accessed May 20, 2025. https://ir.novavax.com/press-releases/2025-05-19-U-S-FDA-Approves-BLA-for-Novavaxs-COVID-19-Vaccine
2. Novavax Announces Positive Results of COVID-19 Vaccine in Pediatric Population of PREVENT-19 Phase 3 Clinical Trial. Novavax. February 10, 2022. Accessed May 20, 2025. https://ir.novavax.com/press-releases/2022-02-10-Novavax-Announces-Positive-Results-of-COVID-19-Vaccine-in-Pediatric-Population-of-PREVENT-19-Phase-3-Clinical-Trial
3. FDA Lifts Clinical Hold on Novavax’s Trials for COVID-19-Influenza Combination, Standalone Influenza Vaccines. PharmExec. November 11, 2024. Accessed May 20, 2025. https://www.pharmexec.com/view/fda-lifts-clinical-hold-novavax-trials-covid-19-influenza-combination-standalone-influenza-vaccines
4. United States COVID-19 Deaths, Emergency Department (ED) Visits, and Test Positivity by Geographic Area. CDC. Accessed May 20, 2025. https://covid.cdc.gov/covid-data-tracker/#maps_percent-covid-deaths
