Key Takeaways
- FDA Approves Moderna’s mNEXSPIKE for High-Risk Populations: Moderna’s next-generation COVID-19 vaccine, mNEXSPIKE (mRNA-1283), has received FDA approval for adults aged 65 years and older and individuals aged 12–64 years with CDC-defined risk factors for severe illness.
- Phase III Trial Shows Higher Efficacy Than Spikevax: In the Phase III NextCOVE trial, mNEXSPIKE demonstrated non-inferiority to Spikevax and delivered up to 13.5% higher relative vaccine efficacy in adults aged 65 years and older.
- Streamlined Formulation Eases Provider Burden: mNEXSPIKE offers improved storage, extended shelf life, and comes in a pre-filled syringe format to enhance convenience for healthcare providers and expand vaccine accessibility.
The FDA has approved mNEXSPIKE (mRNA-1283), Moderna’s next-generation COVID-19 vaccine, for use in adults aged 65 years and older, as well as in individuals aged 12 to 64 years who have at least one risk factor for severe disease as defined by the Centers for Disease Control and Prevention (CDC). This marks the third approved product from Moderna and represents a key advancement in the company’s respiratory vaccine portfolio.
What Makes Moderna’s mNEXSPIKE Different from Previous COVID-19 Vaccines?
According to the company, approval was supported by data from the Phase III NextCOVE trial, which demonstrated that mNEXSPIKE demonstrated non-inferiority to Spikevax (mRNA-1273) in preventing COVID-19. Additionally, the new vaccine showed higher relative vaccine efficacy compared to its predecessor.1
"The FDA approval of our third product, mNEXSPIKE, adds an important new tool to help protect people at high risk of severe disease from COVID-19," said Stéphane Bancel, CEO, Moderna, in a press release. "COVID-19 remains a serious public health threat, with more than 47,000 Americans dying from the virus last year alone. We appreciate the FDA's timely review and thank the entire Moderna team for their hard work and continued commitment to public health."
Phase III Data Highlight Higher Efficacy in Older Adults
The randomized, observer-blind, active-controlled NextCOVE trial enrolled approximately 11,400 participants aged 12 years and older across the United States, United Kingdom, and Canada. Participants received either a 10 μg dose of mNEXSPIKE or a 50 μg dose of Spikevax. The study’s primary objective was to assess vaccine efficacy beginning 14 days after administration of the mNEXSPIKE dose, compared with the established mRNA-1273 formulation.1,2
Study findings revealed that mNEXSPIKE delivered a 9.3% higher rVE in individuals aged 12 years and older, and a 13.5% higher rVE in adults aged 65 years and older.
Safety Profile and Administration Advantages
In addition to its efficacy, mNEXSPIKE demonstrated a favorable safety profile, with fewer reported adverse events (AEs) than Spikevax. Commonly reported AEs included injection site pain, fatigue, headache, and myalgia.1 Moderna also highlighted operational advantages, noting that improvements in storage, shelf life, and the use of a pre-filled syringe could help reduce the burden on healthcare providers during vaccination efforts.
Dose Flexibility and Phase I Immunogenicity Results
Earlier interim data from a Phase I trial further supported the potential of mNEXSPIKE. In that study, the vaccine elicited comparable immune responses to Spikevax across 10 μg, 30 μg, and 100 μg dose levels, all administered on a two-dose schedule spaced 28 days apart. Notably, the 10 μg dose demonstrated the most favorable tolerability profile while generating strong neutralizing and binding antibody responses, suggesting that a lower-dose, two-dose regimen may provide similar protection to that of mRNA-1273, according to the trial investigators.2
COVID-19 Remains a Public Health Priority
Meanwhile, public health data underscore the continuing relevance of COVID-19 vaccination. For the week ending May 24, 2025, CDC data indicated a 2.7% test positivity rate for COVID-19 in the United States, a slight decline of 0.1% from the prior week. Emergency department visits remained stable at 0.3%, hospitalizations dropped slightly to 0.9 per 100,000 individuals, and the COVID-related death rate held steady at 0.4%.3
Looking Ahead to the 2025–2026 Respiratory Virus Season
Detailed results from the NextCOVE trial were first announced in March during Moderna’s Vaccines Day event.
"We are excited to announce our fourth infectious disease vaccine program with positive Phase III data, further validating our robust mRNA platform," said Bancel, in a March press release. “mRNA-1283 is a critical component of our combination vaccine against flu and COVID-19, mRNA-1083, and this milestone gives us confidence in our ability to bring this much needed vaccine to market."2
References
1. Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE. Moderna. May 31, 2025. Accessed June 2, 2025. https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S--FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx
2. Phase III NextCOVE Trial Data Show Efficacy of Moderna's Next-Generation COVID-19 Vaccine. Applied Clinical Trials. March 26, 2025. Accessed June 2, 2025. https://www.appliedclinicaltrialsonline.com/view/phase-iii-nextcove-trial-data-show-efficacy-of-moderna-s-next-generation-covid-19-vaccine
3. COVID Data Tracker. CDC. Accessed June 2, 2025. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
