On May 30, 2025, the U.S. Food and Drug Administration (FDA) licensed mNEXSPIKE (mRNA-1283), a newly developed mRNA COVID-19 biologic for individuals who have previously received any COVID shots and are either 65 years of age or older, or between 12 and 64 years old with at least one underlying medical condition that increases their risk of severe illness from COVID, as defined by the U.S. Centers for Disease Control and Prevention (CDC).1
In a press release, Moderna announced that its updated COVID shot is expected to be available in the United States ahead of the 2025–2026 respiratory virus season, which begins in the fall of 2025. The company is revising its original mRNA shot formulation to target the LP.8.1 variant of the SARS-CoV-2 virus, and submitted an application to the FDA in May 2025 seeking approval for the new version.2
The FDA approved mNEXSPIKE based on results from a Phase 3 clinical trial involving approximately 11,400 participants ages 12 and older. The study compared the new shot to Moderna’s original mRNA shot, Spikevax. Participants received either a lower dose of mNEXSPIKE or a standard dose of the original vaccine. The goal was to determine whether the updated version was at least as effective.
Results showed that mNEXSPIKE had about 9 percent greater effectiveness overall, and more than a 13 percent greater effectiveness in adults aged 65 and older. The results also showed that the safety profile was similar to the original shot, with fewer local reactions such as arm pain, and comparable general side effects including fatigue, headache, and muscle aches.3
Risks and Side Effects Associated With mNEXSPIKE
According to Moderna’s press release, some individuals have experienced severe allergic reactions to mNEXSPIKE. These reactions usually begin within minutes to an hour after receiving the shot. As a precaution, healthcare providers should typically ask patients to remain on site for observation shortly after administrating the shot. Symptoms of a severe allergic reaction can include difficulty breathing, swelling of the face or throat, a fast heartbeat, a widespread rash, dizziness, or weakness.4
There have also been reported cases of myocarditis and pericarditis following mRNA COVID-19 shots. These cases have occurred most often in males between the ages of 12 and 24. Moderna urged individuals to seek immediate care if they develop chest pain, shortness of breath, or a fast or irregular heartbeat, especially within two weeks of receiving the mNEXSPIKE shot.5
In clinical trials, participants commonly reported side effects at the injection site, such as pain, swelling, redness, or tenderness, as well as swelling of lymph nodes in the same arm. Other general side effects included fatigue, headache, muscle or joint pain, chills, nausea, vomiting, and fever.6
FDA Requires Moderna to Conduct Post-Marketing Safety Studies
The FDA has directed Moderna to carry out the following post-marketing studies on mSPIKEVAX:7
* Study mRNA-1283-P901
This study will use commercial and Medicare claims databases to assess the occurrence of myocarditis and pericarditis following mNEXSPIKE administration. Final report submission is due on Sept. 30, 2029.
* Study mRNA-1283-P904
This study will use administrative claims and health system medical records to evaluate long-term health effects of myocarditis in individuals who received mNEXSPIKE, compared to those who developed myocarditis without having received a COVID-19 shot. Participants will be followed for at least five years. Final report submission is due on Mar. 31, 2034.
In addition, Moderna is required to adhere to post-marketing commitments subject to reporting requirements under section 506b:
* An observational cohort study using administrative claims data to assess maternal and infant outcomes following exposure to mNEXSPIKE during pregnancy (Study mRNA-1283-P902).Final Report Submission is due on Dec. 15, 2032.
* A Phase 4, Randomized, Observer Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of mRNA-1283 Variant-containing Formulation in Adults 50 to 64 Years of Age Without High-Risk Conditions for Severe COVID-19. (Study mRNA-21283-XXXX). Final Report Submission is due on Jan. 31, 2027.
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Click here to view References:1 Moderna. Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE. May. 31, 2025.
2 Ibid.
3 Ibid.
4 Ibid.
5 Ibid.
6 Ibid.
7 U.S. Food and Drug Administration. Approval Letter mNEXSPIKE. May 30, 2025.
