The trivalent formulation of mRNA-1010 contained mRNAs encoding surface hemagglutinin antigens of three WHO-recommended 2024-2025 cell- or recombinant-based influenza strains. The 37.5mcg intramuscular dose comprised 12.5mcg of each strain.The preferred comparator was a standard dose trivalent vaccine, but a quadrivalent, high dose or adjuvanted vaccine was used depending on availability and local requirement.
The primary measure of efficacy was a first episode of protocol-defined, RT-PCR assay confirmed influenza illness caused by any influenza A or B strain beginning at least 14 days after the injection, through the end of the influenza season.Active surveillance included monitoring twice-weekly e-diary prompts to report respiratory symptoms.Safety and reactogenicity were assessed from adverse events from e-diary entry and unsolicited reports.
There were 968 confirmed cases of influenza across the three circulating strains.The investigators reported that the mRNA-1010 met pre-specified criterion of higher-level superiority relative to the comparator, with approximately 27% fewer cases of illness over the median 181 day follow-up (2.0% of the mRNA-1010 group vs 2.8% of the comparator group). An exploratory analysis found that medically attended influenza-associated outcomes across all health care settings occurred in 80 recipients of mRNA-1010 and 120 receiving the comparator.
What You Need to Know
Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 9-0 that the benefits of mRNA-1010 outweigh its risks for preventing seasonal influenza in adults aged 50 years and older, supporting the vaccine ahead of the FDA’s August 5 PDUFA decision.
In a trial of more than 40,000 adults aged 50 and older, mRNA-1010 reduced laboratory-confirmed influenza cases by approximately 27% compared with licensed influenza vaccines, with 2.0% of recipients developing influenza versus 2.8% in the comparator group.
Recipients of mRNA-1010 experienced higher rates of injection-site pain, fatigue, headache, and myalgia than those receiving comparator vaccines, although serious adverse event rates were low and similar between groups (2.2% vs 1.9%), highlighting a benefit-risk tradeoff that clinicians and patients may need to consider.
The mRNA-100 was, however, associated with more frequent adverse reactions than the comparator: injection-site pain in 65.8% vs 29.8%, fatigue in 45.1% vs 20.3%, headache in 37.8% vs 18.0%, and myalgia in 35.4% vs 11.6%. Serious adverse events were reported in 2.2% of recipients of mRNA-1010 vs 1.9% with the comparator vaccine.
The investigators noted that while mRNA-1010 demonstrated superior efficacy and that serious adverse events were infrequent and similar in the two groups, the greater frequency of solicited adverse reactions with mRNA-1010 will warrant consideration in selecting between agents.
The more common adverse events with the investigational vaccine, Leroux-Roels and colleagues indicate, "suggests a need for balancing assessment of temporary vaccine-induced reactogenicity events with the magnitude of protection against influenza."
References
1. Moderna. News Release. Moderna announces FDA advisory committee votes unanimously in favor of the benefit-risk profile of mRNA-1010, an investigational seasonal influenza vaccine. 2026, June 18. https://feeds.issuerdirect.com/news-release.html?newsid=5170330895753287&symbol=MRNA . Accessed June 18, 2026.
2. Moderna. News Release. Moderna Receives Refusal-to-File Letter from the US Food and Drug Administration for its investigational seasonal influenza vaccine, mRNA-1010.
4. Leroux-Roels I, Huang G, Ferguson M, et al. Efficacy and safety of an mRNA seasonal influenza vaccine in adults. N Engl J Med. 2026; 394:1803-1814,
