Moderna's mRNA-1010 Flu Vaccine Proves Superior Efficacy in Pivotal Late-Stage Trial

Moderna’s investigational mRNA-based seasonal influenza vaccine, mRNA-1010, showed superior efficacy compared to a licensed standard-dose flu vaccine in adults aged 50 and older, according to topline results from the pivotal phase 3 P304 trial.

The study demonstrated a relative vaccine efficacy (rVE) of 26.6% (95% CI, 16.7%-35.4%) against laboratory-confirmed influenza illness in the overall population. In adults aged 65 years and older, the rVE was 27.4%. These findings meet the trial’s most stringent superiority criterion, Moderna said in the June 30, 2025 announcement.1

rVE was also strong against individual influenza strains: A/H1N1 (29.6%), A/H3N2 (22.2%), and B/Victoria (29.1%). P304 researchers also reported the mRAA-1010 efficacy was consistent across age groups, comorbidities, and prior vaccination status.1

“Today's strong phase 3 efficacy results are a significant milestone in our effort to reduce the burden of influenza in older adults. The severity of this past flu season underscores the need for more effective vaccines,” Moderna CEO Stéphane Bancel, said in the announcement. “An mRNA-based flu vaccine has the potential advantage to more precisely match circulating strains, support rapid response in a future influenza pandemic, and pave the way for COVID-19 combination vaccines.”1

In a previous phase 3 study, published in February in the journal Vaccine, the mRNA-1010's seroconversion rates and geometric mean titer ratios had been shown superior against all strains included in the vaccine compared to both high-dose and standard-dose licensed seasonal influenza vaccine.2

The P304 trial enrolled 40,805 participants across 11 countries. The randomized, observer-blind, active-controlled study included a median follow-up time of 6 months. The safety and tolerability of mRNA-1010 was similar to that seen in prior studies, with mostly mild solicited adverse reactions (AEs). Injection site pain was the most frequent local reaction; fatigue, headache, and myalgia were the most common systemic symptoms. No meaningful differences were observed in the rates of unsolicited adverse events, serious AEs or AEs of special interest.1

According to the CDC, seasonal flu-related hospitalizations and outpatient visits reached a 15-year high during the 2024-2025 season.3 More than 600,000 Americans were hospitalized due to flu-related illness last year, leading to substantial direct and indirect costs, as well as widespread disruption to daily life and work.4

mRNA-1010 is a vaccine candidate that encodes for hemagglutinin (HA) glycoproteins of the 4 influenza strains recommended by the World Health Organization for the prevention of influenza, including influenza A/H1N1, A/H3N2, and influenza B/Yamagata- and B/Victoria-lineages, Moderna stated. HA is a major influenza surface glycoprotein that is considered an important target to generate broad protection against influenza and is the primary target of currently available influenza vaccines.1

The company plans to present full data at an upcoming medical meeting and will pursue regulatory engagement and submission, according to the statement.1

References

1. Moderna announces positive phase 3 results for seasonal influenza vaccine. News release. Moderna. June 30, 2025. Accessed June 30, 2025. https://investors.modernatx.com/news/news-details/2025/Moderna-Announces-Positive-Phase-3-Results-for-Seasonal-Influenza-Vaccine/default.aspx

2. A phase 3 randomized safety and immunogenicity trial of mRNA-1010 seasonal influenza vaccine in adults. Vaccine. 2025;19:50:126847. doi: 10.1016/j.vaccine.2025.126847

3. Weekly US influenza surveillance report: key updates for week 6, ending February 8, 2025. FluView. Centers for Disease Control and Prevention. February 14, 1015. Accessed June 30, 2025. https://www.cdc.gov/fluview/surveillance/2025-week-06.html

4. Preliminary estimated flu disease burden 2024-2025 flu season. Flu Burden. Centers for Disease Control and Prevention. May 9, 20225. Accessed June 30, 2025. https://www.cdc.gov/flu-burden/php/data-vis/2024-2025.html