Image Credit: © Dr_Microbe – stock.adobe.com
Key takeaways
- Large-Scale, Multinational Trial Design: The P304 study enrolled over 40,000 participants across 11 countries, showcasing the complexity and operational scale required for global Phase III vaccine trials.
- Diverse Stratification and Efficacy Subsets: Consistent efficacy across age groups, risk profiles, and prior vaccination history reinforces the need for robust subgroup planning and analytics in trial protocols.
- Streamlined Safety Monitoring: Mild and predictable safety signals align with prior data, emphasizing the importance of continuous SAR tracking and harmonization across study sites for mRNA platforms.
Moderna has shared positive results from P304, a Phase III clinical trial (NCT06602024) of mRNA-1010 and its efficacy against the influenza virus. When compared to a licensed standard-dose seasonal influenza vaccine in adults aged 50 years and older, mRNA-1010 demonstrated a relative vaccine efficacy (rVE) of 26.6% (95% CI; 16.7%, 35.4%). This mark met the study protocol’s most stringent superiority criterion.1
In a press release, Stéphane Bancel, chief executive officer of Moderna, said: “Today’s strong Phase III 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. 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.”
Consistent efficacy across influenza strains and patient groups
In addition to mRNA-1010’s strong success in rVE within the overall study population, the vaccine candidate demonstrated:
- Similar efficacy across each influenza strain contained in the vaccine, including A/H1N1 (rVE=29.6%), A/H3N2 (rVE=22.2%), and the B/Victoria lineages (rVE=29.1%).
- A consistently strong rVE point estimate across age groups, risk factors, and previous influenza vaccination status.
- An rVE of 27.4% in patients aged 65 years and older.
Trial design highlights global scope and participant diversity
- The P304 trial is a randomized, observer-blind, active-controlled, case-driven, pivotal efficacy, immunogenicity, and safety study.
- Across 11 countries, 40,805 adults aged 50 years and older were enrolled.
- Study participants were randomly assigned to receive either a single dose of mRNA-1010 or a standard-dose licensed comparator, with a median follow-up of six months.
Safety profile remains consistent with prior data
In terms of safety and tolerability, data from mRNA-1010 in P304 were consistent with previously reported results from another Phase III study, IGNITE P303 (NCT05827978). The majority of solicited adverse reactions (SARs) were mild.
- The most common local SAR was injection site pain.
- The most common systemic SARs reported were fatigue, headache, and myalgia.
- Data showed there we no significant differences between the study groups in the rates of unsolicited adverse events, serious adverse events, or adverse events of special interest.
IGNITE P303 supports robust immune response in older adults
The IGNITE P303 trial evaluated the immunogenicity and safety of mRNA-1010 across three parts: adults aged ≥18 years (Part A), 18–64 years (Part B), and ≥ 65 years (Part C). The findings from the trial, published in Vaccine, demonstrated that a single dose of mRNA-1010 achieved an acceptable safety profile and created strong immune responses against influenza A and B strains.2
“The robust immunogenicity observed in adults aged ≥65 years could represent a meaningful benefit for this vulnerable population and a Phase III efficacy trial is in progress,” the study authors wrote. “Overall, these findings support the potential of mRNA-1010 as an enhanced seasonal influenza vaccine candidate with the benefits of the mRNA platform.”
Regulatory update: BLA resubmission pending efficacy data
Earlier in May, Moderna announced it had voluntarily withdrawn its Biologics License Application (BLA) for mRNA-1083, a flu/COVID combination vaccine candidate for adults aged 50 years and older. This action came in response to a new framework proposed by the FDA, calling for increased oversight in COVID-19 vaccine trials.3
In an official press release from the time, Moderna stated, “The Company plans to resubmit the BLA later this year, after vaccine efficacy data from the ongoing Phase III trial of its investigational seasonal influenza vaccine, mRNA-1010, are available. Moderna continues to expect interim data from the mRNA-1010 trial to be available this summer.”
The new framework around COVID-19 vaccine research, regarding those with no risk factors for severe COVID-19, calls for randomized, controlled trial data evaluating clinical outcomes before BLAs can be granted.
References
1. Moderna Announces Positive Phase 3 Results for Seasonal Influenza Vaccine. News release. Moderna. June 30, 2025. Accessed July 10, 2025. https://investors.modernatx.com/news/news-details/2025/Moderna-Announces-Positive-Phase-3-Results-for-Seasonal-Influenza-Vaccine/default.aspx
2. Soens, M. et al. A phase 3 randomized safety and immunogenicity trial of mRNA-1010 seasonal influenza vaccine in adults. Vaccine. Volume 50. March 19, 2025. Accessed July 10, 2025. https://doi.org/10.1016/j.vaccine.2025.126847
3. FDA Outlines Updated Requirement for Placebo-Controlled Trials in Vaccine Research. Applied Clinical Trials. May 21, 2025. Accessed July 10, 2025. https://www.appliedclinicaltrialsonline.com/view/fda-outlines-updated-requirement-placebo-controlled-trials-vaccine-research