mRNA-1083 elicited higher immune responses against influenza virus and SARS-CoV-2 than licensed flu and COVID vaccines in adults 50 years and older.

RT’s Three Key Takeaways:

  1. Primary Endpoints Met: Moderna’s phase 3 trial for the mRNA-1083 combination vaccine met its primary endpoints, demonstrating non-inferior immune responses compared to the co-administered, licensed comparator vaccines for both influenza and COVID-19.
  2. Immune Response: The mRNA-1083 vaccine elicited statistically significantly higher immune responses against three influenza strains (H1N1, H3N2, and B/Victoria) and the SARS-CoV-2 variant Omicron XBB.1.5 in both age cohorts (50-64 years and 65 years and older) compared to the licensed flu and COVID-19 vaccines.
  3. Safety and Tolerability: The combination vaccine showed an acceptable safety and tolerability profile, with most adverse reactions being mild (grade 1 or 2) and similar to those observed with the comparator vaccines. The most common reactions were injection site pain, fatigue, myalgia, and headache.

Moderna Inc announced that its phase 3 trial of mRNA-1083, an investigational combination vaccine against influenza and COVID-19, has met its primary endpoints, eliciting a higher immune response than the licensed comparator vaccines used in the trial.

mRNA-1083 comprises components of mRNA-1010, Moderna’s vaccine candidate for seasonal influenza, and mRNA-1283, Moderna’s next-generation COVID-19 vaccine candidate. Each investigational vaccine has independently demonstrated positive phase 3 clinical trial results.

The ongoing phase 3 clinical trial is a randomized, observer-blind, active control study evaluating the safety, reactogenicity, and immunogenicity of mRNA-1083 in two independent age group cohorts of approximately 4,000 adults each. 

One cohort, consisting of adults 65 years and older, compared mRNA-1083 to co-administered Fluzone HD, an enhanced influenza vaccine, and Spikevax, Moderna’s currently licensed COVID-19 vaccine. The other cohort of adults 50 to 64 years of age compared mRNA-1083 to co-administered, Fluarix, a standard dose influenza vaccine, and Spikevax.

The immune responses from a single dose of mRNA-1083 were found to be non-inferior versus the co-administered, routinely recommended, licensed comparators. In both age cohorts, mRNA-1083 also elicited statistically significantly higher immune responses against three influenza virus strains (H1N1, H3N2, and B/Victoria) and against SARS-CoV-2. 

Geometric Mean Ratios and Efficacy

In the 65 years and older cohort, overall Geometric Mean Ratios (GMRs) of the mRNA-1083 group compared to the Fluzone HD group for the influenza strains were 1.155 (95% CI: 1.094, 1.220) for A/H1N1, 1.063 (95% CI: 1.007, 1.122) for A/H3N2 and 1.118 (95% CI: 1.070, 1.167) for B/Victoria. The GMR of mRNA-1083 compared to Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.641 (95% CI: 1.526, 1.765).

In the 50 to 64 years of age cohort the GMRs of the mRNA-1083 group compared to the Fluarix group for the influenza virus strains were 1.414 (95% CI: 1.333, 1.500) for A/H1N1, 1.380 (95% CI: 1.310, 1.454) for A/H3N2, and 1.216 (95% CI: 1.163, 1.270) for B/Victoria. The GMR of mRNA-1083 compared to Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.308 (95% CI: 1.219, 1.404).

Safety and Tolerability

Immunogenicity was also tested against the B/Yamagata strain of influenza and mRNA-1083 met non-inferiority criteria in both age cohorts. Due to the disappearance of the B/Yamagata lineage from circulation, the World Health Organization has recommended a trivalent influenza vaccine composition without B/Yamagata for 2024/2025 vaccines.

mRNA-1083 showed an acceptable tolerability and safety profile. The majority of solicited adverse reactions were grade 1 or 2 in severity and consistent with the licensed vaccines used in the trial. The most commonly solicited adverse reactions were injection site pain, fatigue, myalgia, and headache.

CEO Comments and Future Plans

“Combination vaccines have the potential to reduce the burden of respiratory viruses on health systems and pharmacies, as well as offer people more convenient vaccination options that could improve compliance and provide stronger protection from seasonal illnesses,” says Stéphane Bancel, chief executive officer of Moderna, in a release. “Moderna is the only company with a positive phase 3 flu and COVID combination vaccine. Building on the momentum of positive phase 3 data across our respiratory portfolio, we continue to address significant unmet medical needs and advance public health.”

Moderna plans to present the phase 3 clinical data for mRNA-1083 at an upcoming medical conference as well as submit it for publication. The company will engage with regulators on next steps.

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